[關(guān)鍵詞]
[摘要]
目的 通過整合網(wǎng)絡(luò)藥理學(xué)和網(wǎng)絡(luò)毒理學(xué),探究合歡皮抗焦慮的治療機制和導(dǎo)致腎損傷的致毒機制。方法 基于ETCM、TCMID和BATMAN-TCM數(shù)據(jù)庫收集合歡皮化學(xué)成分,并通過文獻(xiàn)檢索對合歡皮的生物活性成分進(jìn)行篩選和補充。基于PharmMapper、SwissTargetPrediction、BATMAN-TCM和ETCM數(shù)據(jù)庫獲取成分對應(yīng)靶點;在CTD和GeneCards數(shù)據(jù)庫中檢索得到焦慮癥和腎毒性相關(guān)靶點,分別與藥物靶點取交集得到藥效和毒性共有靶點;將共有靶點導(dǎo)入STRING數(shù)據(jù)庫進(jìn)行蛋白互作分析,在Cytoscape軟件進(jìn)行可視化分析;采用STRING數(shù)據(jù)庫進(jìn)行GO生物分析和KEGG通路富集分析。結(jié)果 篩選得到生物活性成分共51個,對應(yīng)靶點747個,其與焦慮癥和腎毒性交集靶點分別為134、144個,相關(guān)通路分別為173、184條。合歡皮可通過調(diào)控cAMP、RAS、MAPK、雌激素、催乳素、甲狀腺激素和TNF等信號途徑治療焦慮癥;其腎毒性的產(chǎn)生與BCL2、SOD靶點以及VEGF、MAPK、mTOR、PI3K-Akt、HIF-1、TNF、Toll-like、NOD-like等信號通路關(guān)系密切。結(jié)論 發(fā)現(xiàn)合歡皮抗焦慮成分主要為木脂素及黃酮類化合物,致毒成分主要為皂苷類化合物。抗焦慮作用可能通過影響神經(jīng)遞質(zhì)5-HT以及下丘腦-垂體-腎上腺(HPA)軸、下丘腦-垂體-性腺(HPG)軸、下丘腦-垂體-甲狀腺(HPT)軸發(fā)揮作用,并通過誘導(dǎo)炎癥反應(yīng)、缺氧狀態(tài)、異常凋亡、氧化應(yīng)激反應(yīng)和自噬失衡產(chǎn)生腎毒性。
[Key word]
[Abstract]
Objective To explore the anxiolytic effects mechanism and nephrotoxicity mechanism of Albizia Cortex by integrating network pharmacology and network toxicology. Methods The chemical components of Albizia Cortex was collected from ETCM, TCMID and BATMAN-TCM databases. The bioactive constituents of Albizia Cortex were screened and supplemented by literature search. The corresponding targets were obtained from PharmMapper, SwissTargetPrediction, BATMAN-TCM and ETCM databases. The anxiety disorder targets and nephrotoxicity targets which were obtained from the CTD and GeneCards databases were intersected with drugs targets separately and introduced into the STRING database to construct the protein interaction network diagram. Visual analysis was carried out in Cytoscape, and GO biological process and KEGG enrichment analysis were carried out in the STRING database. Results A total of 51 bioactive compounds were obtained, corresponding to 747 targets. There were 134 cross-targets and 173 related pathways in anxiety, 144 cross-targets and 184 related pathways in nephrotoxicity. The results show that the Albizia Cortex could regulate the cAMP, Ras, MAPK, Estrogen, Prolactin, Thyroid hormone and TNF pathways to treat anxiety disorders. Nephrotoxicity is closely related to BCL2, SOD targets and VEGF, MAPK, mTOR, PI3K-Akt, HIF-1,TNF,Toll-like, NODlike pathways. Conclusion The study found that the anxiolytic components of Albizia Cortex were mainly lignans and flavonoids, and the toxic components were mainly saponins. The anxiolytic effect probably influenced the 5-HT and HPA, HPG, HPT, and induce nephrotoxicity by inducing inflammation, hypoxia, abnormal apoptosis, oxidative stress and autophagy imbalance.
[中圖分類號]
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