Quercetin, an ingredient of Jiedu Xiaozheng Yin, alleviates hepatocellular carcinoma progression by regulating CYP1A2/PTEN/PI3K/Akt axis.

Hepatocellular carcinoma (HCC) has a poor prognosis and limited treatment options. This study investigated the role and mechanism of Jiedu Xiaozheng Yin (JXY) in HCC using network pharmacology and in vivo/in vitro experiments. Active components of JXY and their potential therapeutic targets for HCC were identified via network pharmacology. A protein-protein interaction (PPI) network was constructed to identify core targets, and bioinformatics analysis confirmed their association with HCC. LC-MS/MS was used to isolate major components, which were then subjected to molecular docking with core targets. The effects of JXY on HCC were further validated through in vivo and in vitro experiments. Analysis of 171 core target genes was performed using PPI network screening and enrichment analysis. Quercetin was identified as the primary active component of JXY. Molecular docking confirmed its interaction with CYP1A2, which is overexpressed in HCC tissues. In vivo, JXY and quercetin significantly increased CYP1A2 and PTEN expression, while decreasing p-PI3K and p-Akt levels in HCC-bearing mice, thereby suppressing tumor growth and lung metastasis and promoting apoptosis. In vitro, both JXY and quercetin inhibited HCC cell proliferation and migration. CYP1A2 knockdown partially reversed, while its overexpression enhanced, these inhibitory effects. Quercetin, the main active component of JXY, upregulates CYP1A2 to promote PTEN expression, thereby inhibiting the PI3K/Akt signaling pathway and suppressing HCC progression.