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The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.
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OBJECTIVE@#To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects.@*METHODS@#Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*RESULTS@#In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05).@*CONCLUSION@#BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.
Assuntos
Ratos , Animais , Ratos Sprague-Dawley , Microbioma Gastrointestinal , Cromatografia Líquida , Claudina-1 , Ocludina , RNA Ribossômico 16S , Espectrometria de Massas em Tandem , Medicamentos de Ervas Chinesas/farmacologia , Insuficiência CardíacaRESUMO
Objective: Trimethylamine oxide (TMAO) is a metabolite of intestinal flora and is known to promote the progression of atherosclerotic plaques. However, how TMAO works, including its effect on vascular endothelial cells, is not fully understood. This study aims to explore the biological role of TMAO in human umbilical vein endothelial cells (HUVECs) and the underlying mechanism. Methods: Cell pyroptosis and the loss of plasma membrane integrity were induced under TMAO stimulation in HUVECs. The plasma membrane integrity of the cells was measured by Hoechst 33342/propidium iodide (PI) staining and lactate dehydrogenase leakage assay, and the changes in cell morphology were observed by atomic force microscope. The expression of proteins related to pyroptosis was determined by Western blotting or immunofluorescence. Mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) activity in HUVECs was measured by the ALDH2 activity assay kit, and the level of reactive oxygen species (ROS) was detected by fluorescent probe DCFH-DA. Results: TMAO induced pyroptotic cell death, manifesting by the presence of propidium iodide-positive cells, the leakage of lactate dehydrogenase, the production of N-terminal gasdermin D (GSDMD-N), and the formation of plasma membrane pores. Moreover, TMAO induced elevated expression of inflammasome components, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3),apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-1 in cells. TMAO significantly inhibited ALDH2 activity and increased intracellular ROS production. However, the activation of ALDH2 by pharmacological manipulation attenuated TMAO-induced inflammasome activation and GSDMD-N production.Conclusion: TMAO induces pyroptosis of vascular endothelial cells through the ALDH2/ROS/NLRP3/GSDMD signaling pathway, which may be a potential therapeutic target for improving the treatment of atherosclerosis.
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AIM: To investigate the effect of water extract of Ziziphora clinopodioides Lam (WEZ) on improving atherosclerosis model rats. METHODS: Sixty SD rats were randomly selected and 50 rats of them were randomly selected for atherosclerosis model with high-fat emulsion and vitamin D3, and then randomly divided into atherosclerosis (AS) model group, low, medium, high WEZ group and the positive control group. After 8 weeks of drug intervention, the plasma of each group of rats was collected to detect total cholesterol (TC), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and trimethylamine oxide (TMAO) level. The correlation between plasma TMAO and TNF-α and IL-6 levels in AS rats was detected. The aortic tissue-embedded sections of rats in each group were taken out to compare the aortic plaque area/aortic lumen area (PA/LA) ratio. RESULTS: Compared with the blank control group, the serum TC and TG levels of the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the serum TC and TG levels of the middle and high dose WEZ group and the positive control group were significantly decreased, and the difference was statistically significant (P<0.05). Compared with the blank control group, the serum TNF-α and IL-6 levels in the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the serum TNF-α and IL-6 levels of the high-dose WEZ group and the positive control group were significantly decreased, and the difference was statistically significant (P<0.05). Compared with the blank control group, the plasma TMAO level of rats in the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the plasma TMAO levels of rats in the high-dose WEZ group and the positive control group decreased significantly, and the difference was statistically significant (P<0.05). The analysis of the correlation between TMAO level and TNF-α/IL-6 level showed that TMAO level was positively correlated with TNF-α level (P=0.001, r=0.673), and positively correlated with IL-6 level (P=0.002, r= 0.646). Compared with the blank control group, the PA/LA ratio of the AS model group increased significantly, and the difference was statistically significant (P<0.01). Compared with the AS model group, the PA/LA ratio of rats in the medium and high dose WEZ group and the positive control group decreased significantly, and the difference was statistically significant (P<0.05). CONCLUSION: WEZ may regulate TMAO levels, down-regulate TNF-α and IL-6 levels, and reduces TC and TG levels, thereby improving AS, but its mechanism still needs further study.
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AIM: To investigate the effect of telmisartan on intestinal flora and metabolite TMAO in atherosclerosis. METHODS: Seventeen ApoE