目的 基于網絡藥理學結合分子對接技術探究石榴皮治療腹瀉的作用機制。方法 通過TCMSP數據庫獲取石榴皮的活性成分和潛在作用靶點；GeneCards、OMIM、DisGeNET數據庫進行檢索獲得腹瀉的潛在作用靶點，篩選兩者交集靶點；應用Cytoscape軟件構建蛋白相互作用（PPI）圖并篩選核心靶點。通過DAVID數據庫進行基因本體（GO）功能和京都基因與基因組百科全書（KEGG）通路富集分析，最后采用AutoDock軟件進行分子對接驗證。結果 獲得7個石榴皮主要化學成分，石榴皮與腹瀉共同靶點114個。PPI分析顯示，腫瘤抗原p53（TP53）、蛋白激酶B1（Akt1）、腫瘤壞死因子（TNF）、白細胞介素-6（IL-6）、胱天蛋白酶33（CASP）等可能為治療關鍵靶點。通過KEGG分析表明，石榴皮可能通過癌癥通路、磷脂酰肌醇3-激酶（PI3K）/Akt信號通路等起到治療腹瀉的作用。分子對接表明關鍵活性成分與核心靶點均可自發(fā)結合。結論 通過網絡藥理學和分子對接技術揭示石榴皮可以通過多成分、多靶點、多途徑治療腹瀉，為后續(xù)研究提供理論依據。

Objective To explore the mechanism of pomegranate peel in treatment of diarrhea based on network pharmacology and molecular docking technology. Methods The active chemical components of pomegranate peel and the corresponding targets were obtained from TCMSP databases, and the disease targets of diarrhea were retrieved using GeneCards, OMIM, and DisGeNET database, following by filtering the intersection of the two. Cytoscape 3.9.1 software was used to construct the PPI network of the intersection targets and screen the core targets. DAVID database was used for gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of potential targets of pomegranate peel in treatment of diarrhea, and AutoDock software was used for further verified by molecular docking. Results 7 Main chemical constituents of pomegranate peel were screened out, and 114 intersection targets between pomegranate peel and diarrhea were obtained. Topology analysis of PPI network showed that pomegranate peel alleviated diarrhea mainly acting the core targets TP53, Akt1, TNF, IL-6, CASP3, etc. The KEGG enrichment analysis showed that pomegranate peel might play a therapeutic role through the cancer pathway, PI3K/Akt signaling pathway, and so on. Molecular docking showed that the key active ingredients and the core targets could all bind spontaneously. Conclusion Network pharmacology combined with molecular docking proved that pomegranate peel could treat diarrhea through multi-component, multi-target and multi-pathway, which provides theoretical basis for its further in-depth research.

R285

山東省重點研發(fā)計劃項目(2022TZXD0019)