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Yangyin Runchang Decoction Improves Intestinal Motility in Mice with Atropine/Diphenoxylate-Induced Slow-Transit Constipation. Jiang Feng,Zhou Jin-Yong,Wu Jian,Tian Fang,Zhu Xuan-Xuan,Zhu Chang-Le,Yang Bo-Lin,Chen Yu-Gen Evidence-based complementary and alternative medicine : eCAM This study assessed the efficacy and mechanism of action of Yangyin Runchang decoction (YRD) in the treatment of slow-transit constipation (STC). ICR mice were randomly divided into four groups ( = 10/group) and treated with saline (normal control; NC), atropine/diphenoxylate (model control; MC; 20 mg/kg), or atropine/diphenoxylate plus low-dose YRD (L-YRD; 29.6 g/kg) or high-dose YRD (H-YRD; 59.2 g/kg). Intestinal motility was assessed by evaluating feces and the intestinal transit rate (ITR). The serum level of stem cell factor (SCF) and changes in interstitial cells of Cajal (ICCs) were also evaluated. Additionally, the expression of SCF and c-kit and the intracellular Ca concentration [Ca] were investigated. Fecal volume and ITR were greater in the L-YRD and H-YRD groups than in the MC group. The serum SCF level was lower in the MC group than in the NC group; this effect was ameliorated in the YRD-treated mice. Additionally, YRD-treated mice had more ICCs and elevated expression of c-kit and membrane-bound SCF, and YRD also increased [Ca] in isolated ICCs. YRD treatment in this STC mouse model was effective, possibly via the restoration of the SCF/c-kit pathway, increase in the ICC count, and enhancement of ICC function by increasing [Ca] . 10.1155/2017/4249016
Aqueous Extracts of Promoted Intestinal Motility in Loperamide-Induced Constipation Rats by Ameliorating the Interstitial Cells of Cajal. Yan Shuai,Yue Yin-Zi,Wang Xiao-Peng,Dong Hong-Li,Zhen Shu-Guang,Wu Ben-Sheng,Qian Hai-Hua Evidence-based complementary and alternative medicine : eCAM Traditional Chinese medicine was reported to have good effects in treating functional constipation. This work attempted to prove the effects of aqueous extracts of (AEHC) on STC treatment and to determine the possible mechanisms by a loperamide-induced slow transit constipation (STC) model. HPLC was performed for identification and confirmation of the bioactive components in the AEHC. It was found that AEHC attenuated STC responses based on increased fecal quantity, moisture content, and intestinal transit rate, as well as serum levels of GAS, MTL, SS, and CGRP. The protein and mRNA levels of c-kit, a labeling of interstitial cells of Cajal (ICC), also increased. Meanwhile, only the protein level of SCF, a ligand of c-kit, increased. The analysis of our data suggested that AEHC could obviously improve the function of ICC via a signaling pathway involving PI3K, SCF, and c-kit and enhance colonic motility indices such as GAS, MTL, SS, and CGRP. It is interesting to note that AEHC appeared to be effective on constipation, so further experiments are necessary to clarify the exact mechanisms involved. 10.1155/2017/6236904
[Mechanism of Aurantii Fructus Immaturus volatile oil in treatment of slow transit constipation based on network pharmacology]. Wang Liang-Feng,Liu Xiao-Li,Li Hui-Ting,Chen Qing-Yao,Wang Yao,Zou Bin,Yang Ming,Zhang Xiao-Fei,Wang Fang Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica To construct the active component-action target network diagram and protein-protein interaction(PPI) network diagram of Aurantii Fructus Immaturus volatile oil, so as to explore the mechanism of Aurantii Fructus Immaturus volatile oil in the treatment of slow transit constipation(STC) by analyzing the functions and pathways involved in the target. The chemical constituents of Aurantii Fructus Immaturus volatile oil were determined by gas chromatography-mass spectrometry(GC-MS). The targets of Aurantii Fructus Immaturus volatile oil were studied by PubChem, TCMSP, STITCH and Swiss Target Prediction. OMIM, Genecards-Search Resuits and TTD were used to screen out the targets of Slow Transit Constipation. The active component-action targets and PPI network diagram were constructed by Cytoscape 3.7.1. The target organ distribution was analyzed by BioGPS database. GO and KEGG pathways involved in the targets were analyzed by R language. The molecular docking between the components and the targets was verified by Discovery Studio 2.5 software. Finally, 15 volatile oil compounds from Aurantii Fructus