Qiliqiangxin Modulates the Gut Microbiota and NLRP3 Inflammasome to Protect Against Ventricular Remodeling in Heart Failure

Abstract

Aims: Pathological left ventricular (LV) remodeling induced by multiple causes often triggers fatal cardiac dysfunction, heart failure (HF), and even cardiac death. This study is aimed to investigate whether qiliqiangxin (QL) could improve LV remodeling and protect against HF via modulating gut microbiota and inhibiting nod-like receptor pyrin domain 3 (NLRP3) inflammasome activation.Methods: Rats were respectively treated with QL (100 mg/kg/day) or valsartan (1.6 mg/kg/day) by oral gavage after transverse aortic constriction or sham surgery for 13 weeks. Cardiac functions and myocardial fibrosis were assessed. In addition, gut microbial composition was assessed by 16S rDNA sequencing. Furthermore, rats’ hearts were harvested for histopathological and molecular analyses including immunohistochemistry, immunofluorescence, terminal-deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphated nick end labeling, and Western blot.Key findings: QL treatment preserved cardiac functions including LV ejection fractions and fractional shortening and markedly improved the LV remodeling. Moreover, HF was related to the gut microbial community reorganization like a reduction in Lactobacillus, while QL reversed it. Additionally, the protein expression levels like IL-1β, TNF-α, NF-κB, and NLRP3 were decreased in the QL treatment group compared to the model one.Conclusion: QL ameliorates ventricular remodeling to some extent in rats with HF by modulating the gut microbiota and NLRP3 inflammasome, which indicates the potential therapeutic effects of QL on those who suffer from HF.

Qiliqiangxin Capsule Modulates Calcium Transients and Calcium Sparks in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

“…A recent study investigated the protective effect of QLQX on doxorubicin-induced cardiotoxicity in a rat model [ 25 ]. Left ventricular remodeling is also alleviated by QLQX in rats with pressure overload-induced heart failure [ 26 ].…”

NLRP3 inflammasome and pyroptosis in cardiovascular diseases and exercise intervention

“…Additionally, activation of NLRP3 inflammasome has been observed in LPSstimulated cardiac fibroblasts and myofibroblasts, suggesting that its potential contribution to myocardial dysfunction through NLRP3 inflammasome or pyroptosis (Zhang et al, 2014;Boza et al, 2016). Although more research is needed to fully understand how the NLRP3 inflammasome or pyroptosis contributes to HF pathogenesis and progression; recent studies indicate that targeting this pathway could lead to new treatments for this debilitating condition (Lu et al, 2022;Xin et al, 2022).…”

Inflammatory Response: A Crucial Way for Gut Microbes to Regulate Cardiovascular Diseases

“…Nevertheless, a few studies have implicated an inflammation lowing effect by appropriately regulating gut microbiota, thus mitigating or reversing the ventricular remodeling [ 90 , 91 ]. At present, some traditional Chinese medicines, such as Qiliqiangxin (QL), were reported to stabilize the gut microbiota after heart failure, inhibiting myocardial fibrosis and cardiac remodeling by reducing the generation of inflammatory factors, such as NLRP3, IL-1B, and TNF-α [ 92 ].…”