Frontiers in Pharmacology (Oct 2022)

Quercetin inhibits angiotensin II-induced vascular smooth muscle cell proliferation and activation of JAK2/STAT3 pathway: A target based networking pharmacology approach

  • Di Wang,
  • Di Wang,
  • Di Wang,
  • Farman Ali,
  • Farman Ali,
  • Farman Ali,
  • Huixin Liu,
  • Huixin Liu,
  • Huixin Liu,
  • Ying Cheng,
  • Ying Cheng,
  • Ying Cheng,
  • Meizhu Wu,
  • Meizhu Wu,
  • Meizhu Wu,
  • Muhammad Zubair Saleem,
  • Huifang Zheng,
  • Huifang Zheng,
  • Huifang Zheng,
  • Lihui Wei,
  • Lihui Wei,
  • Lihui Wei,
  • Jiangfeng Chu,
  • Jiangfeng Chu,
  • Jiangfeng Chu,
  • Qiurong Xie,
  • Qiurong Xie,
  • Qiurong Xie,
  • Aling Shen,
  • Aling Shen,
  • Aling Shen,
  • Jun Peng,
  • Jun Peng,
  • Jun Peng

DOI
https://doi.org/10.3389/fphar.2022.1002363
Journal volume & issue
Vol. 13

Abstract

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The rapid growth of vascular smooth muscle cells (VSMCs) represents crucial pathological changes during the development of hypertensive vascular remodeling. Although quercetin exhibits significantly therapeutic effects on antihypertension, the systematic role of quercetin and its exact mode of action in relation to the VSMCs growth and its hypertension-related networking pharmacology is not well-documented. Therefore, the effect of quercetin was investigated using networking pharmacology followed by in vitro strategies to explore its efficacy against angiotensin II (Ang II)-induced cell proliferation. Putative genes of hypertension and quercetin were collected using database mining, and their correlation was investigated. Subsequently, a network of protein-protein interactions was constructed and gene ontology (GO) analysis was performed to identify the role of important genes (including CCND1) and key signaling pathways [including cell proliferation and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway]. We therefore further investigated the effects of quercetin in Ang II-stimulated VSMCs. This current research revealed that quercetin significantly reduced the cell confluency, cell number, and cell viability, as well as expression of proliferating cell nuclear antigen (PCNA) in Ang II-stimulated VSMCs. Mechanistic study by western blotting confirmed that quercetin treatment attenuated the activation of JAK2 and STAT3 by reducing its phosphorylation in Ang II stimulated VSMCs. Collectively, the current study revealed the inhibitory effects of quercetin on proliferation of Ang II stimulated VSMCs, by inhibiting the activation of JAK2/STAT3 signaling might be one of underlying mechanisms.

Keywords