Immaturus were detected, and 115 targets of volatile oil in the treatment of STC were predicted. GO enrichment analysis showed that the activity of Aurantii Fructus Immaturus volatile oil mainly involved blood circulation, circulation system process, response to steroid hormone, signal release and other biological processes. There were 23 KEGG enrichment pathways, among which Neuroactive ligand-receptor interaction, cAMP signaling pathway, Endocrine resistance, Calcium signaling pathway and Serotonergic synapse pathways played a significant role in STC. The results of molecular docking showed that relevant target proteins for the treatment of STC were ACHE, PTGS2, SLC6 A2 and CNR2.The multi-component, multi-target and multi-pathwaycharacteristics of Aurantii Fructus Immaturus volatile oil were revealed by network pharmacology, which provided a new therapeutic idea and method for the further study of the mechanism of Aurantii Fructus Immaturus volatile oil in the treatment of STC. 10.19540/j.cnki.cjcmm.20200207.302
Maren Pills Improve Constipation via Regulating AQP3 and NF-B Signaling Pathway in Slow Transit Constipation In Vitro and In Vivo. Evidence-based complementary and alternative medicine : eCAM BACKGROUND:Maren pills have been used to treat constipation. Aquaporin 3 (AQP3) plays a vital role in regulating water transfer in the colon. It has been reported that the downregulation of AQP3 can regulate liquid water metabolism and intestinal permeability in irritable bowel syndrome (IBS) rats' colon via NF-B pathway. In this study, we investigated whether the laxative effect of Maren pills is associated with the regulation of AQP3 and NF-B signaling pathway in the colon. METHODS:The compound diphenoxylate suspension-induced STC rats received Maren pills intragastrically for 1 consecutive week to evaluate the laxative effect of Maren pills involving the regulation of AQP3 and NF-B signaling pathway. Moreover, human intestinal epithelial cells (HT-29) were treated with drug serum to obtain in vitro data. RESULTS:Our results revealed that treatment with Maren pills increased the stool number, moisture content of feces, and intestinal transit rate in a dose-dependent manner. Maren pills significantly increased the AQP3, fibrosis transmembrane conductance regulator (CFTR), and protein kinase A (PKA) proteins in the colon of rats and in HT-29 cells. Mechanistically, Maren pills obviously inhibited the activation of NF-B pathway in the colon of rats and in HT-29 cells. CONCLUSION:These results suggest that the laxative effect of Maren pills is associated with the increased expression of AQP3 by downregulating NF-B signal pathway. 10.1155/2020/9837384
Metabolomics study on the therapeutic effect of the Chinese herb pair Fructus Aurantii Immaturus and Rhizoma Atractylodis Macrocephalae in constipated rats based on UPLC-Q/TOF-MS analysis. Yan Shuai,Hao Min,Yang Huiju,Sun Mingming,Wu Bensheng,Yue Yinzi,Wang Xiaopeng Annals of palliative medicine BACKGROUND:In China, Zhishi (Aurantii Fructus Immaturus) - Baizhu (Atractylodis Macrocephalae Rhizoma) is a well-known herb pair used to treat gastrointestinal motility disorders for thousands of years, and it has especially shown a definite advantage in the treatment of slow transit constipation (STC). However, the mechanism of Zhishi-Baizhu (ZSBZ) in the treatment of STC remains unclear. In this study, plasma metabolomics research combined with metabolic pathway analysis has been used to illuminate the potential mechanism of its effects against STC. METHODS:Parameters of intestinal transit ratio, plasma motilin (MTL), substance P (SP), adenosine triphosphate (ATP), histological alteration of the colon and MLCK expression in the colon were detected to evaluate the effects with respect to STC. Principal component analysis (PCA) was used to investigate the global metabolite alterations, while orthogonal partial least squares discriminant analysis (OPLS-DA) and t-test were used to filter potential metabolite markers. Moreover, metabolic pathway analysis was employed. RESULTS:Oral administration of ZSBZ significantly prevented the development of STC. It increased the expression of MTL and SP in serum, as well as the expression of ATP and MLCK in the colon. ZSBZ administration alleviated symptoms in loperamide-induced constipated rats, evidenced by the increase of intestinal transit ratio. Futhermore, 9 potential biomarkers of STC were screened, and the levels were all reversed to different degrees after ZSBZ administration. Metabolic pathway analysis showed that the improvement of STC by ZSBZ was mainly related to caffeine and vitamin B6 metabolism. CONCLUSIONS:Our study identifies the metabolic networks of constipated rats and demonstrates the efficacy of this metabolomics approach to systematically study the therapeutic effects of ZSBZ on constipation. 10.21037/apm-20-280
