基于网络药理学和分子对接技术探讨升阳益胃汤治疗新型冠状病毒肺炎作用机制

Mechanism of Shengyang Yiwei Decoction(升阳益胃汤)Against COVID-19 Based on Network Pharmacology and Molecular Docking

目的运用网络药理学和分子对接技术研究升阳益胃汤治疗新型冠状病毒肺炎(COVID-19)的作用机制。方法在中药系统药理学数据库与分析平台(TCMSP)中检索该复方所具有的活性成分和作用靶点。在GeneCards、OMIM数据库中,以"corona virus disease 2019"为关键词筛选疾病基因。通过Cyoscape3.7.1软件构建"药物-成分-靶点-疾病"网络图,对筛选出的基因靶点进行GO功能富集分析和KEGG信号通路富集分析,并进行分子对接实验,预测其作用机制。结果筛选出升阳益胃汤的活性成分270个,与COVID-19的交集靶点23个,对应活性成分108个,活性成分以槲皮素、山柰酚、β-谷甾醇、汉黄芩素、异鼠李素为主,可作用于NOS2、DPP4、NOS3、CASP3等靶点,GO富集得到32条条目,KEGG富集到74条信号通路,如病毒性心肌炎、PI3K-Akt信号通路、细胞凋亡等,主要涉及抗炎、抗纤维化、免疫调节、抑制细胞凋亡、抑制病毒复制、抑制细胞因子风暴等方面。分子对接结果显示,槲皮素、汉黄芩素与IL-6的最佳结合能分别为-2.38 kcal/mol、-3.36 kcal/mol,低于利托那韦、利巴韦林的最佳结合能,可自主结合并形成较稳定的结构。结论升阳益胃汤是通过多通路、多靶点发挥对COVID-19的治疗作用。推测其作用机制可能主要是通过槲皮素、汉黄芩素作用于IL-6等靶点,经PI3K-Akt信号通路参与抗炎、抗纤维化进而达到对COVID-19的治疗作用。其他活性成分如山柰酚、β-谷甾醇等也可作用于NOS2、NOS3、CASP3等靶点参与抗炎、免疫调节、抑制细胞凋亡、抑制病毒复制、抑制细胞因子风暴等过程,发挥对COVID-19的辅助治疗作用。

Objective To study the mechanism of Shengyang Yiwei Decoction(升阳益胃汤)in the treatment of corona virus disease 2019(COVID-19)by network pharmacology and molecular docking.Methods The active components and targets of Shengyang Yiwei Decoction were searched in TCMSP."Corona virus disease 2019"was used as the key word to screen disease genes in genecards and OMIM databases.Through Cyoscape3.7.1 software,the network diagram of"drug-composition-target-disease"was constructed to analyze the key targets and signal pathways,and the molecular docking experiment was carried out to predict its mechanism.Results 270 active componentswere screened out,and 23 intersection targets related to COVID-19 were identified.Quercetin,kaempferol,β-sitosterol,wogonin and isorhamnetin were the main active components among the corresponding 108 active components,which could act on the targets of NOS2,DPP4,NOS3,CASP3,etc.32 entries were obtained from GO enrichment.KEGG was enriched in 74 signaling pathways,such as viral myocarditis,PI3 K-Akt signaling pathway,apoptosis and so on,which mainly involved anti-inflammatory,anti fibrosis,immune regulation,inhibition of cell apoptosis,inhibition of virus replication,inhibition of cytokine storm and so on.The results of molecular docking showed that the binding energies of quercetin and wogonin with IL-6 were-2.38 kcal/mol and-3.36 kcal/mol,respectively,which could bind independently and form a stable structure.Conclusion Shengyang Yiwei Decoction has therapeutic effect on COVID-19 through multiple pathways and targets.It is speculated that quercetin and wogonin may act on IL-6 and other targets,and participate in anti-inflammatory and anti fibrosis through PI3 K-Akt signaling pathway,and then achieve the therapeutic effect on COVID-19.Other active ingredients such as kaempferol andβ-sitosterol can also act on the targets of NOS2,NOS3,CASP3,etc.,and participate in the process of anti-inflammatory,immune regulation,inhibition of cell apoptosis,inhibition of virus replication,inhibition of cytokine storm,etc.,and play an auxiliary therapeutic role in COVID-19.