Taraxasterol alleviates liver fibrosis by suppressing hepatic stellate cell activation via the HSD11B1-ERK MAPK signaling axis.

Authors

Peng Wang, Haoxiong Zhou, Yuming Ding, Yan Chen, Huiling Liu, Jie Jiang, Bin Wu

Published in

Acta biochimica et biophysica Sinica. Aug 03, 2026. Epub Aug 03, 2026.

Abstract

Taraxasterol (TAR) exerts therapeutic effects on various liver diseases via its inherent hepatoprotective and anti-inflammatory properties. However, the mechanism by which TAR treats hepatic fibrosis remains unclear. This study aims to identify the potential targets and specific molecular mechanisms underlying the therapeutic effects of TAR on hepatic fibrosis. DDC- and CCl ₄-induced mouse models of hepatic fibrosis are established. The human hepatic stellate cell (HSC) line LX-2 and primary mouse HSCs are used for in vitro experiments. Transcriptomics, network pharmacology, single-cell transcriptomics, and molecular docking are employed to identify potential therapeutic targets of TAR for hepatic fibrosis. Functional validation is performed via HSD11B1 overexpression and knockdown experiments, and the regulatory role of the ERK MAPK pathway is verified using the specific inhibitor U0126. Histological staining results show that TAR significantly alleviates DDC- and CCl ₄-induced hepatic fibrosis in mice and reduces associated liver injury. In vitro assays reveal that TAR effectively reverses TGF-β-induced activation of LX-2 cells and primary mouse HSCs. Multi-omics and docking analyses identify HSD11B1 as a direct target of TAR, whose downregulation in activated HSCs is restored by TAR treatment. Functional experiments demonstrate that overexpression of HSD11B1 attenuates TGF-β-induced HSC activation, while HSD11B1 knockdown abolishes the therapeutic effects of TAR. Subsequent transcriptomic analysis confirms that HSD11B1 suppresses the ERK MAPK pathway, and knockdown of HSD11B1 compromises the therapeutic efficacy of the ERK MAPK inhibitor U0126. In summary, TAR alleviates liver fibrosis by inhibiting HSC activation through the HSD11B1-ERK MAPK axis.

PMID:
42550670
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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