Curative Effect and Mechanism of Guiren Runchang Granules on Morphine-Induced Slow Transit Constipation in Mice. Sun Yihan,Yan Chengqiu,Jin Shifeng,Shi Chong,Zhao Jingming,Li Guofeng Evidence-based complementary and alternative medicine : eCAM Recent studies have identified the curative effects of traditional Chinese medicine for constipation. The mechanism of action of Guiren Runchang granules (GRGs) in the treatment of slow transit constipation (STC) was evaluated in this study. Here, we assessed the efficacy of GRG by comparing the differences in fecal characteristics, stool weight, and intestinal transit rate (ITR) among 6 groups ( = 12/group), which were administered three concentrations of GRG, mosapride, and saline. The influence of GRG on the SCF/c-kit pathway, AQP4, and serum motilin of mice was assessed through ELISA, western blot, and immunohistochemical analysis. The dry weight of mouse feces at 24 hr and ITR in the MD (medium-dose GRG; 9.44 g/kg/d) and HD (high-dose GRG; 18.88 g/kg/d) groups was higher than that in the MC (model control) group. The serum motilin of morphine-induced mice level was lower in the MC group than in the NC (normal control) group, and this condition was improved in the HD group. The HD group expressed significantly higher levels of SCF and c-kit protein but lower levels of AQP4 and simultaneously presented more SCF-positive and c-kit-positive cells. However, no differences in the serum SCF level were found among the six groups. Certain concentrations of GRG are effective in STC mice, the potential mechanism of which may be associated with repairing the SCF/c-kit pathway and reducing the expression of AQP4 in the colon. GRG improved the serum motilin level but had no influence on the serum SCF level. 10.1155/2020/5493192
The different effects of Chinese Herb Solid Drink and lactulose on gut microbiota in rats with slow transit constipation induced by compound diphenoxylate. Deng Zhitong,Fu Zhuotao,Yan Wen,Nie Kechao,Ding Lingli,Ma Duanhua,Huang Haodong,Li Tao,Xie Jianxing,Fu Linchun Food research international (Ottawa, Ont.) Slow transit constipation (STC) has become an epidemic medical problem. There are several kinds of drugs for constipation; however, each drug has its limitations. The gut microbiota has a close relationship with STC. Lactulose is an effective drug for constipation because it is a kind of bulking laxative and microbioecologic, and it relieves the syndromes of STC. We found that the Chinese Herb Solid Drink (CHSD), which contains medicine food homologous materials such as psyllium husk, sweetalmond, semen sesami nigrum, and hemp seed, has a similar effect on relieving constipation as lactulose, although it has different effects on the gut microbiota. We investigated the mechanisms of CHSD in rats with STC, induced by diphenoxylate, via constipation index and enzyme linked immunosorbent assay (ELISA) analyses using serum and 16S rDNA amplicon and gas chromatography-mass spectroscopy (GC-MS). CHSD enhanced the relative abundance of some types of gut microbiota, such as Blautia, Ruminococcus, Roseburia, Coprococcus, Lachnospira, and Phascolarctobacterium, while lactulose enhanced the relative abundance of Blautia, Phascolarctobacterium, Eubacterium, and Akkernansia in diphenoxylate-induced STC rats. Both CHSD and lactulose enhanced the level of short-chain fatty acids in the faeces of rats; however, the composition of those were different between the two drugs. From the perspective of the gut neuroendocrine system, both CHSD and lactulose could elevate neurotransmitters, such as motilin (MTL) and substance P (SP), which promote intestinal peristalsis and reduce the expression of vasoactive intestinal peptide, which inhibits intestinal peristalsis in the serum of STC rats. CHSD could elevate gastrin expression, which also promoted intestinal peristalsis in serum, while lactulose did not have this effect. Our findings suggest that CHSD may be an effective and safe therapeutic choice for STC. 10.1016/j.foodres.2021.110273
