[關(guān)鍵詞]
[摘要]
目的 基于系統(tǒng)藥理學(xué)方法研究雷公藤配伍甘草治療類(lèi)風(fēng)濕性關(guān)節(jié)炎作用機(jī)制。方法 基于中藥系統(tǒng)藥理學(xué)平臺(tái)(TCMSP)數(shù)據(jù)庫(kù)和文獻(xiàn)搜索,建立雷公藤配伍甘草化學(xué)成分庫(kù)。運(yùn)用DRAR-CPI、中醫(yī)分子機(jī)制的生物信息學(xué)分析工具(BATMAN-TCM)等在線(xiàn)預(yù)測(cè)網(wǎng)站,預(yù)測(cè)成分靶標(biāo),并與疾病靶標(biāo)取交集得到雷公藤配伍甘草治療類(lèi)風(fēng)濕性關(guān)節(jié)炎作用靶標(biāo)。通過(guò)作用靶標(biāo)反向篩選潛在活性成分,并用超高效液相色譜-飛行時(shí)間質(zhì)譜(UPLC-Q-TOF/MS)分析手段對(duì)活性成分進(jìn)行驗(yàn)證。利用GeneMANIA數(shù)據(jù)庫(kù)搜索間接靶標(biāo)并利用蛋白互作篩選關(guān)鍵靶標(biāo),采用分子對(duì)接技術(shù)(SystemsDock)對(duì)潛在活性成分和關(guān)鍵靶標(biāo)進(jìn)行匹配,驗(yàn)證前期靶標(biāo)篩選的可靠性以及反向藥效團(tuán)匹配的正確性。通過(guò)GO和京都基因與基因組百科全書(shū)通路分析(KEGG)生物學(xué)注釋分析關(guān)鍵作用通路,探討雷公藤配伍甘草治療類(lèi)風(fēng)濕性關(guān)節(jié)炎作用機(jī)制。結(jié)果 共得到33個(gè)化學(xué)成分和47個(gè)潛在靶標(biāo),其中32個(gè)成分31個(gè)靶標(biāo)和35條通路與藥對(duì)治療類(lèi)風(fēng)濕性關(guān)節(jié)炎有密切關(guān)系,主要涉及花生四烯酸代謝通路、白介素(IL)-17信號(hào)通路、核因子(NF)-κB信號(hào)通路等炎癥通路以及T細(xì)胞受體信號(hào)通路、C型凝集素受體信號(hào)通路等與免疫相關(guān)的通路。結(jié)論 雷公藤配伍甘草治療類(lèi)風(fēng)濕性關(guān)節(jié)炎主要通過(guò)炎癥與免疫調(diào)節(jié)等多條途徑得以實(shí)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.
[中圖分類(lèi)號(hào)]
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