目的 利用網(wǎng)絡(luò)藥理學(xué)方法研究黃芩治療白癜風(fēng)的作用靶點(diǎn)和機(jī)制。方法 使用中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫(kù)與分析平臺(tái)(TCMSP)篩選得到黃芩中的活性成分及其作用靶點(diǎn),通過(guò)SwissTargetPrediction數(shù)據(jù)庫(kù)檢索補(bǔ)充各個(gè)活性成分的作用靶點(diǎn);通過(guò)OMIM、GeneCards數(shù)據(jù)庫(kù)獲取白癜風(fēng)的相關(guān)靶點(diǎn),與活性成分作用靶點(diǎn)取交集;將黃芩活性成分和白癜風(fēng)的交集靶點(diǎn)導(dǎo)入String數(shù)據(jù)庫(kù)構(gòu)建靶點(diǎn)間的蛋白相互作用(PPI)網(wǎng)絡(luò);利用Cytoscape 3.9.1軟件,構(gòu)建"黃芩-活性成分-白癜風(fēng)靶點(diǎn)"網(wǎng)絡(luò)并篩選核心靶點(diǎn);使用Metascape數(shù)據(jù)庫(kù)對(duì)潛在作用靶點(diǎn)進(jìn)行基因本體論(GO)功能富集分析和京都基因與基因組百科全書(shū)(KEGG)通路富集分析;使用AutoDockTools 1.5.7軟件進(jìn)行分子對(duì)接驗(yàn)證并使用PyMol軟件對(duì)結(jié)果進(jìn)行可視化處理。結(jié)果 共篩選得到黃芩素、漢黃芩素、刺槐素、木蝴蝶素a、表小檗堿、去甲漢黃芩素、5,7,4'-三羥基-8-甲氧基黃酮等36個(gè)活性成分,作用于3 868個(gè)潛在靶點(diǎn),白癜風(fēng)相關(guān)靶點(diǎn)1 349個(gè),黃芩-白癜風(fēng)的交集靶點(diǎn)113個(gè);PPI網(wǎng)絡(luò)分析得到腫瘤蛋白P53(TP53)、絲氨酸/蘇氨酸蛋白激酶1(AKT1)、信號(hào)轉(zhuǎn)導(dǎo)和轉(zhuǎn)錄激活因子3(STAT3)、腫瘤壞死因子(TNF)、絲裂原活化蛋白激酶1(MAPK1)、白細(xì)胞介素-6(IL-6)、胱天蛋白酶3(CASP3)、雌激素受體(ESR1)共8個(gè)核心作用靶點(diǎn);GO和KEGG富集分析顯示,黃芩治療白癜風(fēng)主要涉及胰腺癌、內(nèi)分泌抵抗、神經(jīng)營(yíng)養(yǎng)素信號(hào)通路、細(xì)胞凋亡、乙型肝炎、細(xì)胞衰老等信號(hào)通路。分子對(duì)接結(jié)果顯示黃芩素、漢黃芩素、刺槐素、木蝴蝶素a、表小檗堿、去甲漢黃芩素、5,7,4'-三羥基-8-甲氧基黃酮7個(gè)核心成分與核心靶點(diǎn)具有較好的結(jié)合能。結(jié)論 黃芩可能通過(guò)調(diào)控內(nèi)分泌、神經(jīng)、細(xì)胞衰老和凋亡以及炎癥等方面發(fā)揮治療白癜風(fēng)的作用,為后續(xù)研究黃芩治療白癜風(fēng)提供參考。

Objective To study the target and mechanism of Scutellariae Radix in treatment of vitiligo by means of network pharmacology. Methods The active components and their action targets of Scutellariae Radix were screened by using the traditional Chinese Medicine system Pharmacology Database and Analysis platform (TCMSP), and the action targets of each active component were searched and supplemented by SwissTargetPrediction database. The related targets of vitiligo were obtained through OMIM and GeneCards databases, and the action targets of active components were intersected. The intersection of active components of Scutellaria baicalensis and vitiligo was introduced into String database to construct protein interaction (PPI) network. Using Cytoscape 3.9.1 software, the network of "Scutellariae Radix active ingredient-vitiligo target" was constructed and the core targets were screened. GO functional enrichment analysis and KEGG pathway enrichment analysis of potential targets were carried out by using Metascape database. AutoDockTools1.5.7 software was used for molecular docking verification and PyMol software was used to visualize the results. Results A total of 36 active components, including baicalein, wogonin, sophorin, sophorin a, epiberberine, demethylwogonin, 5 maestrin, trihydroxy-8-methoxy flavonoid, were screened, which acted on 3 868 potential targets, 1 349 targets related to vitiligo and 113targets for the intersection of Scutellaria baicalensis-vitiligo. PPI network analysis showed 8 core targets:TP53, AKT1, STAT3, TNF, MAPK1, IL-6, CASP3, ESR1. GO and KEGG enrichment analysis showed that Scutellariae Radix in the treatment of vitiligo mainly involved pancreatic cancer, endocrine resistance, neurotrophin signal pathway, apoptosis, hepatitis B, cell senescence and other signal pathways. The results of molecular docking showed that the seven core components of baicalein, wogonin, sophorin, sophorin a, epiberberine, demethylated wogonin and 5-methoxy-4-hydroxy-8-methoxy flavonoids had good binding energy with core targets. Conclusion Scutellariae Radix may play a role in treatment of vitiligo by regulating endocrine, nerve, cell senescence, apoptosis and inflammation, which provides a reference for the follow-up study of Scutellariae Radix in the treatment of vitiligo.

R986

國(guó)家重點(diǎn)研發(fā)計(jì)劃項(xiàng)目(2018YFC1706500)