Protective effect of Fisetin against angiotensin II-induced apoptosis by activation of IGF-IR-PI3K-Akt signaling in H9c2 cells and spontaneous hypertension rats

Yeh Peng Chen, Kalaiselvi