基于网络药理学及实验验证探究清开灵软胶囊治疗冠状病毒肺炎的作用机制

Mechanisms of Qingkailing soft capsules against coronavirus pneumonia based on network pharmacology and experimental verification

目的通过网络药理学分析和基于湿热疫毒袭肺病证结合小鼠模型的实验验证,对清开灵软胶囊治疗冠状病毒肺炎的作用机制进行初步探索。方法从建库开始截至2022年6月28日,通过TCMSP数据库和文献挖掘获得清开灵软胶囊主要活性成分,利用Swiss Target Prediction、GeneCards数据库获得清开灵软胶囊治疗冠状病毒肺炎的潜在靶点,构建PPI互作网络和“药物-成分-靶点”网络,对潜在靶点进行KEGG Pathway富集分析。基于湿热疫毒袭肺小鼠病证结合模型,检测清开灵软胶囊对肺指数的影响,Elisa法检测用药后肺组织中IL-6、SOD和下丘脑中PGE2、CAMP含量的变化。结果筛选出清开灵软胶囊活性成分78个,潜在靶点112个。“药物-成分-靶点”网络中包含296条边,7个药物节点,槲皮素等33个化合物节点,表皮生长因子受体等112个靶点节点,涉及卡波西肉瘤相关疱疹病毒感染通路、PI3K-AKT等信号通路。与模型组相比,清开灵软胶囊组肺指数明显降低(P<0.01),肺组织中IL-6、下丘脑中PGE2的含量也显著降低(P<0.01)。结论清开灵软胶囊可能通过调节炎症介质和发热介质,对冠状病毒肺炎发挥治疗作用。

Objective To study the targets and signal pathways of Qingkailing soft capsules in the treatment of coronavirus pneumonia based on network pharmacology.Methods The main chemical ingredients of Qingkailing soft capsules were obtained by searching the TCMSP database for related literature that was published between inception and June 28,2022.The potential targets of Qingkailing soft capsules in the treatment of coronavirus pneumonia were obtained from Swiss Target Prediction and GeneCards database.A PPI interaction network and“drug-component-target”network were constructed before the potential targets were analyzed via KEGG pathway enrichment.The effect of Qingkailing soft capsules on lung indexes was detected,and the contents of IL-6,SOD in lung tissues and those of PGE2 and CAMP in the hypothalamus were detected by Elisa.Results The“drug-component-target”network consisted of 296 edges,7 drug nodes,33 compound nodes and 112 target nodes.Compared with the model group,the lung indexes of the Qingkailing soft capsule group decreased significantly(P<0.01),so did the contents of IL-6 in lung tissues and PGE2 in the hypothalamus(P<0.01).Conclusion Qingkailing soft capsules may play a role in the treatment of coronavirus pneumonia by regulating inflammatory mediators and febrile mediators.