DNA Mismatch Repair Deficiency and Immune Checkpoint Inhibitors in Gastrointestinal Cancers. Ruiz-Bañobre Juan,Goel Ajay Gastroenterology In the recent few years, significant efforts have been undertaken for the development of different immunotherapeutic approaches against cancer. In this context, immune checkpoint inhibitors (ICIs), a novel class of immunotherapeutic drugs with the potential to unleash the immune system, have emerged as authentic game-changers for managing patients with various cancers, including gastrointestinal malignancies. Although the majority of gastrointestinal cancers are generally considered poorly immunogenic, basic research findings and data from clinical trials have proven that subset(s) of patients with various digestive tract cancers are highly responsive to ICI-based therapy. In this context, a better understanding on the role of various DNA repair pathway alterations, especially the evidence supporting the significant importance of DNA mismatch repair deficiencies and the efficacy of the anti-programmed cell death 1 drugs, have led to US Food and Drug Administration approval of 2 anti-programmed cell death 1 antibodies (pembrolizumab and nivolumab) for the treatment of patients with microsatellite instability. This review aims to provide a comprehensive and up-to-date summary for the role of DNA mismatch repair deficiency in cancer, and its importance in the development of ICI therapy. In addition, we provide insights into the spectrum of various genetic alterations underlying ICI resistance, together with the important influence that the tumor microenvironment plays in mediating the therapeutic response to this new class of drugs. Finally, we provide a comprehensive yet succinct glimpse into the most exciting preclinical discoveries and ongoing clinical trials in the field, highlighting bench-to-beside translational impact of this exciting area of research. 10.1053/j.gastro.2018.11.071
    Developments in the study of gastrointestinal microbiome disorders affected by FGF19 in the occurrence and development of colorectal neoplasms. Peng Meichang,Zheng Qiaowen,Liu Peiqi,Liang Xinyun,Zhang Min,Wang Yan,Zhao Yi Journal of cellular physiology Colorectal neoplasms are a type of malignant digestive system tumor that has become the third-highest morbidity tumor in China and the fourth leading cause of cancer-related death worldwide. The role of the gastrointestinal (GI) microbiome in bile acid metabolism, inflammation, and insulin resistance and its strong correlation with the occurrence and development of colorectal neoplasms have gradually led to it becoming a target area of tumor research. Fibroblast growth factor (FGF) 19 is a hormone that is secreted in mainly the ileum and can regulate bile acid biosynthesis, improve inflammation, and regulate insulin resistance. The relationship of the GI microbiome, FGF19 and its carcinogenic activities in colorectal neoplasms enticed us to search for potential targets and research ideas for the clinical diagnosis and treatment of colorectal neoplasms. 10.1002/jcp.29322
    Research progress on prevention and treatment of glucolipid metabolic disease with integrated traditional Chinese and Western medicine. Guo Jiao Chinese journal of integrative medicine Hyperlipidemia, type 2 diabetes mellitus, nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients. In addition, these diseases are closely related in pathophysiological settings. However, increasing of the disease incidence, lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattern of the single disease, single target therapy, that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine (WM). On the basis of the combination of the advantages of integrated Chinese medicine (CM) and WM, with unified understanding of such diseases, the new concept of glucolipid metabolic disease (GLMD) is introduced. In this new concept, disorders in glucose and lipid metabolism are recognized as the key trigger and major driving force for the progress of GLMD. The key points of pathology included dysfunction of neuronal-endocrine-immune system, insulin resistance, oxidative stress, inflammation and intestinal flora imbalance. In the core pathogenic perspective of CM, it can be explained as "Gan (Liver) Shi Shu Xie" (dysfunction of Gan in metabolism and emotion regulation) that will lead to the occurence/production of endogenous dampness and phlegm, blood stasis and turbid. This leads to the new concept of "Liver-based regulatory system for metabolic homeostasis" to be introduced further. The comprehensive prevention and control strategy "Tiao Gan Qi Shu Hua Zhuo" (modulating Gan, trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness). Its representative formula Fufang Zhenzhu Tiaozhi Capsule () is innovated under such rationales. Comment for some commonly-used CM GLMD therapeutic drugs was presented. High-level evidence-based and epidemiological and mechanism studies should be carried out to further interpret and explain of the scientific connotation of GLMD. 10.1007/s11655-017-2811-3
    The Metabolic Profiling of Isorhamnetin-3-O-Neohesperidoside Produced by Human Intestinal Flora Employing UPLC-Q-TOF/MS. Du Le-Yue,Zhao Min,Tao Jin-Hua,Qian Da-Wei,Jiang Shu,Shang Er-Xin,Guo Jian-Ming,Liu Pei,Su Shu-Lan,Duan Jin-Ao Journal of chromatographic science Isorhamnetin-3-O-neohesperidoside is the major active substance of Puhuang, a traditional herb medicine widely used in clinical practice to tackle many chronic diseases. However, little is known about the interactions between this ingredient and intestinal flora. In this study, ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry together with automated data analysis software (Metabolynx™) was used for analysis of the metabolic profile of isorhamnetin-3-O-neohesperidoside by the isolated human intestinal bacteria. The parent and three metabolites isorhamnetin-3-O-glucoside, isorhamnetin and quercetin were detected and identified based on the characteristics of their deprotonated molecules. These metabolites indicated that isorhamnetin-3-O-neohesperidoside was firstly deglycosylated to isorhamnetin-3-O-glucoside and subsequently to the aglycone isorhamnetin, and the latter was demethylated to quercetin. The majority of bacteria such as Escherichia sp. 23 were capable of converting isorhamnetin-3-O-neohesperidoside to considerable amounts of aglycone isorhamnetin and further to minor amounts of quercetin, while minor amounts of isorhamnetin-3-O-glucoside were detected in minority of bacterial samples such as Enterococcus sp. 30. The metabolic pathway and metabolites of isorhamnetin-3-O-neohesperidoside by the different human intestinal bacteria were firstly investigated. Furthermore, the metabolites of isorhamnetin-3-O-neohesperidoside might influence the effects of traditional herb medicines. Thus, our study is helpful to further unravel how isorhamnetin-3-O-neohesperidoside and Puhuang work in vivo. 10.1093/chromsci/bmw176
    Could the gut microbiota reconcile the oral bioavailability conundrum of traditional herbs? Chen Feng,Wen Qi,Jiang Jun,Li Hai-Long,Tan Yin-Feng,Li Yong-Hui,Zeng Nian-Kai Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:A wealth of information is emerging about the impact of gut microbiota on human health and diseases such as cardiovascular diseases, obesity and diabetes. As we learn more, we find out the gut microbiota has the potential as new territory for drug targeting. Some novel therapeutic approaches could be developed through reshaping the commensal microbial structure using combinations of different agents. The gut microbiota also affects drug metabolism, directly and indirectly, particularly towards the orally administered drugs. Herbal products have become the basis of traditional medicines such as traditional Chinese medicine and also been being considered valuable materials in modern drug discovery. Of note, low oral bioavailability but high bioactivity is a conundrum not yet solved for some herbs. Since most of herbal products are orally administered, the herbs' constituents are inevitably exposed to the intestinal microbiota and the interplays between herbal constituents and gut microbiota are expected. Emerging explorations of herb-microbiota interactions have an opportunity to revolutionize the way we view herbal therapeutics. The present review aims to provide information regarding the health promotion and/or disease prevention by the interplay between traditional herbs with low bioavailability and gut microbiota through gut microbiota via two different types of mechanisms: (1) influencing the composition of gut microbiota by herbs and (2) metabolic reactions of herbal constituents by gut microbiota. MATERIALS AND METHODS:The major data bases (PubMed and Web of Science) were searched using "gut microbiota", "intestinal microbiota", "gut flora", "intestinal flora", "gut microflora", "intestinal microflora", "herb", "Chinese medicine", "traditional medicine", or "herbal medicine" as keywords to find out studies regarding herb-microbiota interactions. The Chinese Pharmacopoeia (2010 edition, Volume I) was also used to collect the data of commonly used medicinal herbs and their quality control approaches. RESULTS:Among the 474 monographs of herbs usually used in the Chinese Pharmacopoeia, the quality control approach of 284 monographs is recommended to use high-performance liquid chromatography approach. Notably, the major marker compounds (>60%) for quality control are polyphenols, polysaccharides and saponins, with significant oral bioavailability conundrum. Results from preclinical and clinical studies on herb-microbiota interactions showed that traditional herbs could exert heath promotion and disease prevention roles via influencing the gut microbiota structure. On the other hand, herb constituents such as ginsenoside C-K, hesperidin, baicalin, daidzin and glycyrrhizin could exert their therapeutic effects through gut microbiota-mediated bioconversion. CONCLUSIONS:Herb-microbiota interaction studies provide novel mechanistic understanding of the traditional herbs that exhibit poor oral bioavailability. "Microbiota availability" could be taken consideration into describing biological measurements in the therapeutic assessment of herbal medicine. Our review should be of value in stimulating discussions among the scientific community on this relevant theme and prompting more efforts to complement herb-microbiota interactions studies. 10.1016/j.jep.2015.12.031
    [Establishment of model and standard operation procedure for biotransformation of chemical constituents of traditional Chinese medicine by human intestinal bacteria]. Yang Xiuwei,Xu Wei Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica OBJECTIVE:To establish human intestinal bacteria biotransformation model and the standard operation procedure for studying and assessing intestinal biotransformation of chemical constituents of traditional Chinese medicine (TCM). METHOD:The chemical constituent of TCM was incubated together with human intestinal flora or isolated strain, or their secretory enzymes at anaerobic environment and 37 degrees C. The biotransformation products were extracted by solvent extraction methods, separated by column chromatographic methods, and identified by spectroscopic analysis. The biotransformation mechanisms would be deduced by comparison of structural characteristics of the biotransformation products and the parent drug and/or compound, as well as the enzyme(s)-catalysed bioreactions. RESULT:The established biotransformation model of human intestinal bacteria is facile for operation and has the capability of converting the chemical constituent of traditional Chinese medicine. The growing cells transformation method, the resting cells transformation method or enzyme(s)-catalysed transformation method can all be selected as the transformation approach. CONCLUSION:The established human intestinal bacteria biotransformation model can be used to study the intestinal biotransformation of orally administrated chemical constituents of TCM and their biotransformation mechanism.
    Biotransformation and metabolic profile of Xian-Ling-Gu-Bao capsule, a traditional Chinese medicine prescription, with rat intestinal microflora by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry analysis. Gao Meng-Xue,Tang Xi-Yang,Zhang Feng-Xiang,Yao Zhi-Hong,Yao Xin-Sheng,Dai Yi Biomedical chromatography : BMC Xian-Ling-Gu-Bao capsule (XLGB), a well-known traditional Chinese medicine prescription, has been used for the prevention and treatment of osteoporosis. The safety and efficacy of XLGB have been confirmed based on the principle of evidence-based medicine. XLGB is usually administered orally, after which its multiple components are brought into contact with intestinal microflora in the alimentary tract and biotransformed. However, investigations on the comprehensive metabolic profile of XLGB are absent. In this study, 12 representative compounds bearing different typical structures (including iridoid glycosides, prenylated flavonol glycosides, prenylated flavonoids, triterpenoid saponins, steroidal saponins, coumarins and monoterpene phenols) were selected and then investigated for their biotransformation in rat intestinal microflora. In addition, the metabolic profile of XLGB in rat intestinal microflora was investigated by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. As a result, a total of 87 biotransformation components were identified from incubated solutions of 12 representative compounds and XLGB, which underwent 16 metabolic reactions (including deglycosylation, glycosylation, dehydrogenation, hydrogenation, oxidation, epoxidation, hydroxylation, dehydration, hydration, hydrolysis, methylation, isomerization, cyclization, pyrolysis reaction, amino acid conjugation and nucleophilic addition reaction with NH ). This demonstrated that the deglycosylation reaction by cleavage of the sugar moieties is the main metabolic pathway of a variety of glycosides, including prenylated flavonol glycosides, coumarin glycosides, iridoid glycosides and saponins. In addition, compared with the biotransformation of 12 representative compounds, a different biotransformed fate was observed in the XLGB incubated samples of rat intestinal microflora. It is worth noting that the amino acid conjugation was first discovered in the metabolism of prenylated flavonol glycosides in rat intestinal microflora. 10.1002/bmc.4160
    [Analysis of metabolites of quercitrin in rat intestinal flora by using UPLC-ESI-Q-TOF-MS/MS]. Qin Xiao-Li,Sun Hui-Yuan,Yang Wu,Li Yong-Jun,Zheng Lin,Liu Ting,Huang Yong Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica To investigate the metabolism of quercitrin in rat intestinal flora and possible biological pathways, laying the foundation for the metabolic mechanism of traditional Chinese medicine glycosides ingredients. UPLC-Q-TOF-MS/MS method was established to detect the quercitrin and its metabolites with 0.1% formic acid solution(A)-0.1% formic acid acetonitrile(B) as the mobile phase for gradient elution at a flow rate of 0.3 mL•min⁻¹. Electrospray negative ion mode was applied to analyze the metabolites of quercitrin in rat intestinal flora. Metabolite ToolsTM, mass defect filter(MDF) and other technologies were used to screen, analyze the metabolites and infer the chemical formula of the metabolites. The results showed that quercitrin would have degalactoside, deoxygenation and acetylation reactions, and the aglycone quercetin resulted from degalactoside would have further reactions such as hydroxylation, deoxygenation, reduction, and ring opening to achieve deoxygenation metabolite kaempferol, C2-C3 double bonds hydrogenation and reduction product taxifolin, and degalactoside product quercetin. The research results showed that quercitrin can be metabolized by rat intestinal flora, which could increase their hydrophobicity and chemical diversity. 10.19540/j.cnki.cjcmm.20161222.018
    Study of the Biotransformation of Tongmai Formula by Human Intestinal Flora and Its Intestinal Permeability across the Caco-2 Cell Monolayer. Wu Shuai,Xu Wei,Wang Fu-Rong,Yang Xiu-Wei Molecules (Basel, Switzerland) Tongmai formula (TMF) is a well-known Chinese medicinal preparation that contains isoflavones as its major bioactive constituents. As traditional Chinese medicines (TCMs) are usually used by oral administration, their fate inside the intestinal lumen, including their biotransformation by human intestinal flora (HIF) and intestinal absorption deserves study. In this work TMF extract was incubated with human intestinal bacteria under anaerobic conditions and the changes in the twelve main constituents of TMF were then investigated. Their intestinal permeabilities, i.e., the transport capability across the intestinal brush border were investigated with a human colon carcinoma cell line (Caco-2) cell monolayer model to predict the absorption mechanism. Meanwhile, rapid HPLC-DAD methods were established for the assay. According to the biotransformation curves of the twelve constituents and the permeability coefficients, the intestinal absorption capacity of the typical compounds was elevated from the levels of 10(-7) cm/s to 10(-5) cm/s from those of the original compounds in TMF. Among them the main isoflavone glycosides puerarin (4), mirificin (6) and daidzin (7) were transformed into the same aglycone, daidzein (10). Therefore it was predicted that the aglycone compounds might be the real active ingredients in TMF. The models used can represent a novel path for the TCM studies. 10.3390/molecules201018704
    [Effect of traditional Chinese medicine in inhibiting obesity and inflammatory diseases by regulating gut microbiota]. Sang Ting-Ting,Guo Cheng-Jie,Guo Dan-Dan,Wang Xing-Ya Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica Traditional Chinese medicine(TCM) has been increasingly used in the prevention and treatment of obesity and obesity-related diseases. However, its mechanism of action is not yet clear. In recent years, with the development of high-throughput sequencing technology, scientific researches have found that the disorder of gut microbiota is associated with obesity and other diseases. Furthermore, it has been found that TCM can improve the structure of gut microbiota by increasing probiotics and reducing pathogens, which play an importent role in preventing the development and progression of obesity and other diseases. This article first explores the possible association between intestinal microbiota and obesity. Then, it reviews the traditional Chinese medicine and its role in regulating intestinal microbiota for the prevention and treatment of diseases, including obesity and inflammation, insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, inflammatory bowel disease and other diseases, in theexpectation of new strategies and research direction for treating obesity and relevant diseases, and providing important guidance for further studies in this field in the future. 10.19540/j.cnki.cjcmm.20180423.003
    [Incompatible mechanism of compatibility of Chinese medicines based on Qianjinzi and Gancao effect on intestinal flora/barrier system]. Tao Wei-Wei,Yu Jin-Gao,Chen Yan-Yan,Xiao Dong,Guo Jian-Ming,Liu Pei,Duan Jin-Ao Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica The study was based on the toxic characteristics of the compatibility between "Zaojisuiyuan" and Gancao, with intestinal tract and intestinal bacteria as subject. From the angle of intestinal barrier function, motor function, steady state of intestinal flora and metabolism genes, the toxic and side effects of the compatibility between Qianjinzi and Gancao with similar properties, bases and chemical composition and types were further explored. The results showed that the combined application of Qianjinzi and Gancao enhanced intestinal mucosa damage, and led to abnormal changes in intestinal bacteria structure and metabolic function. It improved the degradation functions of mucus and aromatic amino acids on intestinal bacteria, which may increase the risk of disease and derived from intestinal urotoxin and other toxic substances. This study considered intestinal bacteria as an important target to study the interactions of traditional Chinese medicine. The "drug-intestinal bacteria-metabolism-toxicity" was applied in the experiment. Meanwhile, it provides ideas for exploring incompatible mechanism of traditional Chinese medicines. 10.19540/j.cnki.cjcmm.20171027.021
