Unveiling the multi-target compounds of Rhazya stricta: Discovery and inhibition of novel target genes for the treatment of clear cell renal cell carcinoma

作者：Abdur Rehman, Israr Fatima, Yinuo Wang, Jiapei Tong, Fatima Noor, Muhammad Qasim, Yuzhong Peng, Mingzhi Liao · 发表于：Computers in Biology and Medicine · 年份：2023 · DOI：10.1016/j.compbiomed.2023.107424 · 被引用次数：11 · 研究领域：Alkaloids: synthesis and pharmacology、Pharmacogenetics and Drug Metabolism、Hormonal Regulation and Hypertension

Clear cell renal cell carcinoma (ccRCC) is a prevalent kidney malignancy with a pressing need for innovative therapeutic strategies. In this context, emerging research has focused on exploring the medicinal potential of plants such as Rhazya stricta. Nevertheless, the complex molecular mechanisms underlying its potential therapeutic efficacy remain largely elusive. Our study employed an integrative approach comprising data mining,network pharmacology,tissue cell type analysis, and molecular modelling approaches to identify potent phytochemicals from R. stricta, with potential relevance for ccRCC treatments. Initially, we collected data on R. stricta's phytochemical from public databases. Subsequently, we integrated this information with differentially expressed genes (DEGs) in ccRCC, which were derived from microarray datasets(GSE16441,GSE66270, and GSE76351). We identified potential intersections between R. stricta and ccRCC targets, which enabled us to construct a compound-genes-pathway network using Cytoscape software. This helped illuminate R. stricta's multi-target pharmacological effects on ccRCC. Moreover, tissue cell type analysis added another layer of insight into the cellular specificity of potential therapeutic targets in the kidney. Through further Kaplan-Meier survival analysis, we pinpointed MMP9,ACE,ERBB2, and HSP90AA1 as prospective diagnostic and prognostic biomarkers for ccRCC. Notably, our study underscores the potential of R. stricta derived compounds-nam...