Xiao-Qing-Long Tang Prevents Cardiomyocyte Hypertrophy, Fibrosis, and the Development of Heart Failure with Preserved Ejection Faction in Rats by Modulating the Composition of the Gut Microbiota

Abstract

Background. Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect. Methods. The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota. Results. Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF. Conclusions. These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.

Potential Mechanism of Guizhi Decoction in Hypertension Treatment Based on Network Pharmacology and Dahl Salt-Sensitive Rat Model

“…These results were in line with earlier reports that showed that the improvement of cardiac in ammation and brosis was associated with decrease in blood pressure. [10,38] Based on the results of the network analysis and molecular docking, several targets such as AKT1, VEGFA, eNOS, ICAM-1, PTGS2, and ALB could be associated with the potential effect of GZD on hypertension. For example, AKT1 directly participates in the phosphorylation of eNOS at serine 1177, which could increase enzyme activity, NO production, and angiogenesis.…”

Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model

“…To further confirm the effects of GZD on cardiac fibrosis, immunohistochemical staining was performed to evaluate the expression levels of collagens I and III in the left ventricle. Collagens I and III are two important molecular mediators of collagen deposition and extracellular matrix (ECM) alterations during the pathological fibrotic process [ 24 ]. Furthermore, Collagens I and III also play a relatively important role in the PPI network.…”

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“…Evidence-Based Complementary and Alternative Medicine cardiomyocyte hypertrophy and fibrosis, and it could improve the intestinal mucosal histology by regulating the composition of gut microbiota [51]. Tong-Xie-Yao-Fang can effectively improve the intestinal permeability and enhance the intestinal mucosal barrier function [52].…”