Niu Yi-Jun, Xia Cheng-Jie, Ai Xin, Xu Wei-Ming, Lin Xiao-Tong, Zhu Ying-Qi, Zhu Hai-Yan, Zeng Xian, Cao Zhong-Lian, Zhou Wei, Huang Hai, Shi Xun-Long
Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai, 201203, China.
Department of Chemistry, Fudan University, Shanghai, 201203, China.
Acta Pharmacol Sin. 2025 Mar;46(3):653-661. doi: 10.1038/s41401-024-01408-3. Epub 2024 Oct 30.
Baicalin (BA), a natural component found in many traditional Chinese medicines, exerts protective effects against several viruses. Although our previous studies have revealed that the anti-hepatitis B virus (anti-HBV) activity of BA depends on hepatocyte nuclear factor (HNF) signaling, the specific mechanisms remain unclear. The present study explored the potential signaling mechanisms involved in BA-mediated HBV suppression. Transcriptomic analysis suggested that BA significantly modulates the estrogen receptor (ER) and AMPK signaling pathways in HepG2 cells. The ER alpha (ERα) binding affinity of BA and its estrogen-like agonist activity were subsequently verified through molecular docking assays, BA-ERα affinity detection experiments, ERα luciferase reporter gene assays, and qRT-PCR. ERα knockdown (shRNA) and AMPK inhibition (Compound C and doxorubicin [Dox]) experiments revealed that the sequential activation of the ERα-LKB1-AMPK-HNF signaling axis is essential for the anti-HBV effects of BA. This study indicates that BA may trigger the ERα-AMPKα-HNF pathway to inhibit HBV replication, providing insights into its potential protective mechanisms against other viruses.
黄芩苷（BA）是许多传统中药中的一种天然成分，对多种病毒具有保护作用。尽管我们之前的研究表明BA的抗乙型肝炎病毒（抗HBV）活性依赖于肝细胞核因子（HNF）信号传导，但其具体机制仍不清楚。本研究探讨了BA介导的HBV抑制所涉及的潜在信号传导机制。转录组分析表明，BA显著调节HepG2细胞中的雌激素受体（ER）和AMPK信号通路。随后通过分子对接试验、BA-ERα亲和力检测实验、ERα荧光素酶报告基因试验和qRT-PCR验证了BA与ERα的结合亲和力及其雌激素样激动剂活性。ERα敲低（shRNA）和AMPK抑制（化合物C和阿霉素[Dox]）实验表明，ERα-LKB1-AMPK-HNF信号轴的顺序激活对于BA的抗HBV作用至关重要。本研究表明，BA可能触发ERα-AMPKα-HNF途径来抑制HBV复制，为其对其他病毒的潜在保护机制提供了见解。
