Cardioprotection effect of Yiqi–Huoxue–Jiangzhuo formula in a chronic kidney disease mouse model associated with gut microbiota modulation and NLRP3 inflammasome inhibition

• Published in: Biomedicine & pharmacotherapy Vol. 152; p. 113159
• Main Authors: Liu, Tongtong, Lu, Xiaoguang, Gao, Wenya, Zhai, Yuanyuan, Li, Han, Li, Shangheng, Yang, Liping, Ma, Fang, Zhan, Yongli, Mao, Huimin
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.08.2022; Elsevier
• Subjects: 5/6 nephrectomy; Cardioprotection; Gut microbiota; NLRP3 inflammasome; Trimethylamine N-oxide; Yiqi–Huoxue–Jiangzhuo formula; Gut microbiota; Yiqi–Huoxue–Jiangzhuo formula; Cardioprotection; 5/6 nephrectomy; Trimethylamine N-oxide; NLRP3 inflammasome
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113159

The pathogenesis and treatment of cardiovascular disease mediated by chronic kidney disease (CKD) are key research questions. Specifically, the mechanisms underlying the cardiorenal protective effect of Yiqi–Huoxue–Jiangzhuo formula (YHJF), a traditional Chinese herbal medicine, have not yet been clarified. A classical CKD mouse model was constructed by 5/6 nephrectomy (Nx) to study the effects of YHJF intervention on 5/6 Nx mice cardiorenal function, gut microbial composition, gut-derived metabolites, and NLRP3 inflammasome pathways. YHJF improved cardiac dysfunction and reversed left ventricular hypertrophy, myocardial hypertrophy, and interstitial fibrosis in 5/6 Nx mice. In addition, YHJF inhibited activation of the NLRP3 inflammasome and downregulated the expression of TNF-α and IL-1β both in the heart and serum; reconstitution of the intestinal flora imbalance was also found in 5/6 Nx mice treated with YHJF. Spearman’s correlation and redundancy analyses showed that changes in the intestinal flora of 5/6 Nx mice were related to clinical phenotype and serum inflammatory levels. Treatment with YHJF effectively protected the heart function of 5/6 Nx mice; this effect was attributed to inhibition of NLRP3 inflammasome activation and regulation of intestinal microbial composition and derived metabolites. YHJF has potential for improving intestinal flora imbalance and gut-derived toxin accumulation in patients with CKD, thereby preventing cardiovascular complications. [Display omitted] •Yiqi-Huoxue–Jiangzhuo formula (YHJF) is a traditional Chinese medicine with cardio-renal protective effects.•YHJF improves gut microbial structure and inhibits NLRP3 inflammasome activation in CKD mice of 5/6 nephrectomy (Nx).•There is a correlation between gut microbes and inflammatory response in 5/6 Nx mice.•The cardioprotective effect of YHJF is associated with NLRP3 inflammasome and gut microbes.