Drug repurposing based on the similarity gene expression signatures to explore for potential indications of quercetin: a case study of multiple sclerosis

Frontiers in Chemistry

Chemistry

Xiaofei Chen¹  Hui Zhang¹  Liuqing Yang¹  Mingliang Zhang¹  Yali Wu¹  Bing Han²  Yulong Chen²  Xiaoyan Wang³  Weixia Li³  Jinfa Tang³ 

[1] Henan Province Engineering Research Center for Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, Henan Provincial Key Laboratory for Clinical Pharmacy of Traditional Chinese Medicine, Henan Province Engineering Research Center of Safety Evaluation and Risk Management of Traditional Chinese Medicine, Department of Pharmacy, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China;School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China;School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China;Henan Province Engineering Research Center for Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, Henan Provincial Key Laboratory for Clinical Pharmacy of Traditional Chinese Medicine, Henan Province Engineering Research Center of Safety Evaluation and Risk Management of Traditional Chinese Medicine, Department of Pharmacy, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China;

关键词: natural products;    drug repurposing;    drug discovery;    quercetin;    multiple sclerosis;    medicinal indications;    omics;    experimental verification;   

DOI  :  10.3389/fchem.2023.1250043

 received in 2023-06-29, accepted in 2023-08-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

Quercetin (QR) is a natural flavonol compound widely distributed in the plant kingdom with extensive pharmacological effects. To find the potential clinical indications of QR, 156 differentially expressed genes (DEGs) regulated by QR were obtained from the Gene Expression Omnibus database, and new potential pharmacological effects and clinical indications of QR were repurposed by integrating compounds with similar gene perturbation signatures and associated-disease signatures to QR based on the Connectivity Map and Coexpedia platforms. The results suggested QR has mainly potential therapeutic effects on multiple sclerosis (MS), osteoarthritis, type 2 diabetes mellitus, and acute leukemia. Then, MS was selected for subsequent animal experiments as a representative potential indication, and it found that QR significantly delays the onset time of classical MS model animal mice and ameliorates the inflammatory infiltration and demyelination in the central nervous system. Combined with network pharmacology technology, the therapeutic mechanism of QR on MS was further demonstrated to be related to the inhibition of the expression of inflammatory cytokines (TNF-α, IL-6, IL-1β, IFN-γ, IL-17A, and IL-2) related to TNF-α/TNFR1 signaling pathway. In conclusion, this study expanded the clinical indications of QR and preliminarily confirmed the therapeutic effect and potential mechanism of QR on MS.

【 授权许可】

Unknown   
Copyright © 2023 Chen, Zhang, Li, Wang, Chen, Wu, Zhang, Yang, Han and Tang.