    An Approach to Characterizing the Complicated Sequential Metabolism of Salidroside in Rats. Luo Zhiqiang,Ma Xiaoyun,Liu Yang,Lu Lina,Yang Ruirui,Yu Guohua,Sun Mohan,Xin Shaokun,Tian Simin,Chen Xinjing,Zhao Haiyu Molecules (Basel, Switzerland) Metabolic study of bioactive compounds that undergo a dynamic and sequential process of metabolism is still a great challenge. Salidroside, one of the most active ingredients of Rhodiola crenulata, can be metabolized in different sites before being absorbed into the systemic blood stream. This study proposed an approach for describing the sequential biotransformation process of salidroside based on comparative analysis. In vitro incubation, in situ closed-loop and in vivo blood sampling were used to determine the relative contribution of each site to the total metabolism of salidroside. The results showed that salidroside was stable in digestive juice, and it was metabolized primarily by the liver and the intestinal flora and to a lesser extent by the gut wall. The sequential metabolism method described in this study could be a general approach to characterizing the metabolic routes in the digestive system for natural products. 10.3390/molecules21060706
    Facilitation of Gastrointestinal (GI) Tract Microbiome-Derived Lipopolysaccharide (LPS) Entry Into Human Neurons by Amyloid Beta-42 (Aβ42) Peptide. Lukiw Walter J,Li Wenhong,Bond Taylor,Zhao Yuhai Frontiers in cellular neuroscience Human gastrointestinal (GI)-tract microbiome-derived lipopolysaccharide (LPS): (i) has been recently shown to target, accumulate within, and eventually encapsulate neuronal nuclei of the human central nervous system (CNS) in Alzheimer's disease (AD) brain; and (ii) this action appears to impede and restrict the outward flow of genetic information from neuronal nuclei. It has previously been shown that in LPS-encased neuronal nuclei in AD brain there is a specific disruption in the output and expression of two AD-relevant, neuron-specific markers encoding the cytoskeletal neurofilament light (NF-L) chain protein and the synaptic phosphoprotein synapsin-1 (SYN1) involved in the regulation of neurotransmitter release. The biophysical mechanisms involved in the facilitation of the targeting of LPS to neuronal cells and nuclei and eventual nuclear envelopment and functional disruption are not entirely clear. In this "Perspectives article" we discuss current advances, and consider future directions in this research area, and provide novel evidence in human neuronal-glial (HNG) cells in primary culture that the co-incubation of LPS with amyloid-beta 42 (Aβ42) peptide facilitates the association of LPS with neuronal cells. These findings: (i) support a novel pathogenic role for Aβ42 peptides in neurons the formation of pores across the nuclear membrane and/or a significant biophysical disruption of the neuronal nuclear envelope; and (ii) advance the concept that the Aβ42 peptide-facilitated entry of LPS into brain neurons, accession of neuronal nuclei, and down-regulation of neuron-specific components such as NF-L and SYN1 may contribute significantly to neuropathological deficits as are characteristically observed in AD-affected brain. 10.3389/fncel.2019.00545
    Effects of Qijian mixture on type 2 diabetes assessed by metabonomics, gut microbiota and network pharmacology. Gao Kuo,Yang Ran,Zhang Jian,Wang Zhiyong,Jia Caixia,Zhang Feilong,Li Shaojing,Wang Jinping,Murtaza Ghulam,Xie Hua,Zhao Huihui,Wang Wei,Chen Jianxin Pharmacological research Qijian mixture, a new traditional Chinese medicine (TCM) formula comprising of Astragalus membranaceus, Ramulus euonymi, Coptis chinensis and Pueraria lobata, was designed to ameliorate the type 2 diabetes (T2D), and its safety and efficacy were evaluated in the research by metabonomics, gut microbiota and system pharmacology. To study the hypoglycemic effect of Qijian mixture, male KKay mice (28-30 g, 8-9 week) and C57/BL6 mice (18-19 g, 8-9 week) were used. Thirty KKay diabetic mice were randomly distributed into 5 groups, abbreviated as Model group (Model), Low Qijian Mixture group (QJM(L)), High Qijian Mixture group (QJM(H)), Chinese Medicine (Gegen Qinlian Decoction) Positive group (GGQL), and Western Medicine (Metformin hydrochloride) Positive group (Metformin). C57/BL6 was considered as the healthy control group (Control). Moreover, a system pharmacology approach was utilized to assess the physiological targets involved in the action of Qijian mixture. There was no adverse drug reaction of Qijian mixture in the acute toxicity study and HE result, and, compared with Model group, Qijian mixture could modulate blood glycemic level safely and effectively. Qijian Mixture was lesser effective than metformin hydrochloride; however, both showed similar hypoglycemic trend. Based on H NMR based metabonomics study, the profoundly altered metabolites in Qijian mixture treatment group were identified. Qijian mixture-related 55 proteins and 4 signaling pathways, including galactose metabolism, valine, leucine and isoleucine degradation metabolism, aminoacyl-tRNA biosynthesis metabolism and alanine, aspartate and glutamate metabolism pathways, were explored. The PCoA analysis of gut microbiota revealed that Qijian mixture treatment profoundly enriched bacteroidetes. In addition, the system pharmacology paradigm revealed that Qijian mixture acted through TP53, AKT1 and PPARA proteins. It was concluded that Qijian mixture effectively alleviated T2D, and this effect was linked with the altered features of the metabolite profiles and the gut microbiota. 10.1016/j.phrs.2018.01.011
    Traditional Chinese medicine: balancing the gut ecosystem. Li Houkai,Zhou Mingmei,Zhao Aihua,Jia Wei Phytotherapy research : PTR Gut microflora has become a topic of interest in life sciences in the context of global systems biology, in which human biological system is viewed as 'superorganisms' involving an internal ecosystem of diverse microbiome. We conceive that multi-pathway modulations of the human gut microbial system exerted by traditional Chinese medicines (TCMs) to restore the balance of the gut ecology may account for a large portion of their effectiveness in host during treatment. Such a concept is evidenced by series of studies which have revealed an interactive relationship between gut microflora and TCM, involving the two important aspects: gut microflora-dependent drug metabolism in TCM and gut microflora-targeted modulation of physiological conditions, both of which highlight the significance of gut microflora involvement in the future TCM investigation. 10.1002/ptr.2590
    The anti-hyperglycemia effects of Rhizoma Coptidis alkaloids: A systematic review of modern pharmacological studies of the traditional herbal medicine. Ma Hang,He Kai,Zhu Jianwei,Li Xuegang,Ye Xiaoli Fitoterapia Hyperglycemia is a common endocrine system disease, which seriously affects people's health with a increasing morbidity in recent years. Rhizoma Coptidis (RC), one of the most commonly used traditional Chinese medicines, has been applied to treat diabetes in clinic for thousands of years. Since scientists demonstrated that alkaloids from RC owned the amazing anti-hyperglycemia activities 30 years ago, these compounds have been widely used for the treatment of diabetes and hyperglycemia with unconspicuous toxicities and side effects. With the help of molecular biology, immunology and other techniques, the mechanisms about anti-hyperglycemia effect of RC alkaloids have been extensively discussed. Numerous studies showed that RC alkaloids balanced the glucose homeostasis not only by widely recognizing insulin resistance pathways, but also by promoting insulin secretion, regulating intestinal hormones, ameliorating gut microbiota structures and many other ways. In this review, we combine the latest advances and systematically summarize the mechanisms of RC alkaloids in treating hyperglycemia and diabetic nephropathy to provide a deeper understanding of these natural alkaloids. In addition, the important role of gut microbiota associated with the glucose metabolism is also reviewed. 10.1016/j.fitote.2019.03.003
    A metabolic mechanism analysis of Fuzheng-Huayu formula for improving liver cirrhosis with traditional Chinese medicine syndromes. Song Ya-Nan,Chen Jian,Cai Fei-Fei,Lu Yi-Yu,Chen Qi-Long,Zhang Yong-Yu,Liu Ping,Su Shi-Bing Acta pharmacologica Sinica Fuzheng-Huayu formula (FZHY), a Chinese herbal mixture prescription, has been proven effective in treating liver fibrosis and cirrhosis in both clinical trials and animal experiments. In this study we assessed the metabolic mechanisms of traditional Chinese medicine (TCM) syndrome-based FZHY treatment in liver cirrhosis (LC). A total of 113 participants, including 50 healthy controls and 63 LC patients, were recruited. According to the diagnosis and differentiation of the TCM syndromes, the LC patients were classified into 5 TCM syndrome groups including the liver stagnation syndrome (LSS), spleen deficiency and damp overabundance syndrome (SDDOS), damp-heat accumulation syndrome (DHAS), liver-kidney Yin deficiency syndrome (LKYDS), and blood stagnation syndrome (BSS), and administered FZHY for 6 months. FZHY treatment significantly decreased serum levels of hyaluronic acid (HA), a biochemical marker for LC, as well as TCM syndrome scores (the TCM syndrome scores were decreased in all the groups with significant decreases in the LSS and LKYDS groups). Furthermore, FZHY treatment gradually shifted the metabolic profiles of LC patients from a pathologic state to a healthy state, especially in LC patients with LSS and LKYDS. Twenty-two differently altered metabolites (DAMs) were identified, including carbohydrates, amino acids, fatty acids, etc with 9 DAMs in LSS patients, 9 in LKYDS patients, and 4 in other patients. The metabolic pathways involved in the conversion of amino acids and the body's detoxification process were regulated first, followed by the pathways involved in the body's energy supply process. In conclusion, the evaluation of the effect of TCM syndrome-based FZHY treatment show that FZHY has a better effect on LKYDS and LSS than on the other TCM syndromes, and the metabolic mechanisms might be involved in the increased detoxification function in LKYDS and the improvement of energy supply in LSS, which provides important evidence for the clinical application of TCM syndrome-based treatment. 10.1038/aps.2017.101
    The Progress of Metabolomics Study in Traditional Chinese Medicine Research. Wang Pengcheng,Wang Qiuhong,Yang Bingyou,Zhao Shan,Kuang Haixue The American journal of Chinese medicine Traditional Chinese medicine (TCM) has played important roles in health protection and disease treatment for thousands of years in China and has gained the gradual acceptance of the international community. However, many intricate issues, which cannot be explained by traditional methods, still remain, thus, new ideas and technologies are needed. As an emerging system biology technology, the holistic view adopted by metabolomics is similar to that of TCM, which allows us to investigate TCM with complicated conditions and multiple factors in depth. In this paper, we tried to give a timely and comprehensive update about the methodology progression of metabolomics, as well as its applications, in different fields of TCM studies including quality control, processing, safety and efficacy evaluation. The herbs investigated by metabolomics were selected for detailed examination, including Anemarrhena asphodeloides Bunge, Atractylodes macrocephala Kidd, Pinellia ternate, etc.; furthermore, some valuable results have been obtained and summarized. In conclusion, although the study of metabolomics is at the early phase and requires further scrutiny and validation, it still provides bright prospects to dissect the synergistic action of multiple components from TCM. Overall, with the further development of analytical techniques, especially multi-analysis techniques, we expect that metabolomics will greatly promote TCM research and the establishment of international standards, which is beneficial to TCM modernization. 10.1142/S0192415X15500731
    Application of proteomics in research on traditional Chinese medicine. Suo Tongchuan,Wang Haixia,Li Zheng Expert review of proteomics INTRODUCTION:Traditional Chinese medicine (TCM) is a widely used complementary alternative medicine approach. Although many aspects of its effectiveness have been approved clinically, rigorous scientific techniques are highly required to translate the promises from TCM into powerful modern therapies. In this respect, proteomics is useful because of its ability to unveil the underlying target proteins and/or protein biomarkers. AREAS COVERED:In this review, we summarize the recent interplay between proteomics and research on TCM, ranging from exploration of the medicinal materials to the biological basis of TCM concepts, and from pathological studies to pharmacological investigations. We show that proteomic analyses provide preliminary biological evidence of the promises in TCM, and the integration of proteomics with other omics and bioinformatics offers a comprehensive methodology to address the complications of TCM. Expert commentary: Currently, only limited information can be obtained regarding TCM issues and thus more work is required to resolve the ambiguity. As such, more collaborations between proteomics and other techniques (other omics, network pharmacology, etc.) are essential for deciphering the underlying biological basis in TCM topics. 10.1080/14789450.2016.1220837
    Gut microbiota modulation with traditional Chinese medicine: A system biology-driven approach. Yue Shi-Jun,Wang Wen-Xiao,Yu Jin-Gao,Chen Yan-Yan,Shi Xu-Qin,Yan Dan,Zhou Gui-Sheng,Zhang Li,Wang Chang-Yun,Duan Jin-Ao,Tang Yu-Ping Pharmacological research With the development of system biology, traditional Chinese medicine (TCM) is drawing more and more attention nowadays. However, there are still many enigmas behind this ancient medical system because of the arcane theory and complex mechanism of actions. In recent decades, advancements in genome sequencing technologies, bioinformatics and culturomics have led to the groundbreaking characterization of the gut microbiota, a 'forgotten organ', and its role in host health and disease. Notably, gut microbiota has been emerging as a new avenue to understanding TCM. In this review, we will focus on the structure, composition, functionality and metabolites of gut microbiota affected by TCM so as to conversely understand its theory and mechanisms. We will also discuss the potential areas of gut microbiota for exploring Chinese material medica waste, Chinese marine material medica, add-on therapy and personalized precise medication of TCM. The review will conclude with future perspectives and challenges of gut microbiota in TCM intervention. 10.1016/j.phrs.2019.104453
    [Application of network biology on study of traditional Chinese medicine]. Tian Sai-Sai,Yang Jian,Zhao Jing,Zhang Wei-Dong Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica With the completion of the human genome project, people have gradually recognized that the functions of the biological system are fulfilled through network-type interaction between genes, proteins and small molecules, while complex diseases are caused by the imbalance of biological processes due to a number of gene expression disorders. These have contributed to the rise of the concept of the "multi-target" drug discovery. Treatment and diagnosis of traditional Chinese medicine are based on holism and syndrome differentiation. At the molecular level, traditional Chinese medicine is characterized by multi-component and multi-target prescriptions, which is expected to provide a reference for the development of multi-target drugs. This paper reviews the application of network biology in traditional Chinese medicine in six aspects, in expectation to provide a reference to the modernized study of traditional Chinese medicine. 10.19540/j.cnki.cjcmm.20171027.018
    Methods of analysis of gut microorganism--actual state of knowledge. Ignyś Iwona,Szachta Patrycja,Gałęcka Mirosława,Schmidt Marcin,Pazgrat-Patan Michalina Annals of agricultural and environmental medicine : AAEM INTRODUCTION:Microbiota plays an integral part in maintaining organism homeostasis, through eliminat pathogens, anti-cancer activity, synthesis of digestive enzymes and vitamins, maintaining the continuity of the intestinal epithelium and stimulation of the gastrointestinal immune system, and encourage a quicker and more efficient immune response. Changes in the microbiota composition is often observed in patients with allergy, atopy, irritable bowel syndrome and other diseases, which is the reason for a growing interest in methods of identification of the gut microbial complex. OBJECTIVE:The aim of the study was to compare the state of current knowledge about two methods used in the study of intestinal microorganisms complex: the traditional culture method and genetic analysis. DESCRIPTION OF THE STATE OF KNOWLEDGE: Both techniques have advantages and disadvantages. The biggest limitation of the culture method is its inability to detect a significant number of the intestinal microbes. Using the microbiological technique we can only detect identifiable bacteria that can be grown on available substrates. For an accurate quantitative and qualitative investigation of the total microbiota, the more expensive genetic method is required. Due to genetic analysis it is possible to identify the vast number of new microorganisms and identify the dominant bacterial groups in different parts of the gastrointestinal tract. SUMMARY:Each of the presented techniques plays specific role in medicine and science. The combination of both methods may become a critical element for understanding the ecosystem of intestinal bacteria. 10.5604/12321966.1129936
    Intake of total saponins and polysaccharides from Polygonatum kingianum affects the gut microbiota in diabetic rats. Yan Hongli,Lu Jianmei,Wang Yanfang,Gu Wen,Yang Xingxin,Yu Jie Phytomedicine : international journal of phytotherapy and phytopharmacology BACKGROUND:The gut microbiota has been reported to play a critical role in metabolic diseases, including in diabetes. Polygonatum kingianum has been used in the treatment of diabetes and related diseases in China for centuries. Total saponins (TSPK) and total polysaccharides (PSPK) were reported to be major types of active constituents of P. kingianum. This research aims at investigation of their therapeutical mechanisms on diabetes based on the regulation of gut microbiota. STUDY DESIGN:Type 2 diabetes (T2D) rats were induced by high-fat diet (HFD) and streptozotocin-injection from male Sprague-Dawley (SD) rats. The blood biochemical indicators were measured. Intestinal microbial diversities and the overall structural changes in gut microbiota and the contents of the short chain fatty acids (SCFAs) were discussed. METHODS:T2D rats were treated with TSPK (0.025 and 0.1g/kg) and PSPK (0.1g/kg) for 56 days. Major biochemical indexes, such as fasting blood glucose (FBG), fasting insulin (FINS) and lipopolysaccharide (LPS), were measured. Intestinal microbial diversities and the overall structural changes in gut microbiota were discussed based on the sequencing results on V4 region of 16S rDNA. Moreover, the contents of the SCFAs in faeces, which were fermentation products produced from gut microbiota were determined by gas chromatography (GC). RESULTS:Oral administration of TSPK and PSPK prevented the increase of FBG. TSPK (0.025g/kg) enhancing the content of FINS at the end of research. Furthermore, TSPK and PSPK improved the intestinal microecology by decreasing the abundances of Bacteroidetes and Proteobacteria, and increasing that of Firmicutes. However, TSPK.L, PSPK and TSPK.H displayed discrepant regulation roles on Firmicutes. TSPK.L and PSPK significantly increased the abundance of Ruminococcaceae family and Ruminococcus genus in Firmicutes phylum, however, TSPK.H increased the abundances of Veillonellaceae family and Anaerovibrio genus. 57 Key variables, altered after treated by TSPK and PSPK, correlated to the alternations of FBG, FINS, LPS and body weight were identified. In addition, TSPK.L, PSPK and TSPK.H showed different adjustment on the contents of SCFAs. CONCLUSION:These results suggested that, compared to the normal rats, the structure of gut microbiota was significantly changed in diabetic rats. Oral administration with TSPK and PSPK could prevent T2D by its regulation role on the gut microbiota. 10.1016/j.phymed.2017.01.007
