复旦大学史训龙等研究人员合作发现，黄酮类化合物黄芩苷通过顺序激活ERα-AMPKα信号通路，下调病毒HNF依赖性HBV复制。这一研究成果于2024年10月30日在线发表在国际学术期刊《中国药理学报》上。

研究人员表示，黄芩苷（BA）是许多传统中药中的天然成分，对多种病毒具有保护作用。尽管研究人员之前的发现揭示了BA的抗乙型肝炎病毒（anti-HBV）活性依赖于肝细胞核因子（HNF）信号通路，但具体机制仍不清楚。

研究人员探讨了BA介导的HBV抑制可能涉及的信号机制。转录组分析表明，BA显著调节了HepG2细胞中的雌激素受体（ER）和AMPK信号通路。

研究通过分子对接实验、BA-ERα亲和力检测实验、ERα荧光素酶报告基因实验和qRT-PCR，验证了BA与ERα的结合亲和力及其类雌激素激动活性。ERα敲低（shRNA）和AMPK抑制（化合物C和多柔比星[Dox]）实验表明，ERα-LKB1-AMPK-HNF信号轴的顺序激活对BA的抗HBV效果至关重要。

该研究表明，BA可能通过触发ERα-AMPKα-HNF通路抑制HBV复制，为其对其他病毒的潜在保护机制提供了见解。

附：英文原文

Title: Sequential activation of ERα-AMPKα signaling by the flavonoid baicalin down-regulates viral HNF-dependent HBV replication

Author: 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

Issue&Volume: 2024-10-30

Abstract: 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.

DOI: 10.1038/s41401-024-01408-3

Source: https://www.nature.com/articles/s41401-024-01408-3