目的 基于網(wǎng)絡(luò)藥理學(xué)及體外實(shí)驗(yàn)研究毛蘭素治療阿爾茨海默病的潛在分子作用機(jī)制。方法 首先通過檢索PubChem、SwissTargetPrediction、citexs數(shù)據(jù)庫，獲取毛蘭素的作用靶點(diǎn)，后利用TTD、PharmGKB、GeneCards、OMIM、GEO、DisGeNET、Celt平臺(tái)檢索阿爾茨海默病的相關(guān)靶點(diǎn)，利用Venny平臺(tái)、STRING數(shù)據(jù)庫、Cytoscape軟件進(jìn)行拓?fù)浞治霁@取毛蘭素治療阿爾茨海默病的核心靶點(diǎn)，利用R語言對(duì)所獲得的交集靶點(diǎn)進(jìn)行基因本體（GO）功能和京都基因和基因百科全書（KEGG）信號(hào)通路富集分析，通過CB-dock2網(wǎng)站進(jìn)行分子對(duì)接，細(xì)胞實(shí)驗(yàn)進(jìn)行驗(yàn)證。結(jié)果 毛蘭素治療阿爾茨海默病的核心靶點(diǎn)為蛋白激酶B1（Akt1）、B細(xì)胞淋巴瘤/白血病-2（Bcl-2）、哺乳動(dòng)物雷帕霉素靶蛋白（mTOR）。GO富集分析顯示與神經(jīng)元凋亡相關(guān)，KEGG通路富集分析得到關(guān)鍵通路為磷脂酰肌醇-3-激酶（PI3K）/Akt信號(hào)通路。分子對(duì)接結(jié)果顯示毛蘭素與3個(gè)核心靶點(diǎn)均具有較好的結(jié)合能力。細(xì)胞實(shí)驗(yàn)結(jié)果表明，與模型組比較，毛蘭素組SH-SY5Y細(xì)胞活性顯著增高，細(xì)胞凋亡程度下降（P＜0.01），且毛蘭素濃度為50 nmol/L時(shí)細(xì)胞活力最高；經(jīng)毛蘭素干預(yù)后，SH-SY5Y細(xì)胞mTOR、細(xì)胞凋亡調(diào)節(jié)因子（Bax）蛋白表達(dá)顯著降低；Bcl-2、p-Akt、Akt、PI3K蛋白表達(dá)顯著升高（P＜0.001）。結(jié)論 毛蘭素可能通過調(diào)控PI3K/Akt信號(hào)通路抑制細(xì)胞凋亡，對(duì)阿爾茨海默癥起到潛在治療效果。

Objective To explore the potential molecular mechanisms of erianin in treatment of Alzheimer's disease based on network pharmacology and in vitro experiments. Methods The targets of erianin were obtained by searching databases such as PubChem, SwissTargetPrediction, and citexs. The relevant targets of Alzheimer's disease were retrieved from databases including TTD, PharmGKB, GeneCards, OMIM, GEO, DisGeNET, and Celt platform. Topological analysis was carried out using Venny platform, STRING database, and Cytoscape software to obtain the core targets of erianin in treatment of Alzheimer's disease. GO functional and KEGG pathway enrichment analyses were performed on the obtained intersection targets using R language. Molecular docking was conducted via the CB-dock2 website, and cell experiments were carried out for verification. Results The core targets of erianin in treatment of Alzheimer's disease were Akt1, Bcl-2, and mTOR. GO enrichment analysis indicated an association with neuronal apoptosis. KEGG pathway enrichment analysis identified the key pathway as the PI3K/Akt signaling pathway. Molecular docking results showed that erianin had good binding ability to the three core targets. Cell experiment results demonstrated that compared with the model group, the viability of SH-SY5Y cells in the erianin group was significantly increased, and the degree of cell apoptosis decreased (P < 0.01), and the cell viability was highest when the concentration of erianin was 50 nmol/L. After erianin intervention, the protein expressions of mTOR and Bax in SH-SY5Y cells were significantly decreased, while the protein expressions of Bcl-2, p-Akt, Akt, and PI3K were significantly increased (P < 0.001). Conclusion Erianin may inhibit cell apoptosis by regulating the PI3K/Akt signaling pathway, showing potential therapeutic effects on Alzheimer’s disease.

R285;R286.1

大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練計(jì)劃項(xiàng)目（國家重點(diǎn)支持領(lǐng)域項(xiàng)目）（202310228063）；大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練項(xiàng)目（國家級(jí)一般項(xiàng)目）（202410228053，202410228015，202410228010）；黑龍江省省屬本科高?！皟?yōu)秀青年教師基礎(chǔ)研究支持計(jì)劃”（YQJH2024224）；黑龍江中醫(yī)藥大學(xué)科研基金項(xiàng)目（博士創(chuàng)新基金）（2019BS05）