Tetrastigma hemsleyanum Diels & Gilg ameliorates alcohol-associated liver disease by modulating the gut-liver axis and ferroptosis.

Authors

Lianghui Zhan, Qian Liu, Xuechun Jiang, Yijuan Hu, Jie Zhou, Sheng Zhu, Weiqing Liang, Jinbao Pu

Published in

Phytomedicine : international journal of phytotherapy and phytopharmacology. Volume 160. Pages 158614. Jul 20, 2026. Epub Jul 20, 2026.

Abstract

Alcohol-associated liver disease (ALD) encompasses a spectrum of hepatic injuries driven by chronic inflammation and oxidative stress. Tetrastigma hemsleyanum Diels & Gilg rootlets principle (THRP) displays hepatoprotective potential. However, its systematic mechanisms along the gut-liver axis are not yet fully elucidated.
To investigate the protective effects of THRP on ALD and elucidate its systemic regulation of microbial metabolites and hepatocyte fate.
Mice were pretreated with THRP for 7 days, followed by a 7-day co-administration of THRP and 40% ethanol. Liver injury, intestinal barrier integrity, and iron homeostasis were evaluated. The underlying mechanisms were explored using 16S rRNA and scRNA-seq.
THRP partially alleviated alcohol-induced hepatic steatosis, inflammatory cell infiltration, and elevated liver enzyme levels. In the gut, THRP restored mucosal barrier integrity and suppressed the expansion of the pathobiont s_Cryptobacteroides, which was associated with increased polyamine biosynthesis and reduced systemic lipopolysaccharide translocation. Further, scRNA-seq and pseudotime analyses suggested that ferroptosis-related pathways were altered in alcohol-stressed hepatocytes and associated with THRP intervention. THRP treatment was associated with a favorable shift in this ferroptotic trajectory, concomitant with the upregulation of the NRf2-GPX4 axis and potential modulation of the fibroblast-to-hepatocyte bone morphogenetic protein (BMP) signaling crosstalk. THRP treatment was also associated with altered fibroblast-to-hepatocyte BMP signaling patterns and reduced hepatic iron accumulation.
THRP protects against ALD by regulating gut-liver axis homeostasis and inhibiting hepatic ferroptosis, including suppression of pathobionts. These findings support THRP as a natural candidate for further preclinical and clinical studies on ALD.

PMID:
42555989
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.

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