    Volatile Oil of Inhibits Nonalcoholic Fatty Liver Disease via the Gut-Liver Axis. Lu Shanhong,Zhang Ting,Gu Wen,Yang Xingxin,Lu Jianmei,Zhao Ronghua,Yu Jie BioMed research international Background:The dried mature fruit of has been historically used in China as food and in the auxiliary treatment of digestive system disorders. Numerous studies have shown that gastrointestinal function is closely related to the development of nonalcoholic fatty liver disease via the "gut-liver" axis. Objective:The present study aimed to explore whether the mechanism underlying the regulation of lipid accumulation in nonalcoholic fatty liver disease (NAFLD) may affect related disorders using the active ingredients in . Design:Male Sprague-Dawley rats on a high-fat diet (HFD) to induce NAFLD were administered water extract of (WEAV), volatile oil of (VOAV), or bornyl acetate. After treatment, serum and liver total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. The regulatory role of in the microecology of the intestines was assessed using the V4 region of the 16S rDNA sequencing. The expression of the intestinal tight junction proteins occludin and ZO-1 was also measured. The influence of on TLR4-mediated chronic low-grade inflammation was evaluated based on the concentrations of key proteins of the TLR4/NF-кB signaling pathway. effectively inhibited endogenous lipid synthesis, reduced TG, TC, and FFA accumulation, regulated the expression of LDL-C, and decreased lipid accumulation in liver tissues. VOAV effectively regulated the intestinal microflora, improved chronic low-grade inflammation by promoting ZO-1 and occludin protein expressions, and inhibited the TLR4/NF-кB signaling pathway. Conclusion:The present study provides scientific basis for the potential application of in NAFLD prevention and treatment. Additional chemical constituents other than bornyl acetate also contributed to the preventive effects of on NAFLD. 10.1155/2018/3589874
    Changes of Intestinal Microecology in Patients with Primary Sjogren's Syndrome after Therapy of Yangyin Yiqi Huoxue Recipe (). Wu Guo-Lin,Lu Hai-Feng,Chen Yi-Lian,Wang Qing,Cao Heng,Li Tian-Yi Chinese journal of integrative medicine OBJECTIVE:To explore the change of intestinal microecology in patients with primary Sjogren's syndrome (pSS) and correlation with disease activity, and also discuss the therapy effect of Yangyin Yiqi Huoxue Recipe (, YYHD). METHODS:Sixteen pSS patients were enrolled in the present study, who received 3-month treatment of YYHR, 200 mL orally twice daily. Their pre-and post-test ESSDAI scores, erythrocyte sedimentation rate (ESR) and serum immunoglobulin G (IgG) levels were measured respectively. The 16SrDNA metagenomic sequencing was used to detect and analyze the abundance and diversity of intestinal bacteria flora and the proportion of bacteria at the levels of phylum, family, and genus, in comparision with those of 6 healthy subjects in the control group. RESULTS:The abundance and diversity of intestinal bacteria flora in pSS patients were lower than those of healthy subjects (P<0.05). After the treatment with YYHD, patients' ESSDAI score and levels of IgG and ESR have decreased significantly (P<0.05). At the phylum level, the proportions of Actinobacteria, Firmicutes, Fusobacteria and Proteobacteria have reduced sharply, while the proportions of Bacteroidetes, Teneriquetes and Candidate-division-TM7 have increased significantly by treatment (all P<0.05). At the classification level, such treatment has caused a significant decrease in the proportions of Bacteroidaceae, Ruminococcaceae, Veillonellaceae, and Enterobacteriacea (all P<0.05), but a significant increase in the proportion of Lachnospiraceae (P<0.05). At the genus level, the treatment has significantly decreased the proportions of Bifidobacterium, Bacteroides, Escherichia-Shigella, Faecalibacterium and Prevotella (all P<0.05), but significantly increased the proportion of Clostridia (P<0.05), close to the levels of healthy subjects (P>0.05). CONCLUSIONS:There exists an imbalance of intestinal microecology in pSS patients, which can be improved through the treatment with YYHD. Besides, such treatment can also improve the disease activity and adjust the diversity of intestinal bacteria flora, the composition and the abundance of intestinal flora. 10.1007/s11655-019-2939-4
    [Chinese medicinal compound and modulation of intestinal microecology]. Li Guo,Xiao Xiao-He,Jin Cheng Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine Focusing on the relationship of intestinal microecology with the physiologic function and pathologic manifestation, literature in recent years on mechanisms of Chinese wedicinal compounds for regulating disease associated intestinal microecology are reviewed in this paper, so as to provide a new approach and idea for scientific research and clinical application of Chinese wedicinal compounds.
    [Research status on regulation of Chinese herbal compound on intestinal microecology]. Wu Guo-lin,Yu Guo-you,Lu Wen-wen Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica The ralationship between traditional Chinese medicine (TCM) and intestinal microecology is increasingly being given more and more attention. Combined with the devolopment of intestinal microecology disciplines, effects of TCM on regulation of intestinal microecology have been gradually explained. Both clinical studies and animal experiments have confirmed that TCM can maintain the balance of intestinal microecology and regulate the intestinal flora. The author arrangemented the documents related to Chinese herbal compound adjusting intestinal flora in the recent ten years, summarized that the Chinese herbal compound which can strength spleen and replenish Qi, relax bowels and regulate Qi, dissipate dampness and check diarrhea, clear away heat and toxic materials, promote digestion and relieve stasis had certain regulation effects on intestinal microecology, providing basis for revealing the TCM essence of intestinal microecology.
    Role of stem cell growth factor/c-Kit in the pathogenesis of irritable bowel syndrome. Chai Yuna,Huang Yusheng,Tang Hongmei,Tu Xing,He Jianbo,Wang Ting,Zhang Qingye,Xiong Fen,Li Detang,Qiu Zhenwen Experimental and therapeutic medicine Irritable bowel syndrome (IBS) is a functional bowel disease with a complicated etiopathogenesis, often characterized by gastrointestinal motility disorder and high visceral sensitivity. IBS is a comprehensive multi-systemic disorder, with the interaction of multiple factors, such as mental stress, intestinal function and flora, heredity, resulting in the disease. The existence of a common mechanism underlying the aforementioned factors is currently unknown. The lack of therapies that comprehensively address the disease symptoms, including abdominal pain and diarrhea, is a limitation of current IBS management. The current review has explored the role of the SCF/c-Kit receptor/ligand system in IBS. The SCF/c-Kit system constitutes a classical ligand/receptor tyrosine kinase signaling system that mediates inflammation and smooth muscle contraction. Additionally, it provides trophic support to neural crest-derived cell types, including the enteric nervous system and mast cells. The regulation of SCF/c-Kit on the interstitial cells of Cajal (ICC) suggest that it may play a key role in the aberrant intestinal dynamics and high visceral sensitivity observed in IBS. The role of the SCF/c-Kit system in intestinal motility, inflammation and nerve growth has been reported. From the available biomedical evidence on the pathogenesis of IBS, it has been concluded that the SCF-c-Kit system is a potential therapeutic target for rational drug design in the treatment of IBS. 10.3892/etm.2017.4133
    Helicobacter pylori infection alters gastric and tongue coating microbial communities. Zhao Yubin,Gao Xuefeng,Guo Jiaxuan,Yu Dongbao,Xiao Ying,Wang Huijie,Li Yuchan Helicobacter OBJECTIVE:Infection with Helicobacter pylori (H pylori), especially cytotoxin-associated gene A-positive (CagA+) strains, has been associated with various gastrointestinal and extragastric diseases. The aim of this study was to characterize H pylori-induced alterations in the gastric and tongue coating microbiota and evaluate their potential impacts on human health. DESIGN:The gastric mucosa and tongue coating specimens were collected from 80 patients with chronic gastritis, and microbiota profiles were generated by 16S rRNA gene sequencing. Samples were grouped as H pylori negative (n = 32), CagA-negative H pylori infection (n = 13), and CagA-positive H pylori infection (n=35). The comparison of bacterial relative abundance was made using a generalized linear model. Functional profiling of microbial communities was predicted with PICRUSt and BugBase. Microbial correlation networks were produced by utilizing SparCC method. RESULTS:Significant alterations of the gastric microbiota were found in the H pylori+/CagA+ samples, represented by a decrease in bacterial diversity, a reduced abundance of Roseburia, and increased abundances of Helicobacter and Haemophilus genera. At the community level, functions involved in biofilm forming, mobile element content, and facultative anaerobiosis were significantly decreased in gastric microbiome of the H pylori+ subjects. The presence of CagA gene was linked to an increased proportion of Gram-negative bacteria in the stomach, thereby contributing to an upregulation of lipopolysaccharide (LPS) biosynthesis. The number of bacterial interactions was greatly reduced in networks of both tongue coating and gastric microbiota of the H pylori+/CagA+ subject, and the cooperative bacterial interactions dominated the tongue coating microbiome. CONCLUSIONS:Infection with H pylori strains possessing CagA may increase the risk of various diseases, by upregulating LPS biosynthesis in the stomach and weakening the defense of oral microbiota against microorganisms with pathogenic potential. 10.1111/hel.12567
    The critical role of calcineurin/NFAT (C/N) pathways and effective antitumor prospect for colorectal cancers. Gang Wang,Yu-Zhu Wang,Yang Yu,Feng Shi,Xing-Li Fu,Heng Zhang Journal of cellular biochemistry Transcription factors (TFs) like a nuclear factor of activated T-cells (NFAT) and its controller calcineurin are highly expressed in primary intestinal epithelial cells (IECs) due to delamination, damage by tumor-associated flora and selective activation in the intestinal tract tumor are crucial in the progression and growth of colorectal cancer (CRC). This study sought to summarize the current findings concerning the dysregulated calcineurin/NFAT (C/N) signaling involved in CRC initiation and progression. These signalings include proliferation, T-cell functions, and glycolysis with high lactate production that remodels the acidosis, which genes in tumor cells provide an evolutionary advantage, or even increased their attack phenotype. Moreover, the relationship between C/N and gut microbiome in CRC, especially role of NFAT and toll-like receptor signaling in regulating intestinal microbiota are also discussed. Furthermore, this review will discuss the proteins and genes relating to C/N induced acidosis in CRC, which includes ASIC2 regulated C/N1 and TFs associated with the glycolytic by-product that affect T-cell functions and CRC cell growth. It is revealed that calcineurin or NFAT targeting to antitumor, selective calcineurin inhibition or targets in NFAT signaling may be useful for clinical treatment of CRC. This can further aid in the identification of specific targets via cancer patient-personalized approach. Future studies should be focused on targeting to C/N or TLR signaling by the combination of therapeutic agents to regulate T-cell functions and gut microbiome for activating potent anticancer property with the prospect of potentiating the antitumor therapy for CRC. 10.1002/jcb.29243
    Aspirin inhibited the metastasis of colon cancer cells by inhibiting the expression of toll-like receptor 4. Ying Jun,Zhou Hai-Yang,Liu Peng,You Qing,Kuang Fei,Shen Yi-Nan,Hu Zhi-Qian Cell & bioscience Background:The metastasis of colorectal cancer frequently tends to liver, which is one of the three leading causes of cancer-related deaths worldwide. Growing evidence showed that aspirin could effectively inhibit liver metastasis of colorectal cancer. However, the potential mechanism has not been fully understood. Methods:Mouse splenic vein metastasis assay was used to examine the metastatic ability of colon cancer cells in vivo. And wound healing and transwell assay were applied to detect the metastasis potential of C26 and HCT116 colon cancer cell lines in vitro. RT-PCR and western blotting were used to explore Toll-like receptor 4 (TLR4) expression in colon cancer cell lines. The functions of TLR4 in the migration of the colon cancer cell line were analyzed by infecting cells with lentivirus containing TLR4 siRNA. Results:We demonstrated that lipopolysaccharides (LPS) could enhance the metastasis potential of C26 and HCT116 colon cancer cell lines. However, aspirin effectively decreased the metastasis capacity of colon cancer cells in vitro and in vivo. We found that the enhancement of LPS on the migration of colon cancer cells by inducing epithelial-mesenchymal transition (EMT) phenotype demonstrated a TLR4-dependent manner. Aspirin treatment lead to the downregulation of TLR4 on C26 cells which resulted in the decrease of C26 cells migration and EMT phenotype that induced by LPS. Additionally, the inhibitory effect from aspirin on the expression of TLR4 on C26 cells leads to the downregulation of NF-κB. Conclusion:The results of our study indicate that LPS origin from intestinal flora may promote the metastasis of colon cancer to liver and aspirin may inhibit the metastasis of colon cancer by inhibiting the expression of TLR4. 10.1186/s13578-017-0198-7
    Recent advances in polysaccharides from Ophiopogon japonicus and Liriope spicata var. prolifera. Fang Jiacheng,Wang Xiaoxiao,Lu Mengxin,He Xirui,Yang Xinhua International journal of biological macromolecules O. japonicus and L. spicata var. prolifera are distinguished as sources of highly promising yin-tonifying medicinals, namely Ophiopogonis Radix and Liriopes Radix. Liriopes Radix is generally medicinally used as a substitute for Ophiopogonis Radix in various prescriptions due to their extremely similar nature. Ophiopogonis Radix and Liriopes Radix are both very rich in bioactive polysaccharides, especially β‑fructans. Over the past twelve years, except for work on physical entrapment and chemical modification of obtained β‑fructans, the vast majority of studies are carried out to investigate the bioactivities of O. japonicus polysaccharides (OJP) and L. spicata var. prolifera polysaccharides (LSP), mainly including anti-diabetes, immunomodulation, anti-inflammation, antioxidation, anti-obesity, cardiovascular protection, etc. In addition, OJP and LSP are considered to have the potential to regulate intestinal flora. The main purpose of this review is to provide systematically reorganized information on structural characteristics and bioactivities of OJP and LSP to support their further therapeutic potentials and sanitarian functions. 10.1016/j.ijbiomac.2018.04.022
    Identification of in vivo and in vitro metabolites of triptolide by liquid chromatography-tandem mass spectrometry. Peng Zhi-hong,Wang Jun-jun,Du Peng,Chen Yong Journal of pharmaceutical and biomedical analysis Triptolide, a major active constituent of Tripterygium wilfordii Hook F, has multiple pharmacological activities. In this work, a rapid, sensitive and specific liquid chromatography coupled to an ion trap mass spectrometer (MS) with electrospray ionization (ESI) interface has been developed for identification of triptolide and some of its metabolites in rat urine after oral administration of a single dose (0.6 mg/kg) of triptolide to healthy rats, as well as some metabolites in vitro after incubation with rat liver microsome (RLM) and rat intestinal flora, respectively. All samples were separated on a reversed-phase C18 column using a mobile phase of acetonitrile/water (70:30, v/v) and detected by an on-line MS(n) detector. Identification and structural elucidation of the selected metabolites were performed by comparing their full scan MS(n) spectra with those of the parent drug. In this paper we identified ten metabolites in rat urine, four metabolites in RLM incubation solution and one metabolite in rat intestinal flora incubation solution, after drug administration. The metabolic reactions of triptolide that we observed in vivo were hydrolysis reaction, hydroxylation reaction, and the conjugate reaction with sulfate, glucuronide and GSH, respectively. The in vitro metabolic reactions of triptolide observed were hydrolysis and hydroxylation reactions. 10.1016/j.jpba.2012.06.026
    Relative contribution of small and large intestine to deglycosylation and absorption of flavonoids from Chrysanthemun morifolium extract. Lu Xin-Yan,Sun Dong-Li,Chen Zhong-Jian,Chen Ting,Li Li-Ping,Xu Zheng-Hao,Jiang Hui-Di,Zeng Su Journal of agricultural and food chemistry The flower of Chrysanthemum morifolium Ramat (CM) is an established part of traditional Chinese medicine (TCM). Luteolin and apigenin flavonoids are the effective components of the CM extract (CME); however, they exist in the orally consumed CME as glycosides. The present study was carried out to determine the relative contribution of the small and large intestine to the deglycosylation and absorption of flavonoids from CME using a rat model system. The distribution of luteolin and apigenin in rat gastrointestinal (GI) luminal contents, tissues, and plasmas was assessed after the oral administration of CME. The hydrolysis and absorption of CME flavonoids in different rat GI segments were further evaluated by using in situ ligated models and cell-free extracts prepared from rat GI segments. The results demonstrated that after the oral administration of CME, the magnitude of deglycosylation in rats was surprisingly high (about 30%) in the stomach and upper intestine within the first 5 min after ingestion, and early absorption in the plasma was detected. The results from site-limited administration revealed that the stomach was the initial hydrolysis site, while the duodenum was the first effective absorption site for CME flavonoids. Diminishing microbial flora in the jejunum had no significant effect on the hydrolysis of the flavonoids from CME, but the cell-free extracts prepared from rat GI segments demonstrated a strong ability to hydrolyze. Taken together, our findings suggest that enteric disposition contributes to the pharmacokinetics of luteolin and apigenin after oral administration of CME. Moreover, the upper digestive tract plays a key role in the hydrolysis and absorption of flavonoids in CME. 10.1021/jf102992r
    MDG-1, an Ophiopogon polysaccharide, regulate gut microbiota in high-fat diet-induced obese C57BL/6 mice. Shi Lin-lin,Li Yuan,Wang Yuan,Feng Yi International journal of biological macromolecules Most plant polysaccharides cannot be digested and utilized by host enzymes, and must be subjected to microbial fermentation before being assimilated by the host. MDG-1, a water-soluble β-d-fructan extracted from the roots of Ophiopogon japonicus, has potent anti-obesity and hypoglycemic effects. Interestingly, we found that MDG-1 is hardly absorbed into the blood. We presumed that MDG-1 might exhibit its potent efficacy via regulating the gut microbiota of the host. However, the overall microbiota structure variation of obese mice treated with MDG-1 and the direct metabolic consequences of MDG-1 on specific microbiota phyla remain poorly understood. Here, obese male C57BL/6 mice induced by a high-fat diet were given either vehicle or MDG-1 at a dose of 300mg/kg for 12 weeks and the overall fecal gut microbiota structure change was analyzed via pyrosequencing. On this basis, we further separated and identified the dominant bacteria of the feces from the MDG-1 treated mice. These bacteria were then cultured with MDG-1 in vitro and their metabolic profiles were analyzed via a metabonomic approach. The results showed that MDG-1 could decrease the ratio of Firmicutes/Bacteroidetes, adjust the abnormal gut microbiota to the normal state and alter their metabolic profiles. In addition, we identified that the indigestible MDG-1 could be degraded and utilized by gut microbiota that could, in turn, be assimilated and used by the host, where it exerted weight loss effects, energy metabolism promotion and boosted the immune system effectiveness. 10.1016/j.ijbiomac.2015.08.057
    [Changes of intestinal flora in senile mouse models and the antagonistic activity of the root of Astragalus membraceus (Fisch) Bge]. Yan M,Song H,Xie N,Zhang L Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica Inhaled by mice, ozone induced stronger free radical reaction in the organism and led to a series of changes similar to senility. In this way the senility mouse models were established to observe the changes of intestinal flora in senile mice. The senile mice were given the root of Astrogolus membraceus decoction orally. The results showed that the imbalance of intestinal flora in these mice was recovered.
