2. Academic Validation
  3. 3,5-Dicaffeoylquinic acid protects H9C2 cells against oxidative stress-induced apoptosis via activation of the PI3K/Akt signaling pathway

3,5-Dicaffeoylquinic acid protects H9C2 cells against oxidative stress-induced apoptosis via activation of the PI3K/Akt signaling pathway

  • Food Nutr Res. 2018 Oct 12;62. doi: 10.29219/fnr.v62.1423.
Yi-Ming Bi 1 2,  Yu-Ting Wu 1 2,  Ling Chen 1 2,  Zhang-Bin Tan 1 2,  Hui-Jie Fan 1 2,  Ling-Peng Xie 1 2,  Wen-Tong Zhang 1 2,  Hong-Mei Chen 1 2,  Jun Li 1 2,  Bin Liu 2 3,  Ying-Chun Zhou 1 2
Affiliations

Affiliations

  • 1 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
  • 2 Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 3 Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
PMID: 30349447 DOI: 10.29219/fnr.v62.1423
Abstract

Background: Oxidative stress-induced Apoptosis plays an important role in the development of heart failure. 3,5-Dicaffeoylquinic acid (3,5-diCQA), a phenolic compound, has shown protective effects against oxidative stress in many diseases.

Objective: The objective of this study was to investigate the anti-apoptosis potential of 3,5-diCQA in cardiomyocyte cells under oxidative stress and explore its underlying mechanisms.

Design: A model of tert-butyl hydroperoxide (TBHP)-induced Apoptosis in a cardiomyocyte cell line (H9C2) was established. Cell viabilities on cell lines were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. The Apoptosis was measured by hoechst33342 and propidium iodide (PI) fluorescent staining. PI (in red) stained the regions of cell apoptosis; Hoechet33342 (in blue) stained the nuclei. The Western blot was used to determine the expressions of related proteins such as p-PI3K: phosphorylated phosphatidylinositol-3-kinase (p-PI3K), phosphorylated Serine and Threonine kinase Akt (p-AKT), p-PTEN, Bcl-2, Bax, and Caspase-3. Afterward, a PI3K Inhibitor, LY294002, was applied to confirm the influence of the PI3K/Akt pathway on TBHP-treated cells of 3,5-diCQA. Then, H9C2 cells were pre-incubated with 3,5-diCQA alone to determine if the expression of activated PI3K/Akt signaling was mediated by 3,5-diCQA in H9C2 cells.

Results: The results showed that TBHP resulted in an increase in cardiomyocyte Apoptosis, whereas 3,5-diCQA treatment protected cells from TBHP-induced Apoptosis in a dose-dependent manner. Moreover, 3,5-diCQA decreased expressions of Bax and Caspase-3 but increased the phosphorylation levels of PI3K and Akt in TBHP-treated cells, which are the key molecules mediating cell survival, whereas Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) phosphorylation was unchanged. Importantly, pre-incubation with a PI3K Inhibitor (LY294002) partly abolished the anti-apoptosis effects of 3,5-diCQA. Further, 3,5-diCQA enhanced the phosphorylation levels of PI3K and Akt in H9C2 cells directly, while LY294002 attenuated the effects of 3,5-diCQA on PI3K and Akt.

Conclusion: This study suggested that 3,5-diCQA rescued myocardium from Apoptosis by increasing the activation of the PI3K/Akt signaling pathway.

Keywords

3,5-dicaffeoylquinic acid; PI3K/Akt pathway; apoptosis; cardiomyocyte; oxidative stress.

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