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[摘要]
目的 基于系統(tǒng)藥理學方法研究雷公藤配伍甘草治療類風濕性關節(jié)炎作用機制。方法 基于中藥系統(tǒng)藥理學平臺(TCMSP)數(shù)據(jù)庫和文獻搜索,建立雷公藤配伍甘草化學成分庫。運用DRAR-CPI、中醫(yī)分子機制的生物信息學分析工具(BATMAN-TCM)等在線預測網(wǎng)站,預測成分靶標,并與疾病靶標取交集得到雷公藤配伍甘草治療類風濕性關節(jié)炎作用靶標。通過作用靶標反向篩選潛在活性成分,并用超高效液相色譜-飛行時間質譜(UPLC-Q-TOF/MS)分析手段對活性成分進行驗證。利用GeneMANIA數(shù)據(jù)庫搜索間接靶標并利用蛋白互作篩選關鍵靶標,采用分子對接技術(SystemsDock)對潛在活性成分和關鍵靶標進行匹配,驗證前期靶標篩選的可靠性以及反向藥效團匹配的正確性。通過GO和京都基因與基因組百科全書通路分析(KEGG)生物學注釋分析關鍵作用通路,探討雷公藤配伍甘草治療類風濕性關節(jié)炎作用機制。結果 共得到33個化學成分和47個潛在靶標,其中32個成分31個靶標和35條通路與藥對治療類風濕性關節(jié)炎有密切關系,主要涉及花生四烯酸代謝通路、白介素(IL)-17信號通路、核因子(NF)-κB信號通路等炎癥通路以及T細胞受體信號通路、C型凝集素受體信號通路等與免疫相關的通路。結論 雷公藤配伍甘草治療類風濕性關節(jié)炎主要通過炎癥與免疫調節(jié)等多條途徑得以實現(xiàn)。
[Key word]
[Abstract]
Objective To explore the mechanism of Triptergium wilfordii combined with Glycyrrhiza uralensis in the treatment of Rheumatoid Arthritis based on systematic pharmacology. Methods TCMSP database and literature search were used to establish the chemical constituents Library of Triptergium wilfordii combined with Glycyrrhiza uralensis. The target of components was predicted through DRAR-CPI, BATMAN-TCM and other online prediction websites,and intersect with disease targets to obtain the therapeutic targets of Triptergium wilfordii combined with Glycyrrhiza uralensis for Rheumatoid Arthritis. Potential active components were screened by reverse targeting and verified by ultra-high performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). GeneMANIA database was used to search indirect targets and protein interaction was used to screen key targets. Molecular docking technology (Systems Dock) was used to match potential active ingredients with key targets to verify the reliability of previous target screening and the correctness of reverse pharmacophore matching. To explore the mechanism of Triptergium wilfordii combined with Glycyrrhiza uralensis in the treatment of rheumatoid arthritis, key pathways were analyzed by GO and KEGG biological annotations. Results A total of 33 chemical constituents and 47 potential targets were obtained. Among them, 31 targets of 32 components and 35 pathways were closely related to drug therapy for Rheumatoid Arthritis, mainly involving the inflammatory pathways such as arachidonic acid metabolic pathway, IL-17 signaling pathway, as well as the immune-related pathways such as NF-κB signaling pathway and T cell receptor signaling pathway. Conclusion The treatment of Triptergium wilfordii combined with Glycyrrhiza uralensis mainly through inflammation and immune regulation.
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