Shugan Jiangzhuo Tablets mitigate non-alcoholic fatty liver disease by modulating TLR4/MyD88/NF-κB signaling pathway...

Shugan Jiangzhuo Tablets (SGJZ), a hospital-prepared traditional Chinese medicine formulation with extensive clinical application for over two decades, has demonstrated notable efficacy in Non-alcoholic fatty liver disease (NAFLD) management. Nevertheless, exact action process and therapeutic objectives of SGJZ remain to be fully elucidated.

This study aims to clarify how SGJZ alleviates lipid accumulation and inflammation in a NAFLD zebrafish.

A NAFLD zebrafish model was established by administering egg yolk powder diet for 21 consecutive days. Additionally, a pseudo-germ-free zebrafish model, induced using an antibiotic cocktail, was employed to delineate contribution of gut microbiota and intestinal barrier integrity to anti-NAFLD effects of SGJZ. Gut microbiota alterations were analyzed via 16S rRNA sequencing, providing further perspectives into influence of gut microbiota in NAFLD zebrafish model.

The results demonstrated that SGJZ significantly improved body weight, adiposity, lipid metabolism, pathological conditions, blood lipid profiles, and transaminase levels in NAFLD zebrafish. Additionally, SGJZ inhibited transcriptional activity of TLR4/MyD88/NF-κB pathway in liver, protected intestinal mucosal barrier, reduced lipopolysaccharide infiltration into liver, and favored abundance of beneficial microbiota. Notably, therapeutic effects of SGJZ were attenuated to varying degrees following antibiotic cocktail treatment, highlighting involvement of gut microbiota in its action.

Our findings highlight that SGJZ offers protection against NAFLD in zebrafish by influencing gut microbiota, where Cetobacterium emerges as a potential key microorganism, and suppressing liver inflammation via TLR4/MyD88/NF-κB signaling axis. All things considered, SGJZ is shaping up to be a promising candidate for keeping NAFLD in check.