Bazi Bushen maintains intestinal homeostasis through inhibiting TLR4/NFκB signaling pathway and regulating gut microbiota in SAMP6 mice

Abstract BACKGROUND Bazi Bushen is a Chinese patented medicine with multiple health benefits and geroprotective effects, yet, no research has explored its effects on intestinal homeostasis. In this study, we aimed to investigate the effect of Bazi Bushen on intestinal inflammation and the potential mechanism of gut microbiota dysbiosis and intestinal homeostasis in senescence‐accelerated mouse prone 6 (SAMP6). The hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to assess the function of the intestinal mucosal barrier. The enzyme‐linked immunosorbent assay (ELISA) and Western blotting were used to determine the level of intestinal inflammation. The aging‐related β‐galactosidase (SA‐β‐gal) staining and Western blotting were used to measure the extent of intestinal aging. The 16S ribosomal RNA (16S rRNA) was performed to analyze the change in gut microbiota composition and distribution. RESULTS Bazi Bushen exerted remarkable protective effects in SAMP6, showing a regulated mucosal barrier and increased barrier integrity. It also suppressed intestinal inflammation through down‐regulating pro‐inflammatory cytokines (IL‐6, IL‐1β, and TNF‐α) and inhibiting TLR4/NFκB signaling pathway (MYD88, p‐p65, and TLR4). Bazi Bushen improved intestinal aging by reducing the area of SA‐β‐gal‐positive cells and the expression of senescence markers p16, p21, and p53. In addition, Bazi Bushen effectively rebuilt the gut microbiota ecosystem by decreasing the abundance of Bacteroides and Klebsiella, whiles increasing the ratio of Lactobacillus/Bacteroides and the abundance of Akkermansia. CONCLUSION Our study shows that Bazi Bushen could serve as a potential therapy for maintaining intestinal homeostasis. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.