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. 2020 Jul 1:252:117666.
doi: 10.1016/j.lfs.2020.117666. Epub 2020 Apr 13.

Euscaphic acid and Tormentic acid protect vascular endothelial cells against hypoxia-induced apoptosis via PI3K/AKT or ERK 1/2 signaling pathway

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Euscaphic acid and Tormentic acid protect vascular endothelial cells against hypoxia-induced apoptosis via PI3K/AKT or ERK 1/2 signaling pathway

Chaofeng Shi et al. Life Sci. .

Abstract

Aims: Euscaphic acid and Tormentic acid are aglycones of Kaji-ichigoside F1 and Rosamultin, respectively. These four compounds are pentacyclic triterpenoid, isolated from the subterranean root of the Potentilla anserina L. Based on the protective roles against hypoxia-induced apoptosis of Euscaphic acid and Tormentic acid in vascular endothelial cells, this study was designed to determine the mechanisms.

Main methods: The model of hypoxic injuries in EA. hy926 cells was established. Through applications of PI3K/AKT inhibitor, LY294002 and ERK1/2 inhibitor, PD98059, we explored the relationships between pharmacodynamic mechanisms and PI3K/AKT or ERK 1/2 signaling pathway. The anti-hypoxic effects were studied by methyl-thiazolyl-tetrazolium (MTT) assay, Hematoxylin-Eosin (HE) staining, DAPI staining, and flow cytometry. The mechanisms of anti-mitochondrial apoptosis were explored by western blot. The expressions of p-ERK 1/2, ERK 1/2, p-AKT, AKT, p-NF-κB, NF-κB, Bcl-2, Bax, Cyt C, cleaved caspase-9 and cleaved caspase-3 were detected.

Key findings: Euscaphic acid protected vascular endothelial cells against hypoxia-induced apoptosis via ERK1/2 signaling pathway, and Tormentic acid brought its efficacy into full play via PI3K/AKT and ERK1/2 signaling pathways. In addition, PI3K/AKT signaling pathway positively regulated ERK1/2 pathway, and ERK1/2 pathway negatively regulated PI3K/AKT pathway.

Significance: This evidence provides theoretical and experimental basis for the following research on anti-hypoxic drugs of Potentilla anserina L.

Keywords: Apoptosis; ERK 1/2 signaling pathway; Euscaphic acid; Hypoxia; PI3K/AKT signaling pathway; Tormentic acid.

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Conflict of interest statement

Declaration of competing interest The authors declare that there are no conflicts of interest.

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