    Ginsenoside Rb1 as an Anti-Diabetic Agent and Its Underlying Mechanism Analysis. Zhou Ping,Xie Weijie,He Shuaibing,Sun Yifan,Meng Xiangbao,Sun Guibo,Sun Xiaobo Cells and , two well-known medical plants with economic value, have a long history of use for managing various diseases in Asian countries. Accumulating clinical and experimental evidence suggests that notoginsenosides and ginsenosides, which are the major bioactive components of the plants, have a variety of beneficial effects on several types of disease, including metabolic, vascular, and central nervous system disease. Considerable attention has been focused on ginsenoside Rb1 derived from their common ownership as an anti-diabetic agent that can attenuate insulin resistance and various complications. Particularly, in vitro and in vivo models have suggested that ginsenoside Rb1 exerts various pharmacological effects on metabolic disorders, including attenuation of glycemia, hypertension, and hyperlipidemia, which depend on the modulation of oxidative stress, inflammatory response, autophagy, and anti-apoptosis effects. Regulation of these pathophysiological mechanisms can improve blood glucose and insulin resistance and protect against macrovascular/microvascular related complications. This review summarizes the pharmacological effects and mechanisms of action of ginsenoside Rb1 in the management of diabetes or diabetic complications. Moreover, a multi-target effect and mechanism analysis of its antidiabetic actions were performed to provide a theoretical basis for further pharmacological studies and new drug development for clinical treatment of type 2 diabetes. In conclusion, ginsenoside Rb1 exerts significant anti-obesity, anti-hyperglycemic, and anti-diabetic effects by regulating the effects of glycolipid metabolism and improving insulin and leptin sensitivities. All of these findings suggest ginsenoside Rb1 exerts protective effects on diabetes and diabetic complications by the regulation of mitochondrial energy metabolism, improving insulin resistance and alleviating the occurrence complications, which should be further explored. Hence, ginsenoside Rb1 may be developed as a potential anti-obesity, anti-hyperglycemic, and anti-diabetic agent with multi-target effects. 10.3390/cells8030204
    Integrative analysis of metabolome and gut microbiota in diet-induced hyperlipidemic rats treated with berberine compounds. Li Meng,Shu Xiangbing,Xu Hanchen,Zhang Chunlei,Yang Lili,Zhang Li,Ji Guang Journal of translational medicine BACKGROUND:Hyperlipidemia is a major component of metabolic syndrome, and often predicts cardiovascular diseases. We developed a new therapeutic agent berberine compounds (BC), consisting of berberine, oryzanol and vitamin B6, and determined their anti-hyperlipidemia activity and underlying mechanisms. METHODS:Male Wistar rats were fed a high fat diet (HFD) to induce hyperlipidemia, and then given BC orally for 4 weeks. Body weight and food intake were recorded weekly, and lipid profiles in serum were determined biochemically. Metabolites in serum, urine, liver and feces were analyzed by GC-MS, and the structure of microbiota was determined by 16S rDNA sequencing. RESULTS:Lipid lowering was observed in the hyperlipidemic rats upon BC treatment without apparent adverse side effects. Metabolomics analysis indicated that the BC treatment resulted in increased pyruvic acid, serotonin, and ketogenic and glycogenic amino acid levels in the serum, increased pyridoxine and 4-pyridoxic acid in the urine, decreased hypotaurine and methionine in the liver, and increased putrescine and decreased deoxycholate and lithocholate in feces. The BC treatment also resulted in an enrichment of beneficial bacteria (e.g. Bacteroides, Blautia) and a decrease in Escherichia. CONCLUSIONS:The lipid lowering effect of BC treatment in hyperlipidemic rats is associated with a global change in the metabolism of lipids, carbohydrates and amino acids, as well as the structure of microbiota. 10.1186/s12967-016-0987-5
    -positive colorectal cancer. Yang Zhenhua,Ji Guang Oncology letters Colorectal cancer (CRC) is an important threat to human health and the fourth leading cause of mortality worldwide. Accumulating evidence indicates that the composition of the intestinal flora is associated with the occurrence of CRC. (), one of the highly enriched bacteria in CRC tissues, invades the mucosa with adhesion factors and virulence proteins, interacts with the host immune system and promotes the occurrence and development of CRC and chemoresistance. infection is prevalent in human colorectal carcinoma, although the infection rate varies in different regions. may be used as a prognostic indicator of CRC. It is important to understand the multi-pathway carcinogenic mechanisms associated with CRC in order to develop novel antibacterial drugs against . The current review summarizes the role of and relevant research concerning CRC published in recent years, focusing on infection in CRC, pathogenesis of -positive CRC treatment, screening and prevention strategies against -positive CRC. 10.3892/ol.2019.10433
    Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota. Xu Jun,Chen Hu-Biao,Li Song-Lin Medicinal research reviews Herbal medicines (HMs) are much appreciated for their significant contribution to human survival and reproduction by remedial and prophylactic management of diseases. Defining the scientific basis of HMs will substantiate their value and promote their modernization. Ever-increasing evidence suggests that gut microbiota plays a crucial role in HM therapy by complicated interplay with HM components. This interplay includes such activities as: gut microbiota biotransforming HM chemicals into metabolites that harbor different bioavailability and bioactivity/toxicity from their precursors; HM chemicals improving the composition of gut microbiota, consequently ameliorating its dysfunction as well as associated pathological conditions; and gut microbiota mediating the interactions (synergistic and antagonistic) between the multiple chemicals in HMs. More advanced experimental designs are recommended for future study, such as overall chemical characterization of gut microbiota-metabolized HMs, direct microbial analysis of HM-targeted gut microbiota, and precise gut microbiota research model development. The outcomes of such research can further elucidate the interactions between HMs and gut microbiota, thereby opening a new window for defining the scientific basis of HMs and for guiding HM-based drug discovery. 10.1002/med.21431
    Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2 demethylation. Chen Lili,Jiang Bowen,Zhong Chunge,Guo Jun,Zhang Lihao,Mu Teng,Zhang Qiuhua,Bi Xiuli Carcinogenesis Freeze-dried black raspberry (BRB) powder is considered as a potential cancer chemopreventive agent. In this study, we fed azoxymethane (AOM)/dextran sodium sulfate (DSS)-treated C57BL/6J mice with a diet containing BRB anthocyanins for 12 weeks, and this led to a reduction in colon carcinogenesis. These animals had consistently lower tumor multiplicity compared with AOM/DSS-treated mice not receiving BRB anthocyanins. In AOM/DSS-treated mice, the number of pathogenic bacteria, including Desulfovibrio sp. and Enterococcus spp., was increased significantly, whereas probiotics such as Eubacterium rectale, Faecalibacterium prausnitzii and Lactobacillus were dramatically decreased, but BRB anthocyanins supplement could reverse this imbalance in gut microbiota. BRB anthocyanins also caused the demethylation of the SFRP2 gene promoter, resulting in increased expression of SFRP2, both at the mRNA and protein levels. Furthermore, the expression levels of DNMT31 and DNMT3B, as well as of p-STAT3 were downregulated by BRB anthocyanins in these animals. Taken together, these results suggested that BRB anthocyanins could modulate the composition of gut commensal microbiota, and changes in inflammation and the methylation status of the SFRP2 gene may play a central role in the chemoprevention of CRC. 10.1093/carcin/bgy009
    Intestinal dysbacteriosis activates tumor-associated macrophages to promote epithelial-mesenchymal transition of colorectal cancer. Wan Guangsheng,Xie Manli,Yu Hongjie,Chen Hongyu Innate immunity In this study we investigated the association between intestinal dysbacteriosis with colorectal cancer progress and the underlying molecular mechanisms. Tumor progression was evaluated using xenograft mice model. The epithelial-mesenchymal transition (EMT) markers were quantified by both real-time PCR and immunoblotting. The serum content of IL-6 and TNF-α were measured with ELISA kits. Cell proliferation was determined by the Cell Counting Kit-8. Intestinal dysbacteriosis was successfully simulated by the administration of a large dose of antibiotics and was demonstrated to promote xenograft tumor growth and induce EMT. Accordingly, the serum concentrations of cytokines IL-6 and TNF-α were significantly increased. Furthermore, the production and secretion of IL-6 and TNF-α were remarkably elevated in macrophages isolated from intestinal dysbiotic mice in comparison with the normal counterparts, and conditioned medium from these was shown to significantly stimulate EMT process in HT29 cells in vitro. Macrophage depletion completely abrogated the pro-tumor effect of intestinal dysbacteriosis. Our results suggest that intestinal dysbacteriosis stimulates macrophage activation and subsequently induces EMT process via secreted pro-inflammatory cytokines IL-6 and TNF-α. 10.1177/1753425918801496
    Inhibitory effects of Kampo medicine on human UGT2B7 activity. Nakagawa Nao,Katoh Miki,Yoshioka Yuko,Nakajima Miki,Yokoi Tsuyoshi Drug metabolism and pharmacokinetics Kampo medicine is traditional Japanese medicine modified from the Chinese original. Kampo medicine is a mixture of several medicinal herbs and includes many ingredients such as glycosides. Glycosides are hydrolyzed to aglycons by intestinal bacterial flora and absorbed into the body. Aglycons such as baicalein and glycyrrhetinic acid can be conjugated by UDP-glucuronosyltransferase (UGT) in human liver or small intestine. UGT2B7 is one of the major isoforms responsible for drug conjugation including morphine 3- and 3'- azido-3'-deoxythymidine (AZT) glucuronidation. The present study investigates the effects of 51 Kampo medicines, 14 medicinal herbs and 11 ingredients on UGT2B7 activity in human liver microsomes. Morphine 3-glucuronidation was inhibited by more than 50% by 9 of 51 Kampo medicines such as Ryo-kei-jutsu-kan-to. AZT glucuronidation was inhibited by more than 50% by 24 of 51 Kampo medicines such as Jumi-haidoku-to. Medicinal herbs such as Daio (Rhei Rhizoma), Kanzo (Glycyrrhizae Radix) and Keihi (Cinnamomi Cortex) exhibited more than 80% inhibition on both glucuronidations. The major ingredients of these medicinal herbs inhibited UGT2B7 activity with low K(i). Kampo medicines were found to inhibit the UGT2B7 activity and may cause drug interactions via the inhibition of UGT. 10.2133/dmpk.24.490
    Metaproteomic strategies and applications for gut microbial research. Xiao Mingming,Yang Junjun,Feng Yuxin,Zhu Yan,Chai Xin,Wang Yuefei Applied microbiology and biotechnology The human intestine hosts various complex microbial communities that are closely associated with multiple health and disease processes. Determining the composition and function of these microbial communities is critical to unveil disease mechanisms and promote human health. Recently, meta-omic strategies have been developed that use high-throughput techniques to provide a wealth of information, thus accelerating the study of gut microbes. Metaproteomics is a newly emerged analytical approach that aims to identify proteins on a large scale in complex environmental microbial communities (e.g., the gut microbiota). This review introduces the recent analytical strategies and applications of metaproteomics, with a focus on advances in gut microbiota research, including a discussion of the limitations and challenges of these approaches. 10.1007/s00253-017-8215-7
    Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota. Han Ruiting,Ma Junli,Li Houkai Frontiers of medicine Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical "Two-hit" theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a "metabolic organ" that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD. 10.1007/s11684-018-0645-9
    Distinctly altered gut microbiota in the progression of liver disease. Xie Guoxiang,Wang Xiaoning,Liu Ping,Wei Runmin,Chen Wenlian,Rajani Cynthia,Hernandez Brenda Y,Alegado Rosanna,Dong Bing,Li Defa,Jia Wei Oncotarget Recent studies underscore important roles of intestinal microbiota and the bacterial lipopolysaccharides (LPS) production in the pathogenesis of liver disease. However, how gut microbiota alters in response to the development of steatosis and subsequent progression to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remains unclear. We aimed to study the gut microbial changes over liver disease progression using a streptozotocin-high fat diet (STZ-HFD) induced NASH-HCC C57BL/6J mouse model that is highly relevant to human liver disease. The fecal microbiota at various liver pathological stages was analyzed by 16S rDNA gene pyrosequencing. Both UniFrac analysis and partial least squares-discriminant analysis showed significant structural alterations in gut microbiota during the development of liver disease. Co-abundance network analysis highlighted relationships between genera. Spearman correlation analysis revealed that the bacterial species, Atopobium spp., Bacteroides spp., Bacteroides vulgatus, Bacteroides acidifaciens, Bacteroides uniformis, Clostridium cocleatum, Clostridium xylanolyticum and Desulfovibrio spp., markedly increased in model mice, were positively correlated with LPS levels and pathophysiological features. Taken together, the results showed that the gut microbiota was altered significantly in the progression of liver disease. The connection between the gut microbial ecology and the liver pathology may represent potential targets for the prevention and treatment of chronic liver disease and HCC. 10.18632/oncotarget.8466
    The influence of gut microbiota on drug metabolism and toxicity. Li Houkai,He Jiaojiao,Jia Wei Expert opinion on drug metabolism & toxicology INTRODUCTION:Gut microbiota plays critical roles in drug metabolism. The variation of gut microbiota contributes to the interindividual differences toward drug therapy including drug-induced toxicity and efficacy. Accordingly, the investigation and elucidation of gut microbial impacts on drug metabolism and toxicity will not only facilitate the way of personalized medicine, but also improve rational drug design. AREAS COVERED:This review provides an overview of the microbiota-host co-metabolism on drug metabolism and summarizes 30 clinical drugs that are co-metabolized by host and gut microbiota. Moreover, this review is specifically focused on elucidating the gut microbial modulation of some clinical drugs, in which the gut microbial influences on drug metabolism, drug-induced toxicity and efficacy are discussed. EXPERT OPINION:The gut microbial contribution to drug metabolism and toxicity is increasingly recognized, but remains largely unexplored due to the extremely complex relationship between gut microbiota and host. The mechanistic elucidation of gut microbiota in drug metabolism is critical before any practical progress in drug design or personalized medicine could be made by modulating human gut microbiota. Analytical technique innovation is urgently required to strengthen our capability in recognizing microbial functions, including metagenomics, metabolomics and the integration of multidisciplinary knowledge. 10.1517/17425255.2016.1121234
    [Current situation and thinking on the intestinal microflora regulation with acupuncture and moxibustion]. Wang Wen-Yan,Liang Feng-Xia,Song Ai-Qun,Huang Qi,Chen Rui Zhen ci yan jiu = Acupuncture research Large number of microflora is parasitized in the human intestinal tract, which maintains the stability of the microecological environment in the host's intestinal tract and the healthy state of the body. Once the steady state is out of balance, the intestinal microflora is dysfunctional and a variety of diseases will be induced. Acupuncture and moxibustion have a positive role in improving different types of clinical problems by regulating , harmonizing and , and strengthening the body's resistance. At present, researches on the effect of acupuncture and moxibustion interventions on intestinal microflora mainly focuses on the following aspects 1) adjusting the count and proportion of the intestinal microflora to recover its stability, 2) improving gastrointestinal motility disorder by promoting the interaction between intestinal microflora and brain-gut axis (brain-gut peptides), and ameliorating the intestinal barrier function by reducing levels of proinflammatory cytokines to suppress inflammatory reactions. In the future, the research should pay more attention to the holistic regulatory function of acupuncture and moxibustion, the acupoint specificity, acupoint combination and different intervention measures, as well as the optimization of clinical regimen, so as to better intestinal microflora regulation. 10.13702/j.1000-0607.180118
