Tetramethylpyrazine ameliorates metabolic dysfunction-associated steatohepatitis by modulating gut microbiota dysbiosis and restoring intestinal barrier integrity.

Authors

Xiaoli He, Linzhang Zhang, Yadi Zhu, Wei Liu, Jiawen You, Wenxuan Chen, Xinyi Fu, Shiyu Yang, Yanting Shao, Yiren Hu, Yunhao Li, Min Zheng, Hongjie Yang, Guangbo Ge, Zheng Yao, Yanming He

Published in

British journal of pharmacology. Sep 10, 2026. Epub Sep 10, 2026.

Abstract

This study investigated the therapeutic effects and gut-liver axis-related mechanisms of tetramethylpyrazine (TMP) in metabolic dysfunction-associated steatohepatitis (MASH).
Male C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet for 6 weeks to establish MASH. TMP or pioglitazone was administered during the final 3 weeks. Hepatic injury, intestinal barrier integrity, gut microbiota, bile acids (BAs), short-chain fatty acids (SCFAs) and faecal metabolomics were assessed using histology, biochemical assays, RT-qPCR, western blotting, 16S rDNA sequencing and metabolomics. Faecal microbiota transplantation (FMT) and lipopolysaccharide (LPS)-stimulated Caco-2 cells were used to evaluate microbiota-dependent and direct intestinal protective effects of TMP.
TMP alleviated hepatic steatosis, inflammation and fibrosis in MCD-fed mice. TMP decreased hepatic macrophage infiltration and inflammatory cytokines, including TNF-α, IL-1β and IL-6. In the intestine, TMP restored epithelial structure, increased faecal sIgA, reduced serum LPS, D-lactate, zonulin and TNF-α and up-regulated Claudin-1, ZO-1 and Occludin. TMP improved gut microbial diversity, suppressed proinflammatory bacteria and enriched beneficial taxa. FMT from TMP-treated donors partially reproduced the hepatoprotective effects in recipient mice. TMP further restored BA and SCFA homeostasis, regulated the FXR/FGF15/CYP7A1 axis and remodelled faecal metabolic profiles associated with lipid peroxidation and inflammation. In Caco-2 cells, TMP attenuated LPS-induced IL-1β and IL-6 expression and restored Occludin expression.
TMP exerts protective effects against MCD diet-induced MASH by improving hepatic pathology and restoring gut-liver axis homeostasis, including intestinal barrier integrity, gut microbiota composition, BA and SCFA metabolism and faecal metabolic balance.

PMID:
42723361
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.

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