小陷胸汤治疗新冠肺炎的机制探讨

Mechanism Exploration of Xiaoxianxiong Decoction in the Treatment of SARS-CoV-2

传统药方小陷胸汤及其加减化裁方可用于新型冠状病毒肺炎的临床治疗,但其抗炎有效成分及作用机制尚不清楚.首先通过网络药理学筛选小陷胸汤的活性成分,其次在细胞水平上探究其对免疫细胞的调控效果,最后从分子水平验证其治疗新冠肺炎的可能性.实验结果表明:小陷胸汤治疗新冠肺炎可能是通过槲皮素、黄芩素、β-谷甾醇、香叶木素等活性成分调节CD4^(+)T细胞以及CD4^(+)/CD8^(+)比值,起到抗炎、调节自身免疫反应的作用.黄芩素很可能通过与新冠病毒关键蛋白3CLpro(Mpro)的关键位点结合,从而抑制3CLpro的复制功能,进而达到抗病毒的作用.槲皮素可能通过提高调节性T细胞分化程度降低肺部炎症情况.香叶木素可通过改变巨噬细胞分化情况以及提升NK细胞比例来增强机体固有免疫,起到治疗肺炎的作用.

As a traditional prescription,Xiaoxianxiong Decoction and its verified prescriptions are used in the clinical treatment for COVID19(Corona Virus Disease 2019).Though it has broad practical basis,the mechanism of its anti-inflammatory active ingredients is still unobscured.Along with the development of genomics and proteomics,massive amounts of bioinformatics data can be used to analyze the mechanism of drug-disease in the protein,molecular,and genetic levels.Active ingredients of Xiaoxianxiong Decoction were screened through network pharmacology,its regulatory effect on immune cells was explored,and its possibility of treating COVID-19 at the molecular level was further verified.The results showed that main activated components of Xiaoxianxiong Decoction to treat COVID-19 were quercetin,baicalein,β-sitosterol,diosmetin.Those active ingredients could up-regulate level of CD4^(+)T cells and the ratio of CD4^(+)/CD8^(+)to regulate excessiveimmune response.The study also suggested that Baicalein could inhibit the replication function of 3CLpro by binding to the critical site of 3CLpro,an essential protein of the new coronavirus,and achieving antiviral effect.Quercetin could reduce lung inflammation by improving the differentiation of regulatory T cells.Diosmetin could enhance human innate immunity by regulating the differentiation of macrophages and increasing the proportion of NK cells,thus playing a role in the treatment of COVID-19.