    Similar connotation in chronic hepatitis B and nonalcoholic Fatty liver patients with dampness-heat syndrome. Dai Jianye,Sun Shujun,Cao Jianmei,Zhao Yu,Cao Huijuan,Zheng Ningning,Fang Junwei,Wang Yang,Zhang Wei,Zhang Yongyu,Hu Yiyang,Cao Zhiwei Evidence-based complementary and alternative medicine : eCAM The phenomenon that the same syndrome turns up in different diseases appears in the sight of people around the world, which raises the thought for possibility of "Same Treatment for Different Diseases." Actually, treatment based on ZHENG classification in Traditional Chinese Medicine could bring revelation for the former finding. The dampness-heat syndrome in chronic hepatitis B and nonalcoholic fatty liver is regarded as the breakthrough point. We discussed the molecular mechanism of similar connotation that exists in chronic hepatitis B and nonalcoholic fatty liver by metabonomics to give the modern understanding of dampness-heat syndrome. Both urine and serum metabolic profiling revealed that obvious differences existed between dampness-heat syndrome and non-dampness-heat syndrome but the commonality was proved to appear in chronic hepatitis B and nonalcoholic fatty liver patients with dampness-heat syndrome. Furthermore, disorder of body fluid metabolism, decline in digestive capacity, and imbalance of intestinal flora were found to be the new guiding for treatment, with the hope to provide the basis for Chinese personalized medicine. 10.1155/2013/793820
    Mechanistic Understanding of Herbal Therapy in Inflammatory Bowel Disease. Zhao Luqing,Zhang Shengsheng,He Peijian Current pharmaceutical design The incidence and prevalence of inflammatory bowel diseases (IBD), which comprise ulcerative colitis and Crohn's disease, are increasing dramatically worldwide. Immunomodulators and biological agents can help but cause severe side effects in long-term use. As such, complementary and alternative medicine, in particular herbal remedy, is becoming more and more popular in the treatment of IBD patients. Many natural compounds have been used in clinical trials and some have been proven promising in IBD treatment. To achieve a better understanding of herbal therapy, researchers focus on understanding the underlying mechanisms by using experimental rodent models. The mechanism of the pathogenesis of IBD is complex involving both environmental and genetic factors. IBD is considered as a consequence of impaired epithelial barrier function, gut microbiota dysbiosis, and aberrant immune response. Studies have demonstrated that herbal medicine can improve epithelial proliferation and barrier integrity, restore microbiota homeostasis, and suppress hyper-immune reaction. This review is to summarize current understanding of the molecular basis of herbal treatment of IBD at the levels of epithelial, microbial, and immune regulation. 10.2174/1381612823666171010124414
    Interaction between gut microbiota and ethnomedicine constituents. Wu Xue Ming,Tan Ren Xiang Natural product reports Covering: 2000 to 2018 (October) Trillions of microbes, collectively termed as gut microbiota, reside in the gastrointestinal tract and are involved in the physiology of their hosts. In humans, disease incidence and medical therapy are found to be associated with gut microbiota composition. Since ethnomedicines are largely plant-derived and orally ingested, this review summarizes the interactions of gut microbiota with ethnomedicine constituents (overwhelmingly, natural phytochemicals) to highlight the knowledge accumulation in (1) the modulation of the gut microbiota profile by ingested natural compounds, and (2) the gut microbial conversion of natural products into the 'daughter molecules' with potent bioactivities. By understanding such complex interactions of gut microbiota with ethnomedicines and/or the phytochemicals thereof, a fascinating frontier of natural-product chemistry may be substantially activated to conceptualize future therapeutic strategies. 10.1039/c8np00041g
    [Advance in studies on effect of Glycyrrhizae Radix et Rhizoma in relieving purgative activity of Rhei Radix et Rhizoma]. Su Bin,Li Xiao-bo Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica Rhei Radix et Rhizoma, as a commonly used traditional Chinese medicine, has been widely applied in clinic. Its major purgative constituent is anthraquinones, which are believed to be a toxic ingredient. Glycyrrhizae Radix et Rhizoma has been reputed as the best alexipharmic to moderate medicine natures. In this paper, the effect of Glycyrrhizae Radix et Rhizoma in relieving purgative activity of Rhei Radix et Rhizoma was studied in two aspects--the boiling process and intestinal metabolism; Studies on combined administration of Glycyrrhizae Radix et Rhizoma and Rhei Radix et Rhizoma in recent years were summarized according to chemical constituent, intestinal flora, I/II phase metabolism and drug transport. However, the material basis and mechanism for their compatibility remain unclear, further studies will be made in the future.
    Red Ginseng and Semen Coicis can improve the structure of gut microbiota and relieve the symptoms of ulcerative colitis. Guo Mingzhang,Ding Shuo,Zhao Changhui,Gu Xinxi,He Xiaoyun,Huang Kunlun,Luo Yunbo,Liang Zhihong,Tian Hongtao,Xu Wentao Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Many Chinese herbs are traditionally used as medicine to improve the functions of gastrointestinal tract. Some of these herbs are also promising agents for the improvement of the gut microbiota and the treatment of ulcerative colitis. MATERIALS AND METHODS:By screening seven traditional Chinese herbs, we found that Red Ginseng and Semen Coicis were the most effective in promoting the growth of probiotics including Lactobacillus and Bifidobacterium in vitro. We then evaluated the effects of Red Ginseng and Semen Coicis on the growth of the bacterial pathogens (Escherichia coli, Staphylococcus aureus, and Salmonella spp.) in vitro. In in vivo experiment, we gavage administrated trinitro-benzene-sulfonic acid induced ulcerative colitis (UC) rats with Red Ginseng and Semen Coicis extracts. After two weeks treatment, we analyzed the structure of the gut microbiota and examined the UC symptoms by employing qPCR and animal pathology detection techniques. RESULTS:Both Red Ginseng and Semen Coicis promoted the growth of probiotics - Bifidobacterium and Lactobacillus in vitro. Red Ginseng also inhibited the growth of some pathogen strains. In vivo, Red Ginseng and Semen Coicis improved the structure of gut microbiota and relieved the symptoms of ulcerative colitis in vivo. Compared with Semen Coicis, Red Ginseng was more effective in relieving the symptoms of ulcerative colitis. CONCLUSIONS:Red Ginseng could promote the growth of probiotic bacteria in vitro. Red Ginseng and, to a lesser extent Semen Coicis, gave positive results in an experimental in vivo model for ulcerative colitis. 10.1016/j.jep.2014.12.029
    A review of pharmacological and clinical studies on the application of Shenling Baizhu San in treatment of Ulcerative colitis. Ma Qianqian,Ouyang Yong,Meng Fansu,Noolvi Malleshappa N,Avvaru Stephen Paul,More Uttam A,Aminabhavi Tejraj M,Du Manling,Liu Hui,Zhuang Yong,Pang Mujuan,Cai Tiange,Cai Yu Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:The prescription of Shenling Baizhu San (SLBZS) was derived from the Song Dynasty "Taiping Huimin Heji Ju Fang", which was a representative prescription for treating spleen asthenic diarrhea. The prescription comprised of 10 herbs for treating weak spleen and stomach. It describes symptoms like eating less, loose stools, cough, shortness of breath and tired limbs. SLBZS has been reported to be capable of eliminating discomfort when it is administered for treating irritable bowel syndrome and diarrhea. This traditional Chinese medicine (TCM) formula has been widely used for improving gastrointestinal dysfunction and modifying the immune response to inflammation. AIM OF THE STUDY:This review is aimed to provide the up-to-date information on the pharmacology and clinical research of SLBZS in the treatment of ulcerative colitis (UC), and to discuss the research findings and possible deficiencies, hoping to better guide the clinical application and scientific research of SLBZS in the treatment of UC. MATERIALS AND METHODS:Relevant studies from 2004 to 2018 on SLBZS in the treatment of UC mechanism and curative effect were collected from ancient books, pharmacopoeia, reports, thesis via library and Digital databases (PubMed, CNKI, Google Scholar, Web of Science, SciFinder, Springer, Elsevier, etc). RESULTS:SLBZS could regulate inflammatory factors and intestinal flora, and ERK/p38 MAPK signaling pathway may be one of its targets. In addition, clinical research results show that SLBZS has a good therapeutic effect on UC, and the adverse reactions are small. CONCLUSION:Although SLBZS has achieved some success in the treatment of UC, there are still some scientific gaps. There is a lack of uniform standards for constructing UC animal models, and some methods of modeling through environmental and dietary interventions are not reproducible, and there is a lack of uniform dosing regimen standards. SLBZS doses follow the tradition and lack toxicological validation. Therefore, more specific toxicological research models are essential. The clinical application of SLBZS requires reassessment and standardization. Although all clinical research reports randomly assigned patients to different groups, most did not describe a detailed method of randomization and no description of the analysis data. In addition, extensive in vitro studies and further in-depth molecular studies are essential for the determination of mechanisms that have been performed in all in vivo experiments on animal models and patients. 10.1016/j.jep.2019.112105
    Integrative metabolic and microbial profiling on patients with Spleen-yang-deficiency syndrome. Lin Zhang,Ye Wu,Zu Xianpeng,Xie Haisheng,Li Houkai,Li Yiping,Zhang Weidong Scientific reports Gut microbiota is recognized as an indispensable "metabolic organ" that plays crucial roles in maintaining human health or initiating diseases. Spleen-yang-deficiency syndrome (SYDS) is a common syndrome of Traditional Chinese Medicine (TCM) clinic. It is a complex phenotype reflecting the overall changes of metabolism which are mainly caused by digestive disorders. However, little is known about the changes of gut microbiota and metabolism in patients with SYDS, as well as the crosstalk between gut microbiota and host metabolism. In the current study, an integrative metabolic and microbial profiling was performed on plasma, urine and feces from recruited SYDS and healthy individuals by using a LC-QTOFMS-based metabolomic and 16 s rRNA sequencing approaches. Our results showed a potentially significant contribution of gut dysbiosis to the metabolic disorders in SYDS. By integrating the differential gut bacteria with the metabolites, the results revealed some active bacterium of norank_f_CFT112H7, f_lachnospiraceae and bacteroides were closely involved in host mucosal integrity, bile acid metabolism and polysaccharides decomposition. Therefore, our results indicated the probable involvement of gut microbiota in mediating the metabolic changes, which warrants a further investigation on the role of gut microbiota in modulating the pathogenesis of SYDS. 10.1038/s41598-018-24130-7
    The roles of the TLR/NF‑κB signaling pathway in the mutual interactions between the lung and the large intestine. Fu Wen,Zhao Jing,Liu Xinglong,Gao Yongxiang,Zheng Chuan Molecular medicine reports The 'exterior-interior relationship between the lung and the large intestine' is a classical basic theory in Traditional Chinese Medicine. The present study aimed to investigate the roles of the toll like receptor/nuclear factor‑κB (TLR/NF‑κB) signaling pathway in the mutual interactions between the lung and the large intestine. A rat model of allergic asthma complicated with intestinal flora disorder was established by oral administration of Candida albicans and intraperitoneal injection with ovalbumin. The number of inflammatory cells and expression levels immunoglobulin (Ig)E, secretory IgA, interleukin (IL)‑4 and interferon‑γ in serum and bronchoalveolar lavage fluid were subsequently measured. Bacterial colonies and expression of 16S ribosomal DNA were studied in feces samples and pathological alterations of lung tissues were identified. Furthermore, the expression levels of genes associated with the TLR/NF‑κB signaling pathway in the lung and intestinal tissues were determined by reverse transcription‑quantitative polymerase chain reaction. The results of the present study indicated that, in the rat model of allergic asthma complicated with intestinal flora disorder, the expression levels of IL‑4 and IgE, and the numbers of inflammatory cells and C. albicans increased, and marked inflammatory cell infiltration was observed in lung tissues, suggesting that the animal model was successfully established. Furthermore, the present results revealed the mRNA expression levels of genes associated with the TLR/NF‑κB signaling (including myeloid differentiation primary response 88, TNF receptor associated factor 6 and β‑arrestin) were upregulated in both of the lung and intestinal tissues of the model group rats. Collectively, the results demonstrated that the TLR/NF‑κB signaling may serve roles in the mutual interactions between the lung and the large intestine, and TLR and NF‑κB may be potential targets for the treatment of lung diseases complicated with intestinal disorders. 10.3892/mmr.2018.9111
    An orally administered magnoloside A ameliorates functional dyspepsia by modulating brain-gut peptides and gut microbiota. Xue Zhenzhen,Wu Changxun,Wei Junying,Xian Minghua,Wang Tingting,Yang Bin,Chen Min Life sciences AIMS:Functional dyspepsia (FD) is very common worldwide with a high prevalence of 10%-30%, and it becomes a heavy burden to patients because of its hard to be cured. In our previous study, phenylethanoid glycosides were found to exist in Houpo, a traditional Chinese medicine commonly used for the treatment of abdominal distention, pain and dyspepsia. In the present study, the effect of magnoloside A (MA), a main phenylethanoid glycoside in Houpo, on FD was firstly evaluated and its potential mechanism was concluded. MATERIALS AND METHODS:MA was orally administered consequently for 3 weeks, and its effect on a FD rat model established through transient neonatal gastric irritation and mature alternate-day fasting was tested. Levels of brain-gut peptides and inflammatory factors in blood or tissues were determined by ELISA methods. Meanwhile, the gut microbiota was analyzed by 16S rRNA gene sequencing and short chain fat acids were determined by GC/MS. KEY FINDINGS:MA exhibited anti-FD activities by fastening the delayed gut emptying rate of FD rat and increasing the levels of gastrin, motilin, and calcitonin gene related protein; and decreasing the levels of 5-hydroxytryptamine, nitric oxide synthase, and vasoactive intestinal peptide. On the other hand, MA can modulate the composition of gut microbiota, resulting in the variation of the short chain fat acids. SIGNIFICANCE:MA ameliorated FD rats by modulating of the secretion of related brain-gut peptides and altering the composition of intestinal microbiota. 10.1016/j.lfs.2019.116749
    Euphorbia kansui fry-baked with vinegar modulates gut microbiota and reduces intestinal toxicity in rats. Jiang Dongjing,Kang An,Yao Weifeng,Lou Jianwei,Zhang Qiao,Bao Beihua,Cao Yudan,Yu Sheng,Guo Sijia,Zhang Yi,Tang Yuping,Zhang Li Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Euphorbia kansui (EK), a kind of toxic traditional Chinese medicine (TCM), is used in the treatment of edema, ascites and asthma. EK fry-baked with vinegar (VEK) is regularly used to reduce the toxicity in TCM. Previous studies have confirmed that fry-baking with vinegar could significantly reduce the significant gastrointestinal toxicity of EK. The toxic side-effects of EK are closely associated with intestinal tract, but existing research results could not provide practical measures for detoxification in terms of the biological effects of EK fry-baked with vinegar. AIM OF THE STUDY:This study aimed to investigate the gastrointestinal toxicity of EK and detoxification of VEK through the regulation of gut microbiota. Thirty male Sprague Dawley (SD) rats were randomly divided equally into 3 groups and received by oral gavage 0.5% CMC-Na (C group), EK (EKC group) or VEK (VEKC group) powder at 680 mg/kg for seven consecutive days. RESULTS:The ten toxic components in VEK were reduced significantly compared with those in EK. After fry-baked with vinegar, those side effects associated with VEK were significantly relieved in terms of histopathology and inflammatory injury indices of intestinal tissues, liver function and oxidative damage indices. The toxicity of EK might be highly correlated with Lactobacillus and Blautia genera. In addition, EK fry-baked with vinegar increased the production of short-chain fatty acids (SCFAs), which are regulated by gut microbiota. CONCLUSIONS:The proportion of main probiotics increased and potentially pathogenic bacteria decreased after EK was fry-baked with vinegar. It turned out that effective detoxification could be achieved by fry-baking with vinegar. 10.1016/j.jep.2018.07.029
    Isoliquiritigenin decreases the incidence of colitis-associated colorectal cancer by modulating the intestinal microbiota. Wu Minna,Wu Yaqi,Deng Baoguo,Li Jinsong,Cao Haiying,Qu Yan,Qian Xinlai,Zhong Genshen Oncotarget Imbalances in intestinal bacteria correlate with colitis-associated colorectal cancer (CAC). Traditional Chinese medicines have been used to adjust the gut microbiota, and isoliquiritigenin (ISL), a flavonoid extracted from licorice, has shown antitumor efficacy. In this study, the effects of ISL on CAC development and the gut microbiota were evaluated using an azoxymethane and dextran sulphate sodium (AOM/DSS)-induced mouse model of CAC (CACM). Histopathological analysis suggested that ISL reduced tumor incidence in vivo. Moreover, high-throughput sequencing and terminal restriction fragment length polymorphism (T-RFLP) studies of the bacterial 16S rRNA gene revealed that the structure of the gut microbial community shifted significantly following AOM/DSS treatment, and that effect was alleviated by treatment with high-dose ISL (150 mg/kg). Compared to the microbiota in the control mice (CK), the levels of Bacteroidetes decreased and the levels of Firmicutes increased during CAC development. ISL reversed the imbalance at the phylum level and altered the familial constituents of the gut microbiota. Specifically, the abundance of Helicobacteraceae increased after treatment with high-dose ISL, while the abundance of Lachnospiraceae and Rikenellaceae decreased. At the genus level, ISL reduced the abundance of opportunistic pathogens (Escherichia and Enterococcus), and increased the levels of probiotics, particularly butyrate-producing bacteria (Butyricicoccus, Clostridium, and Ruminococcus). Thus, ISL protects mice from AOM/DSS-induced CAC, and ISL and the gut microbiota may have synergistic anti-cancer effects. 10.18632/oncotarget.13347
