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

  • Life Sci. 2020 Jul 1;252:117666. doi: 10.1016/j.lfs.2020.117666.
Chaofeng Shi  1 ,  Zhengchao Li  2 ,  Yuqiang Wu  3 ,  Xia Li  3 ,  Yaxiao Li  3 ,  Jinxia Wei  3 ,  JianYu Li  3 ,  Yongliang Zhang  4 ,  Lingzhi Li  5
Affiliations
  • 1. Department of Pharmacy, Logistics University of Chinese People's Armed Police Forces, Tianjin, China; Medical Team, Zhoukou Detachment of Chinese People's Armed Police Forces, Henan, China.
  • 2. Characteristic Medical Center of Chinese People's Armed Police Forces, Tianjin, China.
  • 3. Department of Pharmacy, Logistics University of Chinese People's Armed Police Forces, Tianjin, China.
  • 4. Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin, China. Electronic address: [email protected].
  • 5. Department of Pharmacy, Logistics University of Chinese People's Armed Police Forces, Tianjin, China; Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin, China. Electronic address: [email protected].
PMID: 32298737 DOI: 10.1016/j.lfs.2020.117666
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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