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The Role of the Gut Microbiota in Coronary Heart Disease. Liu Huagang,Zhuang Junli,Tang Peng,Li Jie,Xiong Xiaoxing,Deng Hongping Current atherosclerosis reports PURPOSE OF REVIEW:This review focuses on recent evidence examining the role gut microbiota play in coronary heart disease. It also provides a succinct overview of current and future therapies targeting the gut microbiota for coronary heart disease risk reduction. RECENT FINDINGS:A consensus has been reached that differences exist in the gut microbiotas of patients with coronary heart disease. Studies have shown that the gut microbiota is associated with obesity, diabetes, dyslipidemia, and hypertension, which are risk factors for coronary heart disease. The gut microbiota is involved in mediating basic metabolic processes, such as cholesterol metabolism, uric acid metabolism, oxidative stress, and inflammatory reactions, through its metabolites, which can induce the development of atherosclerosis and coronary heart disease. Interfering with the composition of gut microbiota, supplementing probiotics, and fecal donation are active areas of research to potentially prevent and treat coronary heart disease. Gut microbiota are causally associated with coronary heart disease. We analyzed the gut microbiota's effects on risk factors for coronary heart disease and studied the effects of gut microbiota metabolites on coronary heart disease. Gut microbiota is a potential target for preventing and treating coronary heart disease. 10.1007/s11883-020-00892-2
Changes of gut microbiome composition and metabolites associated with hypertensive heart failure rats. Li Lin,Zhong Sen-Jie,Hu Si-Yuan,Cheng Bin,Qiu Hong,Hu Zhi-Xi BMC microbiology BACKGROUND:The potential role of the gut microbiome (GM) in heart failure (HF) had recently been revealed. However, the underlying mechanisms of the GM and fecal metabolome in HF have not been characterized. The Dahl salt-sensitive rat model of hypertensive heart failure (H-HF) was used to study the clinical symptoms and characteristics. To elucidate the pathogenesis of HF, we combined 16S rRNA gene sequencing and metabolomics to analyze gut microbial compositions and fecal metabolomic profiles of rats with H-HF. RESULTS:PCoA of beta diversity shown that the gut microbiome composition profiles among the three groups were separated. Gut microbial composition was significantly altered in H-HF rats, the ratio of Firmicutes to Bacteroidetes(F/B) increased and the abundance of Muribaculaceae, Lachnospiraceae, and Lactobacillaceae decreased. Significantly altered levels of 17 genera and 35 metabolites were identified as the potential biomarker of H-HF. Correlation analysis revealed that specific altered genera were strongly correlated with changed fecal metabolites. The reduction in short-chain fatty acids (SCFA)-producing bacteria and trimethylamine N-oxide (TMAO) might be a notable characteristic for H-HF. CONCLUSIONS:This is the first study to characterize the fecal microbiome of hypertensive heart failure by integrating 16S rRNA gene sequencing and LC-MS-based metabolomics approaches. Collectively, the results suggesting changes of gut microbiome composition and metabolites are associated with hypertensive heart failure rats. 10.1186/s12866-021-02202-5
Application of Proteomics and Metabonomics to Reveal the Molecular Basis of Atractylodis Macrocephalae Rhizome for Ameliorating Hypothyroidism Instead of Hyperthyroidism. Chen Jing,Dou Peiyuan,Xiao Hang,Dou Deqiang,Han Xueying,Kuang Haixue Frontiers in pharmacology As the treatments of diseases with Chinese herbs are holistic and characterized by multiple components, pathways, and targets, elucidating the efficacy of Chinese herbs in treating diseases, and their molecular basis, requires a comprehensive, network-based approach. In this study, we used a network pharmacology strategy, as well as proteomics and metabonomics, to reveal the molecular basis by which rhizome (AMR) ameliorates hypothyroidism. Eighteen main compounds from AMR and its fractions (volatile oil fraction, crude polysaccharides fraction, lactones fraction, oligosaccharide fraction, and atractyloside fraction) were identified by HPLC, and their targets were screened using the TCMSP database and Swiss Target Prediction. Disease targets were gathered from the TTD, CTD and TCMSP databases. Hub targets were screened by different plug-ins, such as Bisogene, Merge, and CytoNCA, in Cytoscape 3.7.1 software and analyzed for pathways by the DAVID database. Hypothyroidism and hyperthyroidism pharmacological models were established through systems pharmacology based on proteomic and metabolomic techniques. Finally, AMR and its fractions were able to ameliorate the hypothyroidism model to different degrees, whereas no significant improvements were noted in the hyperthyroidism model. The lactones fraction and the crude polysaccharides fraction were considered the most important components of AMR for ameliorating hypothyroidism. These amelioration effects were achieved through promoting substance and energy metabolism. In sum, the integrative approach used in this study demonstrates how network pharmacology, proteomics, and metabolomics can be used effectively to elucidate the efficacy, molecular basis, and mechanism of action of medicines used in TCM. 10.3389/fphar.2021.664319