    ZiBuPiYin recipe improves cognitive decline by regulating gut microbiota in Zucker diabetic fatty rats. Gu Chunyan,Zhou Wen,Wang Wang,Xiang Hong,Xu Huiying,Liang Lina,Sui Hua,Zhan Libin,Lu Xiaoguang Oncotarget Numerous researches supported that microbiota can influence behavior and modulate cognitive function through "microbiota-gut-brain" axis. Our previous study has demonstrated that ZiBuPiYin recipe (ZBPYR) possesses excellent pharmacological effects against diabetes-associated cognitive decline. To elucidate the role of ZBPYR in regulating the balance of gut microbiota to improve psychological-stress-induced diabetes-associated cognitive decline (PSDACD), we compared blood glucose, behavioral and cognitive functions and diversity of the bacterial community among experimental groups. The Zucker diabetic fatty (ZDF) rats with PSDACD exhibited behavioral and cognitive anomalies showing as increased anxiety- and depression-like behaviors and decreased learning and memory abilities. High-throughput sequencing of the bacterial 16S rRNA gene revealed that Roseburia and Coprococcus were decreased in ZDF rats with PSDACD compared with control group. Notably, these changes were reversed by ZBPYR treatment. Our findings indicate that ZBPYR might prevent PSDACD by maintaining the compositions of gut microbiota, which could be developed as a new therapy for T2D with PSDACD. 10.18632/oncotarget.14611
    Inhibition effect of glycyrrhiza polysaccharide (GCP) on tumor growth through regulation of the gut microbiota composition. Zhang Xiaoyu,Zhao Shuwu,Song Xinbo,Jia Jianwei,Zhang Zhaiyi,Zhou Huifang,Fu Hui,Cui Huantian,Hu Shuo,Fang Minjie,Liu Xiaomin,Bian Yuhong Journal of pharmacological sciences Glycyrrhiza Uralensis Polysaccharide (GCP), as a macromolecular polysaccharide extracted from the Traditional Chinese Medicine (TCM) - Licorice has been proved to inhibit tumor growth in vitro and in vivo; however, the specific anti-tumor mechanism of GCP needs to be further investigated. In this study, we explore the anti-tumor mechanism of GCP from the angle of gut microbiota. Colon carcinoma cells (CT-26) were used to set up a tumor-bearing mouse model. After 14 days of GCP treatment, the weights of tumors were significantly reduced. In addition, HE staining of tissue sections reflected that GCP could effectively inhibit tumor metastasis. 16SrRNA high-throughput sequencing of fecal samples showed a significant change between the model group and GCP group in the composition of gut microbiota. Subsequently, gut microbiota depletion and fecal transplantation experiments further confirmed the relationship between the anti-tumor effects of GCP and gut microbiota. Following depletion of gut microbiota, GCP cannot inhibit tumor growth. Fecal transplantation experiments found that transplanting the feces of GCP-treated mice, to a certain extent, could inhibit tumor growth and metastasis. These results indicate that Glycyrrhiza Polysaccharides exert anti-tumor effects by affecting gut microbiota composition. 10.1016/j.jphs.2018.03.006
    Canmei Formula Reduces Colitis-Associated Colorectal Carcinogenesis in Mice by Modulating the Composition of Gut Microbiota. Zhang Huayue,Hui Dengcheng,Li Yuan,Xiong Guangsu,Fu Xiaoling Frontiers in oncology The gut microbiota, including pathogenic microorganisms and probiotics, has been involved in tumor initiation and progression by regulating the components of intestinal flora. Canmei formula (CMF), a traditional Chinese medicine, chronicled in the Chuang Yang Jing Yan Quan Shu, has been clinically used as an adjuvant therapy to treat patients with colorectal carcinoma (CRC) in China. In this study, we investigate the treatment effect of CMF in the azoxymethane (AOM) and dextran sodium sulfate (DSS) induced and high-fat diet augmented colitis-associated colorectal cancer , and explore its mechanism of action. We found that CMF treatment relieved the inflammation and alteration of the gut microbiota and significantly inhibited the development of intestinal adenoma. Linear discriminant analysis showed that the flora diversity in the normal mice, model mice and CMF treatment mice was different. At the family level, the relative abundance of Desulfovibrionaceae decreased in CMF groups. The relative abundance of Desulfovibrionaceae were lower in the CMF groups than in model group, whereas Rikenellaceae and Alistipes were increased. Altogether our results indicate that CMF treatment ameliorate colitis-associated colorectal carcinogenesis by modulating the composition of the gut microbiota . 10.3389/fonc.2019.01149
    Structural modulation of gut microbiota during alleviation of antibiotic-associated diarrhea with herbal formula. Lv Weijie,Liu Cui,Ye Chunxin,Sun Jiaqi,Tan Xiaowen,Zhang Chao,Qu Qian,Shi Dayou,Guo Shining International journal of biological macromolecules The gut microbiome is hypothesized to play a critical role in gastrointestinal diseases, including antibiotic-associated diarrhea (AAD). To determine whether the traditional Chinese herbal formula of Shen Ling Bai Zhu San (SLBZS) modulates the composition of the gut microbiome during AAD treatment, an AAD diarrhea model was prepared in rats by gastric gavage with lincomycin for 7 successive days, followed by administration of SLBZS for one week. At all time points after the SLBZS treatment, the diarrhea rates were significantly or at least numerically lower than that of the untreated model group. Overall structural modulation of the gut microbiome occurred after SLBZS treatment, with reverting effects on the AAD-induced structural variations. At the genus level, the relative abundance of Sutterella was negatively correlated with SLBZS treatment and positively correlated with a lack of treatment, suggesting that Sutterella might be a pivotal phylotype associated with the improvement of AAD. The key phylotypes of the gut microbiome that responded to SLBZS indicated enrichment of beneficial bacteria, and particularly Bacteroides spp. These data therefore demonstrated that structural changes of the gut microbiome are induced by the Chinese herbal formula SLBZS. In conclusion, changes in the gut microbiome are associated with the diarrhea-controlling effect of SLBZS. 10.1016/j.ijbiomac.2017.02.060
    Gancao-Gansui combination impacts gut microbiota diversity and related metabolic functions. Yu Jingao,Guo Jianming,Tao Weiwei,Liu Pei,Shang Erxin,Zhu Zhenhua,Fan Xiuhe,Shen Juan,Hua Yongqing,Zhu Kevin Yue,Tang Yuping,Duan Jin-Ao Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:The theory of "eighteen incompatible medicaments" (EIM) in traditional Chinese medicine (TCM) is the most representative case of herbal-herbal interactions. Gancao and Gansui are one of the incompatible herbal pairs in EIM. Gancao, also known as "licorice", is the most frequently used Chinese herb or food additive. Gansui, the root of Euphorbia kansui T.P. Wang, is another famous Chinese herb usually used to treat edema, ascites and asthma but could induce gastrointestinal (GI) tract irritation. Although Gancao and Gansui are incompatible herbal pairs, they are still used in combination in the famous "Gansui-Banxia" decoction. AIM OF THE STUDY:This study was conducted to investigate if Gancao-Gansui combination could exacerbate Gansui induced GI tract injury. Moreover, the impact of Gancao-Gansui combination to gut microbiota and related metabolism pathways were evaluated. MATERIALS AND METHODS:Normal mice were divided into different groups and treated with Gancao extracts, Gansui extracts, and Gancao-Gansui combination extracts for 7 days. Serum biomarkers (diamine oxidase activity, lipopolysaccharide, motilin, IL-1β, IL-6, TNF-α) were determined to reflect GI tract damage. Gut microbiota diversity was studied by 16S rDNA sequencing and metagenomes analysis were also conducted to reflect functional genes expression alteration. Fecal hydrogen sulfide concentrations were measured by spectrophotometry to confirm the alteration of Desulfovibrio genus. Fecal lipid metabolomics study was conducted by GC-MS analysis to confirm the change of metagenomes and Mycoplasma abundance. RESULTS:Gancao-Gansui combination did not exacerbate GI tract tissue or functional damage but caused gut microbiota dysbiosis and increased some rare genus's abundance including Desulfovibrio and Mycoplasma. Desulfovibrio genus proliferation was confirmed by the disturbance of fecal hydrogen sulfide homeostasis. Gancao-Gansui combination also dys-regulated the metabolic genes in metagenomes. Mycoplasma genus proliferation and the metagenomes changes were both confirmed by metabolic profile analysis of fecal lipids, especially cholesterol. CONCLUSIONS:Gancao-Gansui combination can impact the gut microbiota diversity and related metabolic functions. Further studies should be carried out when the combination of Gancao-Gansui is used in herbal formulations as this may alter the diversity of the microbiota. 10.1016/j.jep.2017.11.031
    Rhubarb Peony Decoction ameliorates ulcerative colitis in mice by regulating gut microbiota to restoring Th17/Treg balance. Luo Shuang,Wen Ruyan,Wang Qing,Zhao Zhongxiang,Nong Feifei,Fu Yajun,Huang Shaowei,Chen Jinyan,Zhou Lian,Luo Xia Journal of ethnopharmacology ETHNOPHARMACOLOGY RELEVANCE:Rhubarb Peony Decoction (RPD) is a formula of traditional Chinese medicine chronicled in Jin Gui Yao Lve, commonly used to treat ulcerative colitis (UC). However, the underlying mechanism of RPD treating UC remains elusive. In our study, we investigated the therapeutic efficacy of RPD and potential mechanism involved in inhibiting dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. METHODS:The colitis was induced by DSS in mice for 5 days and estimated body weight loss, disease activity index (DAI) and colon length. Histological changes were observed by H&E staining. The number and abundance of gut mircrobiota were measured with 16 S rDNA sequencing. GC-MS was used to detect the concentration of short chain fatty acids (SCFAs) in cecum. Flow cytometry analyzed the proportion of Th17 and Treg cells in mesenteric lymph nodes (MLNs). IL-17A and Foxp3 in colon were determined by immunohistochemical analyses. The level of cytokine was determined by Multi-Analyte Flow Assay Kit. RESULTS:Administration of RPD significantly alleviated the pathological changes of UC mice, involving rescued the inflammation-related reduction of colon length, ameliorated body weight loss and damaged tissue. In addition, RPD altered the gut microbiota, involving restored α diversity, increased significantly the abundance of Firmicutes and Actinobacteria, decreased the Proteobacteria and Bacteroidetes. Furthermore, the number of Butyricicoccus pullicaecorum, a butyrate-producing bacterium, were augmented obviously by RPD. Besides, RPD restored the content of SCFA in intestinal tract. Additionally, the proportion of Th17 cells and Treg cells in mesenteric lymph nodes, likewise, the expression of IL-17A and Foxp3 in colon were regulated by RPD, contributing to the restoration of Th17/Treg balance. Moreover, RPD significantly decreased the level of IL-6, TNF-α, IFNγ, IL-10, IL-17A, IL-21, IL-22 in colon, simultaneously increased Treg-related cytokine TGF-β at dose-dependently. CONCLUSIONS:These results demonstrated that RPD had effect on ulcerative colitis, which was related to regulating gut microbiota, especially Butyricicoccus pullicaecorum, and SCFAs to restore the gut Th17/Treg homeostasis. 10.1016/j.jep.2018.08.033
    Effects of acupuncture in treating insomnia due to spleen-stomach disharmony syndrome and its influence on intestinal microbiome: Study protocol for a randomized controlled trial. Huangfu Ya-Ru,Peng Wei,Guo Bao-Jun,Shen Zhi-Fu,Li Li,Liu Shi-Wei,Zheng Hui,Hu You-Ping Journal of integrative medicine BACKGROUND:Insomnia is a common complaint that is closely related to gastrointestinal symptoms, which is consistent with the traditional Chinese medicine classical theory of "stomach disharmony leading to restless sleep." Acupuncture is an effective complementary and alternative medicine therapy to improve gastrointestinal function and restore the normal sleep-wake cycle. However, studies on the effectiveness of acupuncture for insomnia due to spleen-stomach disharmony syndrome are limited to case reports and few randomized controlled trials; deeper research on its mechanism is still lacking. This randomized controlled trial aims to assess the treatment efficacy of "harmonizing stomach to tranquilize mind" acupuncture for insomnia and its influence on the intestinal microbiome. METHODS/DESIGN:This is a randomized, single-blind, parallel-group study. Sixty eligible patients with insomnia due to spleen-stomach disharmony syndrome will be randomly divided into two groups (1:1 allocation ratio). The intervention group will use "harmonizing stomach to tranquilize mind" acupuncture, and the control group will receive sham acupuncture. Participants will receive 5 acupuncture treatment sessions per week for 4 consecutive weeks. The Pittsburgh Sleep Quality Index will be used to evaluate the clinical efficacy of acupuncture treatment by making assessments at baseline, the end of treatment and the end of the follow-up. High-throughput 16S ribosomal ribonucleic acid gene sequencing will be performed to detect changes in the intestinal microbial composition before and after treatment. DISCUSSION:The results of this trial are expected to confirm that "harmonizing stomach to tranquilize mind" acupuncture can effectively relieve insomnia and alter the intestinal microbiome. TRIAL REGISTRATION:Chinese Clinical Trials Registry: ChiCTR1800017092. 10.1016/j.joim.2019.01.007
    The anti-diabetic activities, gut microbiota composition, the anti-inflammatory effects of Scutellaria-coptis herb couple against insulin resistance-model of diabetes involving the toll-like receptor 4 signaling pathway. Zhang Chang-Hua,Sheng Jun-Qing,Sarsaiya Surendra,Shu Fu-Xing,Liu Tong-Tong,Tu Xiu-Ying,Ma Guang-Qiang,Xu Guo-Liang,Zheng Hong-Xiang,Zhou Li-Fen Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Scutellaria-coptis herb couple (SC) is one of the well-known herb couples in many traditional Chinese compound formulas used for the treatment of diabetes mellitus (DM), which has been used to treat DM for thousands of years in China. AIM OF THE STUDY:Few studies have confirmed in detail the anti-diabetic activities of SC in vivo and in vitro. The present investigations aimed to evaluate the anti-diabetic activity of SC in type 2 diabetic KK-Ay mice and in RAW264.7 macrophages to understand its possible mechanism. MATERIALS AND METHODS:High-performance liquid chromatography with ultraviolet detection (HPLC-UV) and LC-LTQ-Orbitrap Pro mass spectrometry were used to analyze the active ingredients of SC extracts and control the quality. A type 2 diabetic KK-Ay mice model was established by high-fat diet. Body weight, fasting blood glucose levels, fasting blood insulin levels, glycosylated hemoglobin and glycosylated serum protein were measured. The effects of SC on total cholesterol (TC), high-density lipoprotein (HDL) and triglyceride (TG) levels were examined. The lipopolysaccharide (LPS), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) levels were measured. Gut microbial communities were assayed by polymerase chain reaction (PCR) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) methods. The expressions of Toll-like receptor 4 (TLR4) and MyD88 protein in the colons were measured by western blot. In RAW264.7 macrophages, IL-6, TNF-α, TLR4 and MyD88 protein levels were measured by enzyme-linked immunosorbent assay (ELISA) kits or western blot, and the mRNA expression of IL-6, TNF-α and TLR4 was examined by the real time PCR. RESULTS:The present results showed that the SC significantly increased blood HDL and significantly reduced fasting blood glucose, fasting blood insulin, glycosylated hemoglobin, glycosylated serum protein, TC, TG, LPS, IL-6 and TNF-α levels (P < 0.05 or P < 0.01) in type-2 diabetic KK-Ay mice. Furthermore, SC could regulate the structure of intestinal flora. Additionally, the expressions of TLR4 and MyD88 protein in the colons were significantly decreased in the model group (P < 0.05 or P < 0.01). However, SC had no significant effect on weight gain. In RAW264.7 macrophages, SC containing serum (SC-CS) (5%, 10% and 20%) significantly decreased IL-6, TNF-α, TLR4 and MyD88 protein levels and the mRNA expression of IL-6, TNF-α and TLR4 (P < 0.05 or P < 0.01). CONCLUSIONS:The anti-diabetic effects of SC were attributed to its regulation of intestinal flora and anti-inflammation involving the TLR4 signaling pathway. These findings provide a new insight into the anti-diabetic application for SC in clinical settings and display the potential of SC in the treatment of DM. 10.1016/j.jep.2019.02.040
