Berberine ameliorates intestinal mucosal barrier dysfunction in nonalcoholic fatty liver disease (NAFLD) rats

Objective: To study the protective role of berberine (BBR) against nonalcoholic fatty liver disease (NAFLD) on intestinal barrier via investigating its effect on intestinal permeability and intestinal innate immune system in a rat model. Method: Sprague-Dawley rats were randomly divided into three groups: control rats (group N), high-fat diet (HFD) model rats (group M) and BBR-treated rats (group B). Rats in group M and group B were fed with HFD for 12 weeks to induce NAFLD. Rats in group B were then received 4 weeks of BBR administration with continuous HFD feeding. Samples were collected at 16th week. Results: HFD feeding increased the body weight of rats and caused liver steatosis as indicated by hematoxylin & eosin (H&E) staining. Analysis of serum parameters showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), endotoxin, interleukin-1 beta (IL-1 beta), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-alpha) were significantly higher in group M as compared group N. These results confirmed the successful establishment of NAFLD in rats. With 4 weeks of BBR administration, body weight of group B decreased significantly as compared with group M. Serum levels of ALT, AST, TC, TG, endotoxin, IL-1 beta, IL-18 and TNF-alpha reduced significantly and hepatocyte steatosis ameliorated. RT-PCR and Western blot analysis showed that BBR reduced the elevated mRNA and protein expressions of innate immune response elements NOD1, NOD2 and NLRP3 that were caused by HFD. BBR also antagonized the effect of NAFLD on Caspase-1 and Claudin-4 protein expressions. Conclusions: BBR alleviates endotoxemia, reduces serum lipids, increases liver function, reduces systemic inflammation and diminishes liver inflammation and steatosis in NAFLD rats. The protective effect of BBR against NALFD is achieved through ameliorating intestinal mucosal barrier dysfunction partly by improving permeability of intestinal mucosa and modulating intestinal innate immune components. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of King Saud University.