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

野鸦胆酸和托尔门蒂克酸通过 PI3K/AKT 或 ERK 1/2 信号通路保护血管内皮细胞免于缺氧诱导的细胞凋亡

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作者:Chaofeng Shi, Zhengchao Li, Yuqiang Wu, Xia Li, Yaxiao Li, Jinxia Wei, JianYu Li, Yongliang Zhang, Lingzhi Li

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.

Significance

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

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