Studies on the compatibility mechanism and material basis of Danggui Buxue Decoction against anemia mice using metabonomics and network pharmacology. Liu YueTao,Ju Yanhong,Qin XueMei The Journal of pharmacy and pharmacology OBJECTIVES:To reveal the compatibility mechanism and material basis of Danggui Buxue decoction (DBD) against anaemia. METHODS:UHPLC-Q-Exactive-MS based serum metabonomics was applied to decipher the compatibility of DBD against anaemia mice. Meanwhile, network pharmacology was used to reveal the material basis of DBD based on the obtained differential metabolites. KEY FINDINGS:Metabonomic results indicated that 17 serum differential metabolites were closely related to anaemia. DBD, Huangqi (HQ) and Danggui (DG) could significantly ameliorate 13, 6 and 4 serum metabolites in anaemia mice, respectively. 17 serum differential metabolites were linked 140 corresponding targeted genes obtained by Metscape. In addition, 6649 targets genes related anaemia were obtained by network pharmacology. At last, six important targets genes were screened as hopeful targets for the treatment of anaemia through integrating them. Molecular docking further illustrated that eight active components of DBD including mairin, hederagenin, etc. played important roles in treating anaemia. CONCLUSIONS:DBD produced the best effect by compatibility with HQ and DG in treating anaemia. The approach provided the insights into the compatibility mechanism and material basis of TCM in treating anaemia coupling network pharmacology. 10.1093/jpp/rgab016
An Integrative Pharmacology-Based Strategy to Uncover the Mechanism of Xiong-Pi-Fang in Treating Coronary Heart Disease with Depression. Zhang Lihong,Zhang Yu,Zhu Mingdan,Pei Limin,Deng Fangjun,Chen JinHong,Zhang Shaoqiang,Cong Zidong,Du Wuxun,Xiao Xuefeng Frontiers in pharmacology This study aimed to explore the mechanism of Xiong-Pi-Fang (XPF) in the treatment of coronary heart disease (CHD) with depression by an integrative strategy combining serum pharmacochemistry, network pharmacology analysis, and experimental validation. An ultrahigh performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) method was constructed to identify compounds in rat serum after oral administration of XPF, and a component-target network was established using Cytoscape, between the targets of XPF ingredients and CHD with depression. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to deduce the mechanism of XPF in treating CHD with depression. Finally, in a chronic unpredictable mild stress (CUMS)-and isoproterenol (ISO)-induced rat model, TUNEL was used to detect the apoptosis index of the myocardium and hippocampus, ELISA and western blot were used to detect the predicted hub targets, namely AngII, 5-HT, cAMP, PKA, CREB, BDNF, Bcl-2, Bax, Cyt-c, and caspase-3. We identified 51 compounds in rat serum after oral administration of XPF, which mainly included phenolic acids, saponins, and flavonoids. Network pharmacology analysis revealed that XPF may regulate targets, such as , , , , , , , , , , cAMP signaling pathway, and cell apoptosis process in the treatment of CHD with depression. ELISA analysis showed that XPF decreased Ang-II content in the circulation and central nervous system, inhibited 5-HT levels in peripheral circulation, and increased 5-HT content in the central nervous system and cAMP content in the myocardia and hippocampus. Meanwhile, western blot analysis indicated that XPF could upregulate the expression levels of PKA, CREB, and BDNF both in the myocardia and hippocampus. TUNEL staining indicated that the apoptosis index of myocardial and hippocampal cells increased in CUMS-and ISO-induced CHD in rats under depression, and XPF could increase the expression of Bcl-2, inhibit the expression of Bax, Cyt-c, and caspase-3, and rectify the injury of the hippocampus and myocardium, which exerted antidepressant and antimyocardial ischemia effects. Our study proposed an integrated strategy, combining serum pharmacochemistry and network pharmacology to investigate the mechanisms of XPF in treating CHD with depression. The mechanism of XPF in treating CHD with depression may be related to the activation of the cAMP signaling pathway and the inhibition of the apoptosis. 10.3389/fphar.2021.590602
Study of the Mechanism of Action of Guanxin Shutong Capsules in the Treatment of Coronary Heart Disease Based on Metabolomics. Wang Dan,Shi Chang,Ge Zhen-Hua,Wei Yu-Xi,Liu Tian-Tian,Wang Yue,Zhou Xin-Feng,Yang Zi-Jun,Wang Wei-Ting,Zhang Yan-Wen,Zhu Xue-Hui,Zhang Jun,Li Ying,Gong Min,Wu Xiao-Hui,Duan Hong-Quan Frontiers in pharmacology : Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy. : A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis. : GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis. : GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD. 10.3389/fphar.2021.650438
