目的 基于網(wǎng)絡(luò)藥理學(xué)和分子對接探討關(guān)黃母顆粒治療圍絕經(jīng)期綜合征的分子機(jī)制。方法 通過SymMap、中國天然產(chǎn)物化學(xué)成分庫篩選關(guān)黃母顆粒中構(gòu)成藥物主要化學(xué)成分,而后通過TCMSP數(shù)據(jù)庫以及既往文獻(xiàn)對查詢有效化學(xué)成分的對應(yīng)靶點(diǎn),結(jié)果的匹配規(guī)范通過Uniprot數(shù)據(jù)庫進(jìn)行。運(yùn)用Cytoscape 3.6.0軟件構(gòu)建關(guān)黃母顆粒的藥物-有效成分-作用靶點(diǎn)網(wǎng)絡(luò)。通過DrugBank和GeneCards數(shù)據(jù)庫明確圍絕經(jīng)期綜合征主要疾病靶點(diǎn),并與關(guān)黃母顆粒有效成分靶點(diǎn)進(jìn)行匹配而獲得潛在治療靶點(diǎn)?；贛etascape數(shù)據(jù)庫和DAVID數(shù)據(jù)庫對潛在治療靶點(diǎn)進(jìn)行GO生物過程、KEGG信號通路分析,構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用(PPI)網(wǎng)絡(luò)并應(yīng)用Cytoscape軟件進(jìn)行拓?fù)浞治?應(yīng)用Surflex-Dock進(jìn)行分子對接。結(jié)果 共獲得有效化學(xué)成分86種,通過合并及刪除重復(fù)值后得到有效成分作用靶點(diǎn)298個(gè),關(guān)黃母顆粒治療圍絕經(jīng)期綜合征的潛在靶點(diǎn)基因228個(gè)?；虮倔w論(GO)功能分析得到排名前10名的差異基因主要涉及蛋白質(zhì)代謝、細(xì)胞周期、細(xì)胞器功能、染色體等方面。KEGG富集分析顯示,關(guān)黃母顆粒有效成分治療圍絕經(jīng)期綜合征排名前10的信號通路包括血脂和動脈粥樣硬化通路(lipid and atherosclerosis)、化學(xué)致癌-受體激活通路(chemical carcinogenesis-receptor activation)、磷脂酰肌醇3-激酶(PI3K)-蛋白激酶B(Akt)信號通路等。分子對接結(jié)果顯示,梓醇、五羥黃酮、漢黃芩素、山柰酚、芍藥苷與黏著連接蛋白β1(CTNNB1)、表皮生長因子受體(EGFR)、甘油醛-3-磷酸脫氫酶(GAPDH)、腫瘤壞死因子(TNF)、腫瘤蛋白P53(TP53)具有較好的結(jié)合活性。結(jié)論 關(guān)黃母顆粒可能通過梓醇、五羥黃酮、芍藥苷等成分,通過影響EGFR、TNF及CTNNB1等關(guān)鍵靶點(diǎn)的表達(dá)治療圍絕經(jīng)期綜合征。

Objective To investigate the molecular mechanism of Guanhuangmu Granules in treatment of perimenopausal syndrome based on network pharmacology and molecular docking. Methods The main chemical components of Guanhuangmu Granules were screened by SymMap and Chinese natural product chemical component database, and then the corresponding targets of effective chemical components were queried by TCMSP database and previous literature, and the matching of the results was carried out by Uniprot database. Cytoscape 3.6.0 software was used to construct drug-active component-target network of Guanhuangmu Granules. The main disease targets of perimenopausal syndrome were identified through databases such as DrugBank and GeneCards, and matched with the targets of the active ingredients of Guanhuangmu Granules to obtain potential therapeutic targets. GO biological processes and KEGG signaling pathways were analyzed for potential therapeutic targets based on Metascape database and DAVID database, and protein-protein interaction (PPI) networks were constructed. Molecular docking was performed by Surflex-Dock. Results A total of 86 effective chemical components were obtained, 298 active component targets were obtained by merging and deleting duplicate values, and 228 potential target genes were obtained by Guanhuangmu granules in treatment of perimenopausal syndrome. The top 10 differential genes were mainly involved in protein metabolism, cell cycle, organelle function, and chromosome by gene ontology (GO) functional analysis. KEGG enrichment analysis showed that the top 10 signaling pathways in treatment of perimenopausal syndrome by the active components of Guanhuangmu Granules include lipid and atherosclerosis pathway, chemical carcinogenesis-receptor activation, PI3K-Akt signaling pathway. Molecular docking results showed that catalpol, pentahydroxyflavone, baicalin, kaempferol, paeoniflorin had good binding activities with CTNNB1, EGFR, GAPDH, TNF and TP53. Conclusion Guanhuangmu Granules may treat perimenopausal syndrome by influencing the expression of EGFR, TNF, CTNNB1 and other key targets through paeoniflorin, pentahydroxyflavone, catalpa and other components.

R984

新疆維吾爾自治區(qū)自然科學(xué)基金資助項(xiàng)目(2021D01A42)