Paeoniflorin Improved Constipation in the Loperamide-Induced Rat Model via TGR5/TRPA1 Signaling-Mediated 5-Hydroxytryptamine Secretion. Zhan Yu,Wen Yong,Zhang Liang-Liang,Shen Xu-Long,Chen Xiao-Hui,Wu Xiao-Hai,Tang Xue-Gui Evidence-based complementary and alternative medicine : eCAM Slow transit constipation (STC) is a common type of constipation with a high incidence rate and a large number of patients. We aimed to investigate the therapeutic effects and potential mechanism of paeoniflorin (PAE) on loperamide-induced Sprague Dawley (SD) rat constipation models. Rats with loperamide-induced constipation were orally administered different concentrations of PAE (10, 20, or 40 mg/kg). In vitro, enterochromaffin (EC)-like RIN-14B cells were treated with 20, 40, or 80 g/ml PAE. We found that PAE treatment significantly improved the symptoms of constipation and increased the intestinal transit rate. Hematoxylin and eosin (H&E) staining showed that PAE alleviated colonic tissue pathological damage. Besides, our results implied that PAE concentration-dependently promoted the content of 5-hydroxytryptamine (5-HT) catalyzed by tryptophan hydroxylase (Tph)-1 in the serum of loperamide-induced rats and in RIN-14B cells. Western blot and immunofluorescence (IF) stain indicated that PAE also promoted the expression of G protein-coupled BA receptor 1 (TGR5), transient receptor potential ankyrin 1 (TRPA1), phospholipase C (PLC)-1, and phosphatidylinositol 4,5-bisphosphate (PIP2) and . RIN-14B cells were cotreated with a TGR5 inhibitor (SBI-115) to explore the mechanism of PAE in regulating the 5-HT secretion. We observed inhibition of TGR5 reversed the increase of 5-HT secretion induced by PAE in RIN-14B cells. We provided evidence that PAE could promote 5-HT release from EC cells and improve constipation by activating the TRPA1 channel and PLC-1/PIP2 signaling. Thus, PAE may provide therapeutic effects for patients with STC. 10.1155/2021/6076293
Transdermal Administration of Volatile Oil from - Alleviates Constipation in Rats by Altering Host Metabolome and Intestinal Microbiota Composition. Oxidative medicine and cellular longevity BACKGROUND:The - (ZhiShi, ZS-) (BaiZhu, BZ) pairs are often found in herbal formulas for constipation. The volatile oils of ZS and BZ (ZBVO) have good pharmacological activity against constipation, but the mechanism for treatment of slow transit constipation (STC) remains unclear. METHOD:A rat model using diphenoxylate tablets was constructed to investigate if transdermal administration of ZBVO would mediate intestinal microorganisms and fecal metabolites and improve STC symptoms. The regulatory effects of ZBVO at 0.15, 0.30, and 0.60 mL kg d on STC rats were assessed by measuring fecal water content, intestinal propulsion rate, histopathology, expression of gastrointestinal hormones, brain and intestinal peptides, and inflammatory factors. The changes in intestinal flora of STC rats were analyzed by 16S rRNA gene sequencing. Moreover, the untargeted fecal metabolomics analysis was performed by ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometer (UPLC-Q-TOF-MS) technology. RESULTS:The results showed that ZBVO had a modulating effect on STC by increasing the fecal water content and intestinal propulsion rate. Transdermal administration of ZBVO decreased serum levels of interleukin 6 (IL-6) and tumor necrosis factor- (TNF-) and increased the levels of gastrin (GAS) and substance P (SP). In addition, ZBVO increased 5-hydroxytryptamine (5-HT) levels and decreased vasoactive intestinal peptide (VIP) levels in colon and hippocampus tissues. The results of intestinal microbiota showed that ZBVO improved the diversity and abundance of intestinal microbiota and changed the community composition by decreasing and increasing , , and . And the feces metabolomics found that nicotinate and nicotinamide metabolism, purine metabolism, citrate cycle (TCA cycle), pyruvate metabolism, arachidonic acid metabolism, pyrimidine metabolism, and primary bile acid biosynthesis were modulated. CONCLUSION:These findings suggest that ZBVO can alleviate STC symptoms by promoting intestinal peristalsis, increasing fecal water content, regulating gastrointestinal hormone level, reducing the inflammatory response, and regulating brain and intestinal peptides after transdermal administration. And structural changes in the intestinal microbiota are closely related to host metabolism and intestinal microbiota destroyed in STC modeling could be significantly improved by the ZBVO, which provides a reference for the development of aromatic drug macrohealth products. 10.1155/2022/9965334
