Xinshuaifang improves oxidative stress injury and myocardial remodeling in acute heart failure: Association with the gut-heart axis

Abstract: Background: Acute heart failure (AHF) is a leading cause of death from cardiovascular disease and effective treatments are lacking. Objectives: To investigate whether Xinshuaifang improves oxidative stress injury and myocardial remodeling in AHF mice by regulating the gut-heart axis. Methods: C57BL/6 mice aged 8–10 weeks and weighing 20-25 g were randomized into 7 groups (n=8/group): control, AHF model, AHF+Xinshuaifang, AHF+control FMT, AHF+intervention FMT, AHF+Xinshuaifang+antibiotics and antibiotics-only control. AHF was induced by isoproterenol injection (5 mg/kg, 7 days). Gut microbiota composition, oxidative stress markers (MDA, GSH, SOD, MPO), cardiac function (LVDd, LVDs, LVEF, NT-proBNP), myocardial fibrosis and tight junction protein expression (ZO-1, Occludin, Claudin-1, Zonulin) were assessed. Results: Compared with controls, model mice showed significantly reduced Verrucomicrobia and Akkermansia abundance (P<0.01), increased MDA and GSH levels, decreased SOD activity and MPO levels, reduced LVEF, elevated NT-proBNP (P<0.01), decreased ZO-1, Occludin and Claudin-1 expression and increased Zonulin expression. Xinshuaifang intervention significantly reversed all these changes (P<0.01): it increased beneficial bacteria, reduced oxidative stress, improved cardiac function, upregulated ZO-1/Occludin/Claudin-1 and downregulated Zonulin. The FMT intervention group showed similar protective effects, whereas the Xinshuaifang+antibiotics group showed attenuated protection. Conclusion: Xinshuaifang improves cardiac function and alleviates oxidative stress and fibrosis in AHF mice by regulating gut microbiota, upregulating tight junction proteins and restoring intestinal barrier function.