Metabolomics study on the therapeutic effect of traditional Chinese medicine Xue-Fu-Zhu-Yu decoction in coronary heart disease based on LC-Q-TOF/MS and GC-MS analysis. Yi Min,Li Qiuxia,Zhao Yuhang,Nie Shanshan,Wu Ning,Wang Dongsheng Drug metabolism and pharmacokinetics The present study aims is to investigate the metabolic mechanism of Xue-Fu-Zhu-Yu decoction (XFZYD) in the treatment of blood-stasis syndrome in Coronary Heart Disease (CHD). To that end, 30 CHD patients with Blood-Stasis Syndrome (BSS) and 20 healthy subjects were enrolled. LC-Q-TOF/MS analysis determined that in comparison between CHD with BSS patients (Group A) and healthy subjects (Group C), 59 significantly differential metabolites in the positive mode and 18 significantly differential metabolites in the negative mode. The metabolite constituents in the plasma of 30 CHD with BSS patients before (group A) and after 30 days of treatment (Group B), and 20 healthy subjects (Group C) were analyzed using LC-Q-TOF/MS and GC-MS. Based on multivariate statistical analysis (PCA, PLS-DA and OPLS-DA), we determined 69 differential metabolites. The levels of hemorheology indexes were significantly down-regulated after treatment. Metabolic pathway attribution analysis showed that lipid metabolism, amino acid metabolism and bile acid metabolism pathways are involved. Our study identifies the metabolic networks of CHD and demonstrates the efficacy of this metabolomics approach to systematically study the therapeutic effect of XFZYC on CHD. 10.1016/j.dmpk.2019.07.004
Anti-inflammatory and antioxidative effects of Dan-Lou tablets in the treatment of coronary heart disease revealed by metabolomics integrated with molecular mechanism studies. Journal of ethnopharmacology ETHNOPHARMACOLOGICAL EVIDENCE:The Dan-Lou tablet (DLT), a well-known Chinese prescription, has definitive clinical efficacy in the treatment of precordial discomfort and pain caused by coronary heart disease (CHD). However, the pharmacological mechanism of DLT in the treatment of CHD has not been clearly elucidated and needs to be further explored. AIM OF THE STUDY:We aimed to identify relevant biological pathways by assessing changes in biomarkers in response to DLT intervention in CHD to reveal the potential biological mechanism of DLT treatment for CHD. MATERIALS AND METHODS:The major chemical components in DLT were qualitatively analyzed using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and a model of CHD in rats was subsequently established with a high-fat diet and left anterior coronary artery ligation (LADCA) followed by DLT intervention. Next, the metabolic profile of rat serum samples was analyzed using nontargeted metabolomics, wherein changes in the metabolites in serum samples before and after DLT administration were measured by PLS-DA, and two pathways of DLT treatment for CHD were predicted. Finally, predicted metabolomic pathways were verified by detecting and analyzing tissues from the rat model, revealing the mechanism of DLT in the treatment of CHD. RESULTS:Forty-five major chemical components were identified by the chemical characterization of DLT. In terms of metabolism, 17 biomarkers of CHD in rats were identified. Among these biomarkers, linoleic acid, γ-linolenic acid and lysophosphatidylcholines (LPCs) were found to play an important role in energy metabolism and glycerophospholipid metabolism. Protein analysis revealed that EGFR phosphorylation was inhibited in CHD rats after DLT treatment, which lowered the expression of TNF-α, IL-6 and MMP9, decreased the expression levels of ox-LDL and MDA, and increased the expression of SOD. CONCLUSION:The mechanism of DLT in the treatment of CHD involves inhibiting the expression of EGFR and the activation of the MAPK signaling pathway by regulating glycerophospholipid metabolism (LPCs) and energy metabolism (linoleic acid and γ-linolenic acid). Therefore, inflammation-related (TNF-α, IL-6, MMP9) and oxidative stress-related (ox-LDL, MDA, SOD) indicators are affected, leading to the regulation of the oxidative stress state and anti-inflammatory effects. 10.1016/j.jep.2019.111911
Metabolomics and its application in the treatment of coronary heart disease with traditional Chinese medicine. Wu Gao-Song,Li Hou-Kai,Zhang Wei-Dong Chinese journal of natural medicines Traditional Chinese Medicine (TCM) is the treasure of Chinese Nation and gained the gradual acceptance of the international community. However, the methods and theories of TCM understanding of diseases are lack of appropriate modern scientific characterization systems. Moreover, traditional risk factors cannot promote to detection and prevent those patients with coronary artery disease (CAD) who have not developed acute myocardial infarction (MI) in time. To sum up, there is still no objective systematic evaluation system for the therapeutic mechanism of TCM in the prevention and cure of cardiovascular disease. Thus, new ideas and technologies are needed. The development of omics technology, especially metabolomics, can be used to predict the level of metabolites in vivo and diagnose the physiological state of the body in time to guide the corresponding intervention. In particular, metabolomics is also a very powerful tool to promote the modernization of TCM and the development of TCM in personalized medicine. This article summarized the application of metabolomics in the early diagnosis, the discovery of biomarkers and the treatment of TCM in CAD. 10.1016/S1875-5364(19)30037-8