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

Abdur Rehman; Israr Fatima; Yinuo Wang; Jiapei Tong; Fatima Noor; Muhammad Qasim; Yuzhong Peng; Mingzhi Liao

doi:10.1016/j.compbiomed.2023.107424

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

Comput Biol Med. 2023 Oct:165:107424. doi: 10.1016/j.compbiomed.2023.107424. Epub 2023 Sep 10.

Authors

Abdur Rehman¹, Israr Fatima¹, Yinuo Wang¹, Jiapei Tong², Fatima Noor³, Muhammad Qasim³, Yuzhong Peng⁴, Mingzhi Liao⁵

Affiliations

¹ Center of Bioinformatics, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.
² College of Information Engineering, Northwest A&F University, Yangling, Shaanxi, 712100, China.
³ Department of Bioinformatics and Biotechnology, Government College University Faisalabad, 38000, Pakistan.
⁴ Key Lab of Scientific Computing and Intelligent Information Processing in Universities of Guangxi, Nanning Normal University, Nanning, 530001, China. Electronic address: jedison@163.com.
⁵ Center of Bioinformatics, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China. Electronic address: liaomingzhi83@163.com.

PMID: 37717527
DOI: 10.1016/j.compbiomed.2023.107424

Abstract

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-namely quebrachamine,corynan-17-ol, stemmadenine,strictanol,rhazinilam, and rhazimolare-to impede ccRCC progression by modulating the activity of MMP9,ACE,ERBB2, and HSP90AA1 genes. Further, molecular docking and dynamic simulations confirmed the plausible binding affinities of these compounds. Despite these promising findings, we recognize the need for comprehensive in vivo and in vitro studies to further investigate the pharmacokinetics and biosafety profiles of these compounds.

Keywords: Clear cell renal cell carcinoma; Molecular docking; Molecular dynamic simulation; Phytochemicals; Rhazya stricta.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apocynaceae*
Carcinoma, Renal Cell* / drug therapy
Carcinoma, Renal Cell* / genetics
Kidney Neoplasms* / drug therapy
Kidney Neoplasms* / genetics
Matrix Metalloproteinase 9
Molecular Docking Simulation
Prospective Studies

Substances

Matrix Metalloproteinase 9