    Effect of mild moxibustion on intestinal microbiota and NLRP6 inflammasome signaling in rats with post-inflammatory irritable bowel syndrome. Bao Chun-Hui,Wang Chun-Ye,Li Guo-Na,Yan Yi-Lu,Wang Di,Jin Xiao-Ming,Wu Lu-Yi,Liu Hui-Rong,Wang Xiao-Mei,Shi Zheng,Wu Huan-Gan World journal of gastroenterology BACKGROUND:About one-third of refractory irritable bowel syndrome (IBS) cases are caused by gastrointestinal (GI) infection/inflammation, known as post-infectious/post-inflammatory IBS (PI-IBS). Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS, whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear. AIM:To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS. METHODS:Sprague-Dawley rats were divided into a normal control group, a model control group, a mild moxibustion group, and a sham mild moxibustion group. PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu (ST 25) and Zusanli (ST36) for 7 consecutive days for 10 min each time. The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited. Abdominal withdrawal reflex (AWR) score was measured to assess the visceral sensitivity, and colon histopathology and ultrastructure, colonic myeloperoxidase (MPO) activity, and serum C-reactive protein (CRP) level were measured to evaluate low-grade colonic inflammation in rats. The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence, qRT-PCR, and Western blot. RESULTS:The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group. Mild moxibustion remarkably increased the relative DNA abundances of , , and but decreased that of in the gut of PI-IBS rats. Additionally, mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the expression of IL-1β, IL-18, and resistance-like molecule β by promoting the NLRP6 and reducing the mRNA and protein expression of apoptosis-associated speck-like protein containing CARD (ASC) and cysteinyl-aspartate-specific proteinase 1 (Caspase-1). The relative DNA abundances of , , , and in each group were correlated with the mRNA and protein expression of NLRP6, ASC, and Caspase-1 in the colon. CONCLUSION:These findings indicated that mild moxibustion can relieve low-grade GI inflammation and alleviate visceral hypersensitivity in PI-IBS by regulating intestinal microbes and controlling NLRP6 inflammasome signaling. 10.3748/wjg.v25.i32.4696
    Zengye decoction induces alterations to metabolically active gut microbiota in aged constipated rats. Liu Deliang,Lin Lei,Lin Yixuan,Zhong Yuping,Zhang Shaobao,Liu Wen,Zou Baorong,Liao Qiongfeng,Xie Zhiyong Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Zengye decoction (ZYD), a traditional Chinese medicinal formula, has been used in the treatment of various chronic diseases, such as constipation and skin dryness syndrome. Clinically, the specific mechanisms and targets of ZYD for treating disease remain unclear. The present study was undertaken to investigate the effects of ZYD on the gut microbiota and host metabolites in aged constipated rats and the relationship between the intestinal microbiota and the host. Rats were divided randomly into three groups, the control group (n = 10), recovery group (n = 10) and ZYD group (n = 10). First, the aged constipation model was established for the ZYD group and recovery group. Then, rats in the ZYD group were treated with ZYD. Urinary and faecal samples of each animal were collected in microcentrifuge tubes. Next, 16s rRNA gene sequencing was employed to analyse the composition of the gut microbiome in faecal samples and afterwards the metabolic function of the altered gut microbiota was predicted. Additionally, H NMR profiling was used to detect the alterations of host metabolites in urine and faecal samples to verify the metabolic function results obtained from sequencing. As a result, ZYD reduced the level of harmful bacteria, such as Desulfovibrio, Ruminococcus, Prevotella and Dorea, and increased the abundance of Oxalobacter, Clostridium and Roseburia. The functional prediction of changes in the gut microbiota induced by ZYD revealed that ZYD promoted energy storage, regulated amino acid metabolism, inhibited methane metabolism, strengthened the physiological function of glutathione and reduced bacterial toxin. The H NMR profiles revealed that ZYD regulated the carbohydrates, short chain fatty acids, amino acids and amines in the aged constipated rats. In addition, most metabolic changes observed were related to the function of intestinal microbiota. These results suggest that ZYD can regulate the intestinal microbiota of constipated rats to normal levels and change the endogenous metabolites of the host through the intestinal microbiota to achieve therapeutic effects. 10.1016/j.biopha.2018.11.013
    Xiaoyaosan improves depressive-like behavior in rats with chronic immobilization stress through modulation of the gut microbiota. Zhu Hui-Zheng,Liang Yu-Dan,Ma Qing-Yu,Hao Wen-Zhi,Li Xiao-Juan,Wu Man-Si,Deng Li-Juan,Li Yu-Ming,Chen Jia-Xu Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Depression has become the leading cause of disability worldwide and a growing public health problem in China. In addition, intestinal flora may be associated with depression. This study investigated the effect of the decoction Xiaoyaosan (XYS) against depressive behavior through the regulation of intestinal flora. Fifty-two healthy male Sprague-Dawley rats were randomly divided into four groups (i.e., control, model, XYS, and fluoxetine). The latter three groups were subjected to 21 days of chronic restraint stress to produce the stress depression model. Rats in the XYS and fluoxetine groups received intragastric administration of XYS and fluoxetine, respectively. The behavioral changes of the rats were observed after 21 days. Stool specimens were sequenced using the 16S rDNA high-throughput method to detect the structure and changes in intestinal flora. There was no difference observed in alpha diversity among the groups. At the phylum level, XYS regulated the abundance of Bacteroidetes, Proteobacteria, Firmicutes, Chloroflexi, and Planctomycetes. At the genus level, XYS reduced the abundance of the Prevotellaceae_Ga6A1_group, Prevotellaceae_UCG-001, and Desulfovibrio. On the contrary, it increased the abundance of the Ruminococcaceae family to improve depression-like behavior. The mechanism involved in this process may be related to short-chain fatty acids, lipopolysaccharides, and intestinal inflammation. 10.1016/j.biopha.2019.108621
    Human Gut Microbiota and Gastrointestinal Cancer. Meng Changting,Bai Chunmei,Brown Thomas D,Hood Leroy E,Tian Qiang Genomics, proteomics & bioinformatics Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment. 10.1016/j.gpb.2017.06.002
    Characteristics of gut microbiota and its response to a Chinese Herbal Formula in elder patients with metabolic syndrome. Ni Yongcheng,Mu Chunlong,He Xiangyu,Zheng Kaiming,Guo Hongmin,Zhu Weiyun Drug discoveries & therapeutics Alterations in gut microbiota have been known to play a critical role in metabolic syndrome. However, the microbial features in elderly patients with metabolic syndrome remain unclear. A traditional Chinese Herbal Formula, Yangyin Tiluo Decoction (YTD), can alleviate metabolic syndrome and cardiovascular disease. To characterize gut microbiota in elder patients and effects of YTD on gut microbiota during treatment of metabolic syndrome, 11 healthy elderly persons and 12 elderly persons (aged 60-90 years) with metabolic syndrome were enrolled. The patients were randomly assigned to receive YTD for 4 weeks (200 mL of the decoction two times daily). The microbial composition in healthy control, pre- and post- YTD treatment group were analyzed by 16S rRNA sequencing of fecal DNAs. Biochemical measurements were conducted for elderly patients. The results showed a high inter-individual variation of gut microbiota in elderly persons. The gut microbiota was dominated by phylum Firmicutes and Actinobacteria, which was distinct from the previously defined microbiota in Irish elderly persons. The elderly patients with metabolic syndrome had higher proportions of Lactobacillus and Bifidobacterium, and lower proportions of Anaerostipes, Coprococcus, Ruminococcus than healthy controls. YTD treatment reduced the abundance of genus Bacteroidales Incertae Sedis and species Enterobacteriaceae Incertae Sedis. The concentration of plasma lipoprotein (a) was also reduced, which was negatively correlated with the abundance of an Acinetobacter species. These results reveal a remarkable dominance of Firmicutes and Actinobacteria, and highlight the distinct gut microbiota in elderly patients with metabolic syndrome, which may be involved in pathogenesis. Furthermore, the benefits of YTD treatment were observed, providing an approach to improve metabolic syndrome in elderly patients. 10.5582/ddt.2018.01036
    Moxibustion inhibits interleukin-12 and tumor necrosis factor alpha and modulates intestinal flora in rat with ulcerative colitis. Wang Xiao-Mei,Lu Yuan,Wu Lu-Yi,Yu Shu-Guang,Zhao Bai-Xiao,Hu Hong-Yi,Wu Huan-Gan,Bao Chun-Hui,Liu Hui-Rong,Wang Jin-Hai,Yao Yi,Hua Xue-Gui,Guo Hui-Ying,Shen Li-Rong World journal of gastroenterology AIM:To investigate the effect of moxibustion on intestinal flora and release of interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α) from the colon in rat with ulcerative colitis (UC). METHODS:A rat model of UC was established by local stimulation of the intestine with supernatant from colonic contents harvested from human UC patients. A total of 40 male Sprague-Dawley rats were randomly divided into the following groups: normal (sham), model (UC), herb-partition moxibustion (HPM-treated), and positive control sulfasalazine (SA-treated). Rats treated with HPM received HPM at acupuncture points ST25 and RN6, once a day for 15 min, for a total of 8 d. Rats in the SA group were perfused with SA twice a day for 8 d. The colonic histopathology was observed by hematoxylin-eosin. The levels of intestinal flora, including Bifidobacterium, Lactobacillus, Escherichia coli (E. coli), and Bacteroides fragilis (B. fragilis), were tested by real-time quantitative polymerase chain reaction to detect bacterial 16S rRNA/DNA in order to determine DNA copy numbers of each specific species. Immunohistochemical assays were used to observe the expression of TNF-α and IL-12 in the rat colons. RESULTS:HPM treatment inhibited immunopathology in colonic tissues of UC rats; the general morphological score and the immunopathological score were significantly decreased in the HPM and SA groups compared with the model group [3.5 (2.0-4.0), 3.0 (1.5-3.5) vs 6.0 (5.5-7.0), P < 0.05 for the general morphological score, and 3.00 (2.00-3.50), 3.00 (2.50-3.50) vs 5.00 (4.50-5.50), P < 0.01 for the immunopathological score]. As measured by DNA copy number, we found that Bifidobacterium and Lactobacillus, which are associated with a healthy colon, were significantly higher in the HPM and SA groups than in the model group (1.395 ± 1.339, 1.461 ± 1.152 vs 0.045 ± 0.036, P < 0.01 for Bifidobacterium, and 0.395 ± 0.325, 0.851 ± 0.651 vs 0.0015 ± 0.0014, P < 0.01 for Lactobacillus). On the other hand, E. coli and B. fragilis, which are associated with an inflamed colon, were significantly lower in the HPM and SA groups than in the model group (0.244 ± 0.107, 0.628 ± 0.257 vs 1.691 ± 0.683, P < 0.01 for E. coli, and 0.351 ± 0.181, 0.416 ± 0.329 vs 1.285 ± 1.039, P < 0.01 for B. fragilis). The expression of TNF-α and IL-12 was decreased after HPM and SA treatment as compared to UC model alone (4970.81 ± 959.78, 6635.45 ± 1135.16 vs 12333.81 ± 680.79, P < 0.01 for TNF-α, and 5528.75 ± 1245.72, 7477.38 ± 1259.16 vs 12550.29 ± 1973.30, P < 0.01 for IL-12). CONCLUSION:HPM treatment can regulate intestinal flora and inhibit the expression of TNF-α and IL-12 in the colon tissues of UC rats, indicating that HPM can improve colonic immune response. 10.3748/wjg.v18.i46.6819
    Research on mechanism of charred hawthorn on digestive through modulating "brain-gut" axis and gut flora. Wang Yun,Lv Min,Wang Ting,Sun Jingying,Wang Yuxia,Xia Manqiong,Jiang Yun,Zhou Xia,Wan Jun Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Hawthorn is a traditional Chinese medicine for high-calorie-diet-induced dyspepsia (HC-DID) for thousands of years old. Based on traditional Chinese medicine (TCM) theory and clinical and non-clinical trials, its stir-frying processed product, charred hawthorn, possesses better effect. At present, most research mainly focuses on chemical constituents of hawthorn before and after stir-frying process, but there is no relevant action-mechanism study about fragrant odor promoting HC-DID during the stir-frying process of the hawthorn. AIM OF THE STUDY:The purpose of the present study is to research on mechanism of hawthorn decoction coupled with odor of charred hawthorn on digestive in rats with HC-DID. MATERIALS AND METHODS:The SPF Kunming (KM) mice and Sprague Dawley (SD) rats were randomly divided into 7 groups: control group, model group, cisapride group, hawthorn group (HT), charred hawthorn group (CHT), odor of charred hawthorn (OCHT), CHT + OCHT group. The rats were modeled as HC-DID, whose treatment by intragastric administration and odor administration. Obvious symptoms of HC-DID were observed. Gastrointestinal motility were detected. Histopathology was performed in hypothalamus and gastrointestinal tract. Related brain-gut peptides were assayed in serum, hypothalamus and gastrointestinal tract. Illumina Miseq platform was used for 16S rDNA high-throughput sequencing to detect the intestinal flora structure of the caecum of rats. RESULTS:Traditional Chinese medicine decoction of hawthorn (HT and CHT) regulated the body weight, food intake, gastrointestinal motility and abnormal secretion of brain-gut peptides in rats with HC-DID, and the odor of charred hawthorn also had good curative effect for it. Moreover, the intestinal dysbiosis was induced by high-calorie diet in rats with dyspepsia, and hawthorn decoction could ease this trend. CONCLUSION:The above study showed that hawthorn decoction coupled with the odor of charred hawthorn effectively alleviate HC-DID in rats by regulating the "Brain-Gut" axis and gut flora. Odor treatment of hawthorn could be a potential therapeutic approach for HC-DID. 10.1016/j.jep.2019.112166
    Metabolism of constituents in Huangqin-Tang, a prescription in traditional Chinese medicine, by human intestinal flora. Zuo Feng,Zhou Zhong-Ming,Yan Mei-Zhen,Liu Mei-Lan,Xiong Yu-Lan,Zhang Qing,Song Hong-Yue,Ye Wen-Hua Biological & pharmaceutical bulletin In the course of studies on the metabolism of active components of Huangqin-Tang by human intestinal flora (HIF), Huangqin-Tang and all individual herbs in the decoctions were incubated with a human fecal suspension separately. By using a high-performance liquid chromatographic (HPLC) method which was previously established in our laboratory, the metabolites in both the compound prescription and all the single herb decoctions were identified and determined both qualitatively and quantitatively. We found that the constituents of Huangqin-Tang, incluing baicalin (baicalein 7-glucuronide; BG), wogonoside (wogoninoglucuronide; WG), oroxylin-A-glucuronide (OG) from Scutellariae Radix, paeoniflorin (PF) from Paeoniae Radix, liquiritin (liquiritigenin 4'-O-glucoside; LG), isoliquirtin (isoliquiritigenin 4-glucoside; ILG) and glycyrrhizic acid (GL) from Glycyhhizea Radix, were converted to their metabolites baicalein (B), wogonin (W), oroxylin-A (O), paeonimetabolin-I (PM-I), liquiritigenin (L), isoliquiritigenin (IL) and glycyrrhetinic acid (GA) by HIF. The contents of the metabolites in Huangqin-Tang and in each single herb decoction increased significantly after incubation with intestinal flora. Comparing with single herb decoctions, the transformation of BG, WG, OG, LG and ILG in the compound prescription was promoted, however, that of PF and GL was inhibited. All the results suggested that the glycosides of many medicinal herbs could be converted to aglycones by HIF, and the metabolism of most glycosides was improved in the compound prescription. 10.1248/bpb.25.558
    Effects of a homogeneous polysaccharide from Sijunzi decoction on human intestinal microbes and short chain fatty acids in vitro. Gao Beibei,Wang Ruijun,Peng Ying,Li Xiaobo Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Sijunzi decoction (SJZD) is a classic recipe in traditional Chinese medicine (TCM) to strengthen the spleen and replenish Qi. It is well known for treating disorders of gastrointestinal function manifested in poor appetite, reduced food intake and loose stools. Polysaccharide is the most abundant constituent and the major effective component in SJZD. AIM OF THE STUDY:The present study aimed to understand the immunomodulatory mechanism of S-3-1, a homogeneous polysaccharide purified from SJZD with immune-enhancement activity, by investigating its effects on human intestinal microbes and short chain fatty acids. MATERIALS AND METHODS:S-3-1 was incubated with simulated gastric juice, intestinal juice, and human fecal microflora independently and sequentially. The concentrations of total polysaccharide and reducing sugar were measured to identify the stability of independently and sequentially incubated S-3-1 in three in vitro fermentation models. Gas chromatograph (GC) analysis was used to measure the short chain fatty acid (SCFA) contents in human fecal samples. The human gut microbiota composition was measured by 16S rRNA gene Illumina MiSeq sequencing (V3-V4 region). RESULTS:S-3-1 was degraded in three in vitro fermentation models separately and sequentially. Both S-3-1 and incubated S-3-1 could regulate the abundances of Lactobacillus, Pediococcus, Streptococcus, Bacteroides, Enterococcus, Clostridium and Dorea in human intestinal microflora samples. Specifically, S-3-1 could only regulate the abundances of Paraprevotella and Oscillospira, while the influenced flora changed to Butyricimonas, Coprococcus, Dialister, Sutterella, Ruminococcus and Parabacteroides after sequential incubation of S-3-1. In contrast to S-3-1 showing no influence on the content of SCFA, incubated S-3-1 showed increased contents of acetic acid and total acid that were associated with its effects on the abundances of Enterococcus, Sutterella, Butyricimonas and Streptococcus. CONCLUSION:S-3-1 plays an immunomodulatory role by regulating the abundances of 9 intestinal bacteria genera. Incubated S-3-1 can regulate more bacteria genera, a total of 13 kinds, and can adjust the SCFA content to affect immunomodulation. Incubation with gastric and intestinal juices enhanced S-3-1's capability of modulating the intestinal flora composition and decreased the bacteria's need for a carbon source. This study could provide new insights for studies on the pharmacological mechanisms of polysaccharides in vitro. 10.1016/j.jep.2018.06.006
