目的 通過網(wǎng)絡(luò)藥理學(xué)探討柴胡皂苷a在抑郁癥治療中的作用機制。方法 從PubChem、PharmMapper和SwissTarget Prediction數(shù)據(jù)庫中獲取柴胡皂苷a的分子結(jié)構(gòu)和潛在靶點。將柴胡皂苷a和抑郁癥的共同靶點導(dǎo)入STRING 11.0數(shù)據(jù)庫，構(gòu)建蛋白相互作用（PPI）網(wǎng)絡(luò)。利用DAVID 6.8數(shù)據(jù)庫進行基因本體論（GO）和京都基因與基因組百科全書（KEGG）富集分析。結(jié)果 本研究共獲得柴胡皂苷a靶點408個，抑郁相關(guān)靶點3 799個，最終得到200個共同靶點，包括白蛋白（ALB）、絲氨酸/蘇氨酸蛋白激酶B（Akt1）、熱休克蛋白90 α家族A類成員1（HSP90AA1）、轉(zhuǎn)錄信號轉(zhuǎn)導(dǎo)和激活因子3（STAT3）和表皮生長因子受體（EGFR）等。GO和KEGG富集分析表明，癌癥、脂質(zhì)和動脈粥樣硬化、前列腺癌、癌癥蛋白多糖、內(nèi)分泌耐藥、叉頭框-O（FoxO）信號通路、磷酸肌醇-3激酶（PI3K）/Akt信號通路、EGFR酪氨酸激酶抑制劑耐藥、Th17細胞分化、催乳素信號通路等通路在柴胡皂苷a抗抑郁中發(fā)揮了重要作用。結(jié)論 柴胡皂苷a可能通過作用于FoxO、催乳素、PI3K/Akt信號通路及ALB、Akt1、HSP90AA1、STAT3等靶點發(fā)揮抗抑郁作用。

Objective To elucidate the mechanism of saikosaponin a in treating depression with network pharmacology. Methods Molecular structure and potential targets of saikosaponin a was obtained from PubChem, PharmMapper and SwissTarget Prediction databases. The common targets of saikosaponin a and depression were imported to the STRING 11.0 database, and then a protein interaction network was constructed. GO and KEGG enrichment were analyzed with DAVID 6.8 database.Results A total of 408 targets of saikosaponin a were obtained and there were 3 799 depression-related targets. A total of 200 common genes were selected as targets of depression including ALB, Akt1, HSP90AA1, STAT3, and EGFR. GO and KEGG analysis suggested that pathways in cancer, lipid and atherosclerosis, prostate cancer, proteoglycans in cancer, endocrine resistance, FoxO signaling pathway, PI3K/Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, Th17 cell differentiation, and prolactin signaling pathway played an imported role. Conclusion Our results suggested that saikosaponin a may exert its antidepressant effect by acting on FoxO, prolactin, and PI3K/Akt signaling pathways and ALB, Akt1, HSP90AA1, and STAT3 targets.

R285;R286.1

陜西省自然科學(xué)基礎(chǔ)研究計劃（2024JC-YBMS-119，2021JQ-816）；陜西省教育廳重點科學(xué)研究計劃項目（高校工程研究中心項目）（24JR162）；陜西基礎(chǔ)科學(xué)（化學(xué)、生物學(xué)）研究院基礎(chǔ)科學(xué)研究計劃（22JHQ050）