Qian Huiqin, Jin Qianqian, Liu Yichen, Wang Ning, Chu Yuru, Liu Bingbing, Liu Yan, Jiang Wanli, Song Yong
College of Pharmacy, Sanquan College of Xinxiang Medical University, Xinxiang 453000, China.
Otolaryngological Department, Puyang Oilfield General Hospital, Puyang 457000, China.
Evid Based Complement Alternat Med. 2020 Aug 4;2020:9873739. doi: 10.1155/2020/9873739. eCollection 2020.
Sanmiao pill (SMP), a Chinese traditional formula, had been used to treat gouty arthritis (GA). However, the active compounds and underlying mechanism remained unclear. Hence, network pharmacology and molecular docking were utilized to explore bioactive compounds and potential mechanism of action of SMP in treating GA. In the study, the compounds of SMP, corresponding targets, and GA-related targets were mined from various pharmacological databases. Then, herb-compound-target, compound-target, PPI, and target-pathway networks were constructed. Ultimately, molecular docking was carried out to verify the predicted results. The results indicated that 47 active compounds, 338 targets, and 144 disease targets were collected. Network analysis implied that Schneid. played a vital role in the whole formula. Moreover, 7 compounds (quercetin, kaempferol, wogonin, rutaecarpine, baicalein, beta-sitosterol, and stigmasterol) and 4 targets (NFKB1, RELA, MAPK1, and TNF) might be the kernel compounds and targets of SMP against GA. According to GOBP and KEGG pathway enrichment analysis and target-pathway network, SMP might exert a therapeutic role in GA by regulating numerous biological processes and pathways, including lipopolysaccharide-mediated signaling pathway, positive regulation of transcription, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, NOD-like receptor signaling pathway, and MAPK signaling pathway. The results of molecular docking showcased that 11 pairs of compound with targets had tight binding strength. Thereinto, 4 compounds of MAPK1 and 5 compounds of NFKB1 possessed a better combination, suggesting that MAPK1 and NFKB1 might be considered as therapeutic targets in treatment of GA. This study verified that SMP had synergistic effect on GA by multicomponents, multitargets, and multipathways.
三妙丸（SMP）是一种中药传统配方，一直用于治疗痛风性关节炎（GA）。然而，其活性成分和潜在机制仍不清楚。因此，利用网络药理学和分子对接技术来探索SMP治疗GA的生物活性成分和潜在作用机制。在本研究中，从各种药理学数据库中挖掘出SMP的化合物、相应靶点以及GA相关靶点。然后，构建了草药-化合物-靶点、化合物-靶点、蛋白质-蛋白质相互作用（PPI）和靶点-通路网络。最终，进行分子对接以验证预测结果。结果表明，共收集到47种活性化合物、338个靶点和144个疾病靶点。网络分析表明，威灵仙在整个配方中起着至关重要的作用。此外，7种化合物（槲皮素、山奈酚、汉黄芩素、吴茱萸碱、黄芩素、β-谷甾醇和豆甾醇）和4个靶点（NFKB1、RELA、MAPK1和TNF）可能是SMP抗GA的核心化合物和靶点。根据基因本体生物学过程（GOBP）和京都基因与基因组百科全书（KEGG）通路富集分析以及靶点-通路网络，SMP可能通过调节众多生物过程和通路发挥对GA的治疗作用，包括脂多糖介导的信号通路、转录的正调控、Toll样受体信号通路、JAK-STAT信号通路、NOD样受体信号通路和MAPK信号通路。分子对接结果显示，11对化合物与靶点具有紧密的结合强度。其中，MAPK1的4种化合物和NFKB1的5种化合物具有更好的结合，表明MAPK1和NFKB1可能被视为GA治疗的靶点。本研究证实SMP通过多成分、多靶点和多通路对GA具有协同作用。
