五味子（Schisandra Chinensis Turcz）是一种中药，具有补肾安神、益气生津的功能。它可以用于治疗失眠、健忘、滑精、咳嗽，以及肝肾阴阳虚的综合症。现代药理学研究表明，五味子具有调节宿主免疫力、抗癌、抗病毒和保肝作用。然而，五味子调节抗病毒免疫的具体机制尚不清楚。我们旨在探索五味子活性成分在抗病毒免疫中的治疗效果，并进一步研究其潜在机制。采用免疫印迹、实时荧光定量PCR、酶联免疫吸附试验、免疫荧光及免疫沉淀等技术，研究五味子中最丰富、生物活性最强的成分五味子醇C（SC）对cGAS-STING信号通路的激活及其机制。此外，还采用相关质膜蛋白A介导的STING激活和水力动力注射介导的HBV重复小鼠模型，研究SC对STING信号通路的激活和其体内抗病毒作用。研究发现，SC促进cGAS-STING通路的激活，伴随着干扰素β（IFN β）和下游基因表达的增加。此外，SC还发挥抗HBV作用，在水力动力注射介导的HBV重复小鼠模型中减少HBeAg、HBcAg、HBsAg和HBV DNA水平，并提高IFN β的产生和干扰素诱导基因（IFIT1、ISG15和CXCL10）的表达。从机理上讲，SC可以促进TANK结合激酶1（TBK1）和STING之间的相互作用，这对IRF3的磷酸化和IFN β的产生非常重要。我们的研究确认了SC增强cGAS-STING通路的激活并抑制HBV复制的作用，同时为采用SC治疗慢性乙型肝炎和其他传染性疾病提供了线索。Copyright © 2023. Published by Elsevier B.V.

Schisandra Chinensis (Turcz.) Baill. is a long-term used traditional Chinese medicine with the functions of tonifying the kidney and calming the heart, tonifying qi and engendering fluid. It can be used to treat insomnia and dreaminess, spermatorrhea, coughs, as well as liver and kidney deficiency of Yin or Yang Syndrome. Modern pharmacological studies have shown that Schisandra Chinensis regulates host immunity and exhibits anti-cancer, antiviral and liver-protecting effects. However, the specific mechanism by which Schisandra Chinensis modulates antiviral immunity is unknown.We sought to explore the therapeutic effect of the active components of Schisandra Chinensis on anti-viral immunity and further investigate the underlying mechanism.Immunoblotting, quantitative real-time PCR, enzyme-linked immunosorbent assay, immunofluorescence, and immunoprecipitation were used to investigate the effect of schisandrin C (SC), one of the most abundant and biologically active components of Schisandra Chinensis, on the activation of cGAS-STING signaling pathway and the underlying mechanism. In addition, CMA-mediated STING activation and hydrodynamic injection-mediated HBV-replicating mouse model were used to investigate the effect of SC on the activation of STING signaling pathway and its antiviral effect in vivo.SC promoted cGAS-STING pathway activation, accompanied by increased production of interferon β (IFN β) and downstream gene expression. Moreover, SC also exerted anti-HBV effects, reducing HBeAg, HBcAg, HBsAg, and HBV DNA levels in hydrodynamic injection-mediated HBV-replicating mouse model and elevating the production of IFN β and expression of interferon-stimulated genes (IFIT1, ISG15, and CXCL10). Mechanistically, SC could facilitate the interaction between TANK-binding kinase 1 (TBK1) and STING, which is important for IRF3 phosphorylation and production of IFN β.Our study confirmed that SC enhances cGAS-STING pathway activation and inhibits HBV replication, as well as provides clues for chronic hepatitis B and other infectious diseases treated by SC.Copyright © 2023. Published by Elsevier B.V.