[關(guān)鍵詞]
[摘要]
目的 運(yùn)用網(wǎng)絡(luò)藥理學(xué)技術(shù)探討逍遙散與文拉法辛聯(lián)用抗抑郁的作用機(jī)制。方法 通過TCMSP、PubChem、OMIM、GeneCards以及UniProt等數(shù)據(jù)庫獲得逍遙散和文拉法辛治療抑郁癥的作用靶點(diǎn);利用STRING網(wǎng)站得到蛋白互作網(wǎng)絡(luò);并通過Metascape網(wǎng)站對潛在作用靶點(diǎn)進(jìn)行富集分析;使用Cytoscape軟件繪制“靶點(diǎn)-成分-通路”可視化網(wǎng)絡(luò)圖。結(jié)果 逍遙散主要通過芍藥苷、刺槐素、兒茶素、槲皮素等化學(xué)成分和文拉法辛聯(lián)合作用發(fā)揮抗抑郁作用。逍遙散和文拉法辛治療抑郁癥的相關(guān)靶點(diǎn)共208個(gè),主要為酪氨酸蛋白激酶(SRC)、信號(hào)轉(zhuǎn)導(dǎo)和轉(zhuǎn)錄激活器3(STAT3)、轉(zhuǎn)錄因子AP-1(JUN)、絲裂原活化蛋白激酶3(MAPK3)等。這些主要靶點(diǎn)作用于糖尿病并發(fā)癥中的AGE-RAGE信號(hào)通路(AGE-RAGE signaling pathway in diabetic complications)、癌癥通路(pathways in cancer)等43條通路,調(diào)節(jié)對受損的應(yīng)答(response to wounding)、對無機(jī)物的應(yīng)答(response to inorganic substance)以及細(xì)胞成分運(yùn)動(dòng)的正向調(diào)節(jié)(positive regulation of cellular component movement)、血液循環(huán)(blood circulation)和有機(jī)羥基化合物代謝過程(organic hydroxy compound metabolic process)等生物學(xué)過程發(fā)揮抗抑郁作用。結(jié)論 逍遙散與文拉法辛聯(lián)用通過多靶點(diǎn)、多通路發(fā)揮抗抑郁作用,利用網(wǎng)絡(luò)藥理學(xué)預(yù)測中西藥聯(lián)合治療疾病的作用機(jī)制值得深入探討。
[Key word]
[Abstract]
Objectives To investigate the anti-depressant mechanisms of Xiaoyao San combined with venlafaxine by using network pharmacological techniques. Methods The targets of Xiaoyao San and venlafaxine on depression were obtained through the TCMSP database, PubChem database, OMIM database, GeneCards database, and Uniprot database. The protein interaction network was obtained by using the String website. The potential targets were enriched through the Metascape website. Cytoscape software was used to draw the visual network diagram of "target-component-pathway". Results In combination of venlafaxine, Xiaoyao San exhibited anti-depression effects through paeoniflorin, robinin, catechin, quercetin and other chemical constituents. There were 208 related targets of Xiaoyao San and venlafaxine in the treatment of depression, mainly including tyrosine protein kinase, signal transducers and transcriptional activators 3, transcription factor AP-1, mitogen-activated protein kinase 3. These main targets play an anti-depressant role via regulating 43 pathways, such as AGE-RAGE signaling pathway in diabetic complications, pathways in cancer, and influencing biological processes, such as response to wounding, response to inorganic substance, positive regulation of cellular component movement, blood circulation, organic hydroxy compound metabolic process. Conclusions The combination of Xiaoyao San and venlafaxine plays an anti-depressant role through multi-targets and multi-pathways. It is worthy to deeply explore the underlying mechanisms of the combined effects of Chinese and western medicines by network pharmacology.
[中圖分類號(hào)]
R285.5
[基金項(xiàng)目]
國家自然科學(xué)基金青年基金項(xiàng)目(81803962);山西省留學(xué)回國人員科技活動(dòng)擇優(yōu)資助項(xiàng)目(20200013)