Authors
Jiang-Tao Zhong, Hao Yue, Ze-Hao Wang, Ming Liu, Hai-Ming Sun, Jian Song
Published in
Phytotherapy research : PTR. Sep 29, 2026. Epub Sep 29, 2026.
Abstract
This study investigates the hepatoprotective effects and underlying molecular mechanisms of Oxypaeoniflorin (Opae) against alcohol-associated liver disease (ALD). An in vivo ALD mouse model was established by chronic feeding of Lieber-DeCarli EtOH-containing liquid diets combined with TEAD4 silencing is utilized to explore the protective function of Opae. Opae treatment effectively ameliorated alcoholic liver damage, accompanied by significant downregulation of hepatic P-YAP1, TEAD1, and TEAD4 levels, as well as reduced expression of the pyroptosis-associated proteins NLRP3 and IL-1β. RNA sequencing analysis further identified the NOD-like receptor/mitophagy/Hippo signaling axis as the core regulatory network mediating Opae-induced hepatoprotection. Mechanistically, dual-luciferase reporter assays in AML-12 hepatocytes validated the direct binding of TEAD4 to the NLRP3 promoter. Both siRNA-mediated TEAD4 silencing in AML-12 cells and shRNA-mediated hepatic TEAD4 silencing in mice markedly suppressed NLRP3 expression and alleviated liver inflammatory responses. Notably, TEAD4 depletion abrogated EtOH-induced NLRP3 activation, confirming the essential transcriptional regulatory role of TEAD4 on NLRP3. In addition to the intrinsic regulatory effect on hepatocytes, Opae inhibits pyroptosis in LPS-stimulated mouse peritoneal macrophages (MPMs). Conditioned medium collected from Opae-treated MPMs significantly attenuated EtOH-induced inflammatory injury in primary mouse hepatocytes. Collectively, Opae exerts prominent hepatoprotective effects in ALD by suppressing TEAD4-NLRP3-mediated pyroptosis.
PMID:
42810713
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.
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