Oroxyloside inhibits liver fibrosis and hepatocarcinogenesis dependent on hepatocyte-specific knockout of Atg5

作者：Yunyao Liu, Liu Chen, Xingyu Liu, Ran Tao, Ran Dong, Xiaosheng Wang, Xiaosheng Wang, Jiangti Luo, Hanhan Li, Yufen Zheng, Lei Qiang, Zhenzhong Deng, Xiaoping Wang, Xiaoping Wang · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.157053 · 被引用次数：4 · 研究领域：Flavonoids in Medical Research、Autophagy in Disease and Therapy、Berberine and alkaloids research

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality, is closely linked to liver fibrosis, yet effective preventive therapies remain elusive. Autophagy is a critical cellular process that maintains hepatic homeostasis, and its disruption is implicated in the progression of fibrosis and HCC. This study aimed to evaluate the efficacy of oroxyloside (OAG), a flavonoid derived from Scutellaria baicalensis, in preventing liver fibrosis associated with cancer. METHODS: ) and In vitro models with silenced Atg5 or PPARγ were used to investigate autophagy's role in OAG's therapeutic effects. To analyze the correlation between autophagy and hepatic fibrosis or cancer we use the TCGA and GSE database. Patient tissue samples (79 pairs) associated HCC was investigated by immunohistochemistry. RESULTS: This study demonstrates that OAG restores autophagic flux through the AMPK-ULK1 pathway in a PPARγ-dependent manner, reducing oxidative stress, DNA damage, and inflammatory cytokine IL-6 production. These mechanisms culminate in the inhibiting the activation of hepatic stellate cell activation and fibrosis progression. OAG also significantly attenuated liver tumor burden and improved survival in a chronic liver injury model. Importantly, the therapeutic effects of OAG were diminished in Atg5-deficient hepatocytes, highlighting its reliance on autophagy. This mechanistic insight differentiates OAG from existing anti-fibrotic or HCC therapies by target...