1. Academic Validation
  2. Homoplantaginin attenuates high glucose-induced vascular endothelial dysfunction via inhibiting store-operated calcium entry channel and endoplasmic reticulum stress

Homoplantaginin attenuates high glucose-induced vascular endothelial dysfunction via inhibiting store-operated calcium entry channel and endoplasmic reticulum stress

  • J Pharm Pharmacol. 2023 Sep 29:rgad087. doi: 10.1093/jpp/rgad087.
Yanyan Zhou 1 Lei Wang 1 Yuchen Liu 1 Lili Fan 1 Xueying Zhang 1 Qingru Shi 1 Xulu Li 1 Yining Lin 1 Feihua Wu 1
Affiliations

Affiliation

  • 1 School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Abstract

Objectives: The activation of store-operated calcium entry (SOCE) channel and endoplasmic reticulum stress (ERS) induced by high glucose (HG) is recognized as a major cause of vascular endothelial dysfunction. This study aims to investigate the protective effect of homoplantaginin (Hom) on HG-induced endothelial dysfunction.

Methods: HG-induced vascular endothelial dysfunction model in human umbilical vein endothelial cells (HUVECs) and rat-isolated thoracic aortas were established to observe the protective effect of Hom, further evaluated the mechanism of SOCE channel and ERS in the pathogenesis.

Key findings: Hom increased the levels of nitric oxide (NO) and phospho-endothelial nitric oxide synthase (p-eNOS) in HUVECs and isolated rat thoracic aortas in a dose-dependent manner, restored acetylcholine-mediated endothelium-dependent vasodilation. Network pharmacology showed that the pathogenesis of diabetic vascular complications may involve calcium (Ca2+) signal pathway. Hom reduced Ca2+ concentration via blocking SOCE channel in HUVECs, and resisted ERS activation by down-regulating ERS-related proteins expression. Importantly, SKF96365 (SOCE inhibitor) intervention experiment showed that Hom inhibited ERS activation by blocking the SOCE channel, further increased the levels of NO and p-eNOS.

Conclusion: Hom could alleviate HG-induced vascular endothelial dysfunction by inhibiting SOCE channel and ERS. This provided a potential pharmacological intervention strategy for the treatment of vascular endothelial dysfunction.

Keywords

endoplasmic reticulum stress; endothelial dysfunction; high glucose; homoplantaginin; store-operated calcium entry.

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