背景:大多数COVID-19幸存者患有慢性持续性症状,目前还没有明确的治疗方法。补肺活血(BFHX)胶囊发挥临床效益,而物质基础和分子机制尚不清楚。
目的:本研究旨在阐明BFHX胶囊对COVID-19恢复期的保护机制。采用UHPLC-HRMS和各种数据库来探索潜在的化合物和靶标。PPI,MCODE,转录因子(TF),和miRNA分析进行接收枢纽靶标和相应的上游调节因子.
方法:应用分子对接验证化合物与靶标的结合活性。Further,GO,KEGG,WIKI,进行了反应组分析,并构建了复合目标症状和基因-疾病网络。共获得了127个化合物和313个靶标。筛选了总共10个中心靶标,并显示出与关键化合物的良好结合亲和力。
结果:MLLT1、CBFB、EZH2被确定为关键TFs,和hsa-mir-146a-5p,hsa-mir-26b-5p,和hsa-mir-24-3p被预测为重要的miRNA。BFHX胶囊可能通过靶向TNF缓解症状,IL-6,IFNG,和TGF-β1。此外,BFHX胶囊可能通过调节细胞因子-细胞因子受体的相互作用,对COVID-19恢复期呼吸系统疾病(尤其是肺纤维化和肺部感染)和多系统损害发挥治疗作用,以及TGF-β,TNF,和Toll样受体信号通路。
结论:总之,BFHX胶囊可能通过多种化合物(例如albiflorin,异补骨脂素,和新巴瓦异黄酮),多个靶标(如TNF,IL-6和EGF)和多种途径(TGF-β,TNF,和Toll样受体信号通路)。
BACKGROUND: Most COVID-19 survivors are troubled with chronic persistent symptoms, which have currently no definitive treatments. Bufei Huoxue (BFHX) capsule exerts clinical benefit, while the material basis and molecular mechanism remain unclear.
OBJECTIVE: The study aimed to elucidate the protective mechanisms of BFHX capsules against COVID-19 convalescence. UHPLC-HRMS and various databases were employed to explore potential compounds and targets. PPI, MCODE, transcription factor (TF), and miRNA analyses were conducted to receive hub targets and corresponding upstream regulators.
METHODS: Molecular docking was applied to verify the binding activity of compound and target. Further, GO, KEGG, WIKI, and Reactome analyses were performed, and compound-targetsymptom and gene-disease networks were constructed. A total of 127 compounds and 313 targets were acquired. A sum of 10 hub targets were screened and showed good binding affinities with critical compounds.
RESULTS: MLLT1, CBFB, and EZH2 were identified as key TFs, and hsa-mir-146a-5p, hsa-mir- 26b-5p, and hsa-mir-24-3p were predicted to be important miRNAs. BFHX capsule may alleviate the symptoms by targeting TNF, IL-6, IFNG, and TGF-β1. Besides, BFHX capsule may exert a therapeutic effect on respiratory disease (especially pulmonary fibrosis and lung infection) and multi-system damage during COVID-19 convalescence by regulating cytokine-cytokine receptor interaction, as well as TGF-β, TNF, and Toll-like receptor signaling pathways.
CONCLUSIONS: In summary, BFHX capsule may exert a therapeutic effect on multi-system damages during COVID-19 convalescence through multiple compounds (such as albiflorin, isopsoralen, and neobavaisoflavone), multiple targets (such as TNF, IL-6, and EGF) and multiple pathways (TGF-β, TNF, and Toll-like receptor signaling pathways).