Phytomedicine Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India.
Nanomedicine Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India.
Appl Biochem Biotechnol. 2023 Jan;195(1):152-171. doi: 10.1007/s12010-022-04111-3. Epub 2022 Sep 6.
The present study identified the probable mechanism behind the anti-cancer activity of the hexane fraction of Pleurotus osteratus (HFPO) using network pharmacology and experimental validation. HFPO myco-metabolites targets and targets related to the cancer were mined from the online web server, and overlapping targets were screened. Out of the 74 overlapping targets, 33 targets were identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of cancer. Furthermore, the main active myco-metabolites and hub targets were identified by network analysis of the compound-targets network and protein-protein interaction (PPI), respectively. Molecular docking results showed good binding affinity of the hub targets with their respective myco-metabolites. HFPO induced in-vitro anti-cancer activity by affecting the PI3K-AKT-mTOR pathway, besides time-dependent cell cytotoxicity and apoptotic cell body formation. Additionally, tumor volume reduction was observed in HFPO-treated Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice. Overall, HFPO induces anti-cancer potential by modulating the PI3K-AKT-mTOR signaling pathway.
本研究采用网络药理学和实验验证的方法，确定了糙皮侧耳（Pleurotus osteratus）正己烷部分（HFPO）抗癌活性的可能机制。从在线网络服务器中挖掘出 HFPO 真菌代谢产物的靶点和与癌症相关的靶点，并筛选出重叠靶点。在 74 个重叠靶点中，有 33 个靶点被鉴定为癌症的京都基因与基因组百科全书（KEGG）通路。此外，通过化合物-靶点网络和蛋白质-蛋白质相互作用（PPI）的网络分析，分别鉴定出主要的活性真菌代谢产物和枢纽靶点。分子对接结果表明，枢纽靶点与其各自的真菌代谢产物具有良好的结合亲和力。HFPO 通过影响 PI3K-AKT-mTOR 通路，在体外诱导抗癌活性，同时还表现出时间依赖性的细胞毒性和凋亡细胞形态的形成。此外，在 HFPO 处理的瑞士白化病小鼠的艾氏腹水癌（EAC）中观察到肿瘤体积减小。综上所述，HFPO 通过调节 PI3K-AKT-mTOR 信号通路诱导抗癌潜能。