Research progress in the treatment of slow transit constipation by traditional Chinese medicine. Wang LiangFeng,Wu Fei,Hong YanLong,Shen Lan,Zhao LiJie,Lin Xiao Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Slow transit constipation (STC) is a common gastrointestinal disorder seriously impacting patients' quality of life. At present, although conventional chemical drugs effectively control STC symptoms in the short term, the long-term effects are poor, and the side effects are significant. In this regard, traditional Chinese medicine (TCM) offers an opportunity for STC treatment. Many pharmacological and clinical studies have confirmed this efficacy of TCM with multiple targets and mechanisms. AIM OF THE STUDY:This review attempted to summarize the characteristics of TCM (compound prescriptions, single Chinese herbs, and active ingredients) for STC treatment and discussed their efficacy based on analyzing the pathogenesis of STC. MATERIALS AND METHODS:The information was acquired from different databases, including PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases. We then focused on the recent research progress in STC treatment by TCM. Finally, the future challenges and trends are proposed. RESULTS:TCM has good clinical efficacy in the treatment of STC with multi-mechanisms. Based on the theory of syndrome differentiation, five kinds of dialectical treatment for STC by compound TCM prescriptions were introduced, namely: Nourishing Yin and moistening the intestines; Promoting blood circulation and removing blood stasis; Warming Yang and benefiting Qi; Soothing the liver and regulating Qi; and Benefiting Qi and strengthening the spleen. In addition, six single Chinese herbs and eight active ingredients also show good efficacy in STC treatment. CONCLUSIONS:TCM, especially compound prescriptions, has bright prospects in treating STC attributed to its various holistic effects. 10.1016/j.jep.2022.115075
Effects of Maren Pills on the Intestinal Microflora and Short-Chain Fatty Acid Profile in Drug-Induced Slow Transit Constipation Model Rats. Frontiers in pharmacology Slow transit constipation (STC) is becoming a common and frequently occurring disease in today's society, and it is necessary to explore the safe and effective treatment of STC. Our study aimed to investigate whether the laxative effect of Maren pills (MRW) is associated with the regulation of intestinal microflora and intestinal metabolism in the colon. Loperamide hydrochloride-induced STC rats received MRW intragastrically for two consecutive weeks to evaluate the laxative effect of MRW involving the regulation of intestinal microflora, intestinal metabolism, and 5-HT signaling pathway. Intestinal microflora was detected by 16s rDNA sequencing, intestinal metabolism of short-chain fatty acids (SCFAs) was detected by HPLC, and the 5-HT signaling pathway was detected by WB, ELISA, immunofluorescence, and immunohistochemical analysis. Our results revealed that the treatments with MRW increased not only the body weight, 24-h fecal number, 24-h wet fecal weight, 24-h dry fecal weight, fecal water content, and the intestinal propulsion rate but also the colonic goblet cell number, colonic Muc-2 protein expression, and colonic mucus layer thickness in the STC model rats. Moreover, MRW activated the 5-HT pathway by increasing the levels of 5-HT, 5-HIAA, 5-HT4R, CFTR, cAMP, and PKA in the colon tissue of STC rats. The 16S rDNA sequencing results showed that MRW improved the colonic microflora structure in colonic contents of STC rats, mainly by increasing and decreasing . Finally, we found that MRW regulated the SCFA metabolism in the colonic contents of the STC rats, mainly by increasing the contents of acetic acid, propionic acid, and butyric acid; the relative abundance of was positively correlated with either contents of acetic acid, propionic acid, and butyric acid, and the relative abundance of was negatively correlated. Our study further showed that MRW could improve constipation in STC rats, and the mechanism may be by regulating the intestinal microflora structure and improving the metabolism of SCFAs. 10.3389/fphar.2022.804723