Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, No.37 Guoxue Lane, Chengdu 610041, China; Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
Phytomedicine. 2022 Jul 20;102:154153. doi: 10.1016/j.phymed.2022.154153. Epub 2022 May 13.
The cytokine storm (CS) triggered by coronavirus disease 2019 (COVID-19) has caused serious harm to health of humanity and huge economic burden to the world, and there is a lack of effective methods to treat this complication.
In this research, we used network pharmacology and molecular docking to reveal the interaction mechanism in the glycyrrhetinic acid (GA) for the treatment of CS, and validated the effect of GA intervention CS by experiments.
First, we screened corresponding target of GA and CS from online databases, and obtained the action target genes through the Venn diagram. Then, protein-protein interaction (PPI) network, Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the action target genes were acquired by R language to predict its mechanism. Next, molecular docking was performed on core targets. Finally, experiments in which GA intervened in lipopolysaccharide (LPS)-induced CS were implemented.
84 action target genes were obtained from online database. The PPI network of target genes showed that TNF, IL6, MAPK3, PTGS2, ESR1 and PPARG were considered as the core genes. The results of GO and KEGG showed that action target genes were closely related to inflammatory and immune related signaling pathways, such as TNF signaling pathway, IL-17 signaling pathway, Human cytomegalovirus infection, PPAR signaling pathway and so on. Molecule docking results prompted that GA had fine affinity with IL6 and TNF proteins. Finally, in vivo and in vitro experimental results showed that GA could significantly inhibit LPS-induced CS.
GA has a potential inhibitory effect on CS, which is worthy of further exploration.
由 2019 年冠状病毒病（COVID-19）引发的细胞因子风暴（CS）对人类健康造成了严重危害，并给世界带来了巨大的经济负担，目前缺乏有效的治疗这种并发症的方法。
本研究采用网络药理学和分子对接技术，揭示甘草次酸（GA）治疗 CS 的相互作用机制，并通过实验验证 GA 干预 CS 的效果。
首先，我们从在线数据库中筛选出 GA 和 CS 对应的靶标，并通过 Venn 图获得作用靶基因。然后，通过 R 语言获取作用靶基因的蛋白质-蛋白质相互作用（PPI）网络、基因本体（GO）分析和京都基因与基因组百科全书（KEGG）通路富集，以预测其作用机制。接下来，对核心靶标进行分子对接。最后，进行 GA 干预脂多糖（LPS）诱导 CS 的实验。
从在线数据库中获得了 84 个作用靶基因。靶基因的 PPI 网络显示，TNF、IL6、MAPK3、PTGS2、ESR1 和 PPARG 被认为是核心基因。GO 和 KEGG 结果表明，作用靶基因与炎症和免疫相关信号通路密切相关，如 TNF 信号通路、IL-17 信号通路、人巨细胞病毒感染、PPAR 信号通路等。分子对接结果提示 GA 与 IL6 和 TNF 蛋白具有良好的亲和力。最后，体内和体外实验结果表明，GA 能显著抑制 LPS 诱导的 CS。
GA 对 CS 具有潜在的抑制作用，值得进一步探索。
