Qige Huxin Formula Attenuates Isoprenaline-Induced Cardiac Fibrosis in Mice via Modulating Gut Microbiota and Protecting Intestinal Integrity

Background. The composition and metabolic activities of gut microbiota are strongly interconnected with cardiac fibrosis (CF) and heart failure (HF). Qige Huxin formula (QHF), a traditional Chinese medicine (TCM) formulation originating from a classical Fangji Huangqi decoction, has been widely used to clinically treat HF for decades. However, it is still unclear whether QHF alleviates CF by modulating gut microbiota and intestinal integrity. Purpose. This study aimed to investigate the cardioprotective effects of QHF in isoprenaline-induced CF through modulating gut microbiota and intestinal integrity. Methods. Fifty mice were randomly divided into five groups after one week of acclimatization feeding: control group, model group, 2.56 g/kg/ d group (low-dose QHF), 5.12 g/kg/d group (high-dose QHF), and meto group (15 mg/kg/d). The CF model was established by subcutaneously injecting the mice with isoprenaline (10 mg/kg/d for 14 days), followed by QHF treatment. The heart volume, cardiac weight index (CWI), serum myocardial enzymes, serum inflammatory cytokines, serum lipopolysaccharide, histopathology of the heart and colon tissues, ZO-1, and occludin of colon tissues were then measured. Fecal samples from mice were analyzed using 16S rRNA sequencing. Results. QHF treatment significantly reduced heart volume, CWI, and serum CK and CK-MB levels, attenuated cardiac histopathological alterations, and alleviated CF. QHF treatment also downregulated TNF-alpha, IL-1 beta, and IL-6 in serum. Moreover, QHF treatment decreased the serum level of lipopolysaccharide and maintained intestinal integrity by upregulating ZO-1 and occludin. The 16S rRNA microbiota analysis revealed that QHF treatment increased the relative abundance of Marvinbryantia and Phascolarctobacterium. Conclusions. QHF treatment exerts cardioprotective effects through modulating gut microbiota, protecting intestinal integrity, and alleviating inflammation. This study shows that gut microbiota may enhance heart-gut interaction.