Formononetin ameliorates high glucose‑induced endothelial dysfunction by inhibiting the JAK/STAT signaling pathway

  • Authors:
    • Zhen Zhou
    • Xinjian Zhou
    • Youhong Dong
    • Mingyi Li
    • Yancheng Xu
  • View Affiliations

  • Published online on: July 19, 2019     https://doi.org/10.3892/mmr.2019.10512
  • Pages: 2893-2901
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Abstract

High glucose‑induced endothelial Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling is associated with the development and progression of the vascular complications of diabetes. The present study aimed to investigate whether formononetin, a biologically active compound isolated from Astragalus membranaceus (Fisch.) Bge, was able to regulate the JAK/STAT signaling pathway, improving endothelial function. In the present study, formononetin was identified to act as a JAK2 inhibitor, similarly to tyrphostin AG 490 (AG490), by significantly inhibiting the phosphorylation and the mRNA expression levels of JAK2 and STAT in HUVECs exposed to high glucose levels. In addition, formononetin and AG490 improved the viability of HUVECs and inhibited the protein expression levels of caspase‑3. Furthermore, formononetin and AG490 attenuated the inflammatory response in HUVECs by downregulating the protein and mRNA expression levels of interleukin (IL)‑1β and intercellular adhesion molecule 1 (ICAM‑1). Formononetin and AG490 also restored nitric oxide (NO) synthesis in HUVECs. Notably, formononetin was able to reverse the abnormal levels of phosphorylated (p)‑JAK2, p‑STAT3, IL‑1β, ICAM‑1 and NO induced by cotreatment with high glucose and IL‑6, an agonist of the JAK/STAT signaling pathway. Additionally, the present results suggested that formononetin restored phenylephrine‑mediated contraction and acetylcholine‑induced relaxation in aortic tissues of rats fed a high‑glucose diet, in a dose‑dependent manner. Collectively, formononetin could improve endothelial function under glucose stress in vivo and in vitro, suggesting that formononetin may represent a novel potential therapeutic compound to treat diabetic vascular complications.

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APA
Zhou, Z., Zhou, X., Dong, Y., Li, M., & Xu, Y. (2019). Formononetin ameliorates high glucose‑induced endothelial dysfunction by inhibiting the JAK/STAT signaling pathway. Molecular Medicine Reports, 20, 2893-2901. https://doi.org/10.3892/mmr.2019.10512
MLA
Zhou, Z., Zhou, X., Dong, Y., Li, M., Xu, Y."Formononetin ameliorates high glucose‑induced endothelial dysfunction by inhibiting the JAK/STAT signaling pathway". Molecular Medicine Reports 20.3 (2019): 2893-2901.
Chicago
Zhou, Z., Zhou, X., Dong, Y., Li, M., Xu, Y."Formononetin ameliorates high glucose‑induced endothelial dysfunction by inhibiting the JAK/STAT signaling pathway". Molecular Medicine Reports 20, no. 3 (2019): 2893-2901. https://doi.org/10.3892/mmr.2019.10512