    Therapeutic effect of n-butanol fraction of Huang-lian-Jie-du Decoction on ulcerative colitis and its regulation on intestinal flora in colitis mice. Yuan Ziwen,Yang Lihong,Zhang Xiaosong,Ji Peng,Wei Yanming Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Huang-lian-Jie-du Decoction (HLJDD) is a classical prescription for clearing away heat and detoxification. In order to screen the effective fraction of HLJDD in the treatment of ulcerative colitis (UC) in mice and explore its effects on intestinal flora in UC mice, we prepared different polar fractions of HLJDD by system solvent extraction method. Subsequently, the contents of 13 active compounds in different polar fractions of HLJDD were determined by HPLC. Further, the UC model induced by dextran sodium sulfate was used to evaluate the therapeutic effects of different polar fractions of HLJDD. Finally, cecal contents were used for sequencing and analysis of bacterial 16S rRNA genes. The results showed that the yield of HLJDD-n-butanol (HLJDD-NBA) fraction was the highest, and the content or proportion of 13 active compounds in HLJDD-NBA fraction were the most similar to HLJDD. In addition, in vivo pharmacodynamic experiments showed that HLJDD-NBA intervention not only significantly alleviated the clinical symptoms of UC mice and ameliorated the pathological damage of colon tissue, but also showed significant anti-inflammatory and antioxidative effects (p < 0.05), which were comparable to HLJDD (p > 0.05). Moreover, both HLDD and HLJDD-NBA treatments can restore the intestinal flora homeostasis of UC mice by inhibiting the growth of intestinal pathogens and preventing the decrease of beneficial bacteria. Meanwhile, they can also significantly correct the dysfunction of intestinal flora in UC mice. In conclusion, we proved that HLJDD-NBA fraction is an effective fraction of HLJDD in treating UC in mice, and it can maintain the intestinal flora homeostasis of UC mice, which increases our understanding of the mechanism of HLJDD in treating UC and lays a foundation for the development of new anti-ulcer drugs. 10.1016/j.biopha.2019.109638
    16S rDNA analysis of the effect of fecal microbiota transplantation on pulmonary and intestinal flora. Liu Tianhao,Yang Zhongshan,Zhang Xiaomei,Han Niping,Yuan Jiali,Cheng Yu 3 Biotech This study aims to explore the effect of FMT on regulations of dysbacteriosis of pulmonary and intestinal flora in rats with 16S rDNA sequencing technology. A total of 27 SPF rats (3-4 weeks old) were randomly divided into three groups: normal control group (K), model control group (MX), and fecal microbiota transplantation group (FMT); each group contained nine rats. The OTU values of the pulmonary and intestinal flora of the MX group decreased significantly compared with the normal control group. After FMT, the OTU value of pulmonary flora increased, while the value of OTU in intestinal flora declined. At the phylum level, FMT down-regulated , , and in the pulmonary flora. At the genus level, FMT down-regulated , , , , and , thus maintaining the balance of the pulmonary flora. Moreover, FMT could change the structure and diversity of the pulmonary and intestinal flora by positively regulating the pulmonary flora and negatively regulating intestinal flora. This study may provide a scientific basis for FMT treatment of respiratory diseases. 10.1007/s13205-017-0997-x
    Targeting the human genome-microbiome axis for drug discovery: inspirations from global systems biology and traditional Chinese medicine. Zhao Liping,Nicholson Jeremy K,Lu Aiping,Wang Zhengtao,Tang Huiru,Holmes Elaine,Shen Jian,Zhang Xu,Li Jia V,Lindon John C Journal of proteome research Most chronic diseases impairing current human public health involve not only the human genome but also gene-environment interactions, and in the latter case the gut microbiome is an important factor. This makes the classical single drug-receptor target drug discovery paradigm much less applicable. There is widespread and increasing international interest in understanding the properties of traditional Chinese medicines (TCMs) for their potential utilization as a source of new drugs for Western markets as emerging evidence indicates that most TCM drugs are actually targeting both the host and its symbiotic microbes. In this review, we explore the challenges of and opportunities for harmonizing Eastern-Western drug discovery paradigms by focusing on emergent functions at the whole body level of humans as superorganisms. This could lead to new drug candidate compounds for chronic diseases targeting receptors outside the currently accepted "druggable genome" and shed light on current high interest issues in Western medicine such as drug-drug and drug-diet-gut microbial interactions that will be crucial in the development and delivery of future therapeutic regimes optimized for the individual patient. 10.1021/pr3001628
    Traditional Chinese medicine formulas for irritable bowel syndrome: from ancient wisdoms to scientific understandings. Xiao Hai-Tao,Zhong Linda,Tsang Siu-Wai,Lin Ze-Si,Bian Zhao-Xiang The American journal of Chinese medicine Traditional Chinese Medicine (TCM) serves as the most common alternative therapeutic approach for Western medicine and benefits IBS patients globally. Due to the lack of scientific evidence in the past, TCM formulas were not internationally well recognized as promising IBS remedies. In this review, firstly, we present the etiology and therapy of IBS in terms of traditional Chinese medical theory. Secondly, we summarize the clinical randomized controlled trials (RCTs) of TCM formulas for IBS patients that are available in the literature (from 1998 to September 2013), in which 14 RCTs conducted of high quality were discussed in detail. Of the 14 selected trials, 12 of those concluded that TCM formulas provided superior improvement in the global symptoms of IBS patients over the placebo or conventional medicines. As well, all 14 RCTs suggested that TCM formulas have good safety and tolerability. Last but not least, we explore the pharmacological mechanisms of the anti-IBS TCM formulas available in the literature (from 1994 to September, 2013). Collectively, in combating IBS symptoms, most TCM formulas exert multi-targeting actions including the regulation of neurotransmitters and hormones in the enteric nervous system (ENS), modulation of smooth muscle motility in the gastrointestinal (GI) tract, modulation of the hypothalamic-pituitary-adrenal (HPA) axis, attenuation of intestinal inflammation and restoration of intestinal flora, etc. In conclusion, TCM formulas appear to be promising for IBS treatment. This review provides a useful reference for the public in furthering a better understanding and acceptance of TCM formulas as IBS remedies. 10.1142/S0192415X15500019
    Comparative metabolism of the eight main bioactive ingredients of gegen qinlian decoction by the intestinal flora of diarrhoeal and healthy piglets. Liu Chang-Shun,Liang Xiao,Wei Xiao-Han,Chen Fei-Long,Tang Qing-Fa,Tan Xiao-Mei Biomedical chromatography : BMC Diarrhoeal diseases alter the composition of intestinal flora, thereby affecting the efficacy of herbal medicinal formulations. Gegen Qinlian decoction (GQD), a Chinese traditional herbal formulation, is widely used to treat infectious diarrhoea. However, little is known about the microbial disposition of GQD in the diarrhoeal state. In this study, the comparative metabolism of components of GQD by diarrhoeal and normal intestinal flora was investigated in vitro. UPLC-MS/MS was performed for simultaneous analysis of eight ingredients of GQD in bacterial solution. The type, activities, and sources of microbial enzymes were also investigated. Microbial metabolism of daidzin, genistin and liquiritin (metabolized by β-glucosidase); baicalin, wogonoside and glycyrrhizin (metabolized by β-glucuronidase); and berberine and coptisine (metabolized via nitroreductase) was faster in the diarrhoeal group than in the normal group. Moreover, the activities of these enzymes in the diarrhoeal group were higher than those in the normal group. This difference might be associated with the increase in Escherichia spp. Thus, a change in the metabolism of components by diarrhoeal intestinal flora is associated with a preponderance of Escherichia spp., which might improve the efficacy of GQD. These findings have implications for understanding the action mechanism of GQD for diarrhoea treatment in terms of the microbial milieu. 10.1002/bmc.4421
    [Application of active components from traditional Chinese medicine in treatment of inflammatory bowel disease]. Shao Mei-Juan,Yan Yu-Xi,Qi Qing,Tang Wei,Zuo Jian-Ping Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica Inflammatory bowel disease(IBD) is a non-specific and chronic recurrent autoimmune disease that involves the gastrointestinal tract. Clinical symptoms of intestinal bleeding, diarrhea, and weight loss threat to human health and induce colorectal cancer. The pathogenesis included living environment, genetic factors, immune cell infiltration and immune stress, weakened mucosal barrier defense and intestinal flora imbalance. At present, clinical treatment drugs mainly include aminosalicylic acid, corticosteroids, immunosuppressants, biological agents, etc., in view of the disadvantages of poor therapeutic effect and expensive price. The active ingredients of traditional Chinese medicine(TCM) in the treatment IBD have various biological activities and multiple targets such as anti-inflammatory, antibacterial, anti-tumor and immune regulation. This article summarized the application and the research progress in protecting intestinal epithelial barrier, maintaining intestinal microbial homeostasis, inhibiting causative factors, and regulating Th1/Th17/Treg balance about TCM in the treatment of IBD. The review provided new ideas for further development of the new drugs on the mechanism based on active ingredients of TCM in IBD treatment. 10.19540/j.cnki.cjcmm.20180907.001
    [Effects of Shengmai Jianghuang San on intestinal flora in nude mice with radio resistant cells of nasopharyngeal carcinoma]. Yang Jia-Bin,Zhu Dao-Qi,Shao Meng,Li Ai-Wu,Liu Zhao-Ru,Gao Rui-Jiao,Liu Shi-Ya,Lou Dan-Dan,Lyu Ying,Fan Qin Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica Modern pharmacological studies have shown that Shengmai San has the effects of enhancing immunity and improving blood circulation, and Curcumae Longae Rhizoma(Jianghuang) has anti-inflammatory, anti-cancer, anti-oxidation and other functions. Shengmai San combined with Jianghuang is a new research direction in the study of anti-tumor of traditional Chinese medicines. The main treatment for nasopharyngeal carcinoma is radiation therapy, but radiation therapy can cause a variety of side effects, and it also changes the composition of the intestinal flora. In this study, the 16 s rDNA sequencing platform was used to perform macro-sequence sequencing of the intestinal flora samples of nude mice bearing the veins of Shengmai Jianghuang San, and then the results of intestinal flora data were analyzed to investigate the effect of Shengmai Jianghuang San on tumors. The results showed that Shengmai Jianghuang San combined with irradiation could enhance the therapeutic effect of tumor treatment. Radiation therapy would reduce the total number and diversity of intestinal flora in nude mice, and also change the structure of the flora. Shengmai Jianghuang San could protect the diversity of colonies, and also partially restore the colony imbalance caused by irradiation. This study provides a research idea for Shengmai Jianghuang San as a sensitizing adjuvant for radiotherapy of nasopharyngeal carcinoma. 10.19540/j.cnki.cjcmm.20181203.001
    Regulation of Shaoyao Ruangan Mixture on Intestinal Flora in Mice With Primary Liver Cancer. Zhen Hongde,Qian Xiang,Fu Xiaoxuan,Chen Zhuo,Zhang Aiqin,Shi Lei Integrative cancer therapies BACKGROUND:Shaoyao Ruangan mixture (SRM) has been applied clinically for more than 20 years in Zhejiang Cancer Hospital to treat patients with primary liver cancer (PLC). Intestinal microecology plays an important role in the emergence of liver diseases. This study aimed to reveal connections among SRM, intestinal microbiota and PLC, and the potential targets of SRM for liver cancer. METHODS:We established a control group, a PLC model group, and a treatment group of mice to analyze the inhibitory effect of SRM on PLC and its intestinal flora target. We also evaluated drug efficacy of SRM and analyzed specific changes in intestinal flora by 16S rDNA sequencing of stools. As the serum interleukin (IL)-10 level could be an independent prognostic factor for unresectable liver cancer, we detected IL-10 levels and analyzed their association with the abundance of specific bacteria. RESULTS:Liver tumors in the treatment group were smaller and fewer than those in the model group ( P = .046). The abundance of Bacteroides was significantly higher in the model group than that in the control group, while SRM significantly reduced the increasing abundance of Bacteroides in mice with PLC. We found that the IL-10 level was positively correlated with the abundance of Bacteroides. CONCLUSION:SRM can effectively inhibit the progression of PLC and increase Bacteroides abundance. In view of the association between Bacteroides and liver cancer and the significant positive correlation between Bacteroides and IL-10 levels, Bacteroides may be the target intestinal flora of SRM to inhibit PLC. 10.1177/1534735419843178
    [Regulatory effect of traditional Chinese medicine on intestinal microbiota]. Yu Lan,Xing Zhi-Kai,Mi Shuang-Li,Wu Xia Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica As a large micro-ecosystem in the human body,the intestinal microbiota is closely associated with the occurrence of many diseases.The clinical investigations and animal experiments have showed that traditional Chinese medicine(TCM) could maintain the balance of the intestinal micro-ecological system.This review summarized the research methods and literatures on the regulation effects of TCM,including different effective ingredients,extracts and Chinese herbal formulae,on intestinal microflora in recent five years,in order to provide a reference for the further research and development of TCM. 10.19540/j.cnki.cjcmm.20181101.013
    [Interaction of effective ingredients from traditional Chinese medicines with intestinal microbiota]. Zu Xian-Peng,Lin Zhang,Xie Hai-Sheng,Yang Niao,Liu Xin-Ru,Zhang Wei-Dong Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica A large number and wide varieties of microorganisms colonize in the human gastrointestinal tract. They construct an intestinal microecological system in the intestinal environment. The intestinal symbiotic flora regulates a series of life actions, including digestion and absorption of nutrient, immune response, biological antagonism, and is closely associated with the occurrence and development of many diseases. Therefore, it is greatly essential for the host's health status to maintain the equilibrium of intestinal microecological environment. After effective compositions of traditional Chinese medicines are metabolized or biotransformed by human intestinal bacteria, their metabolites can be absorbed more easily, and can even decrease or increase toxicity and then exhibit significant different biological effects. Meanwhile, traditional Chinese medicines can also regulate the composition of the intestinal flora and protect the function of intestinal mucosal barrier to restore the homeostasis of intestinal microecology. The relevant literatures in recent 15 years about the interactive relationship between traditional Chinese medicines and gut microbiota have been collected in this review, in order to study the classification of gut microflora, the relationship between intestinal dysbacteriosis and diseases, the important roles of gut microflora in intestinal bacterial metabolism in effective ingredients of traditional Chinese medicines and bioactivities, as well as the modulation effects of Chinese medicine on intestinal dysbacteriosis. In addition, it also makes a future prospect for the research strategies to study the mechanism of action of traditional Chinese medicines based on multi-omics techniques. 10.4268/cjcmm20161002
    The Intervention Effect of Traditional Chinese Medicine on the Intestinal Flora and Its Metabolites in Glycolipid Metabolic Disorders. Di Sha,Wang Yitian,Han Lin,Bao Qi,Gao Zezheng,Wang Qing,Yang Yingying,Zhao Linhua,Tong Xiaolin Evidence-based complementary and alternative medicine : eCAM Metabolic syndrome (MS), which includes metabolic disorders such as protein disorder, glucose disorder, lipid disorder, and carbohydrate disorder, has been growing rapidly around the world. Glycolipid disorders are a main type of metabolic syndrome and are characterized by abdominal obesity and abnormal metabolic disorders of lipid, glucose, and carbohydrate utilization, which can cause cardiovascular and cerebrovascular diseases. Glycolipid disorders are closely related to intestinal flora and its metabolites. However, studies about the biological mechanisms of the intestinal flora and its metabolites with glycolipid disorders have not been clear. When glycolipid disorders are treated with drugs, a challenging problem is side effects. Traditional Chinese medicine (TCM) and dietary supplements have fewer side effects to treat it. Numerous basic and clinical studies have confirmed that TCM decoctions, Chinese medicine monomers, or compounds can treat glycolipid disorders and reduce the incidence of cardiovascular disease. In this study, we reviewed the relationship between the intestinal flora and its metabolites in glycolipid metabolic disorders and the effect of TCM in treating glycolipid metabolic disorders through the intestinal flora and its metabolites. This review provides new perspectives and strategies for future glycolipid disorders research and treatment. 10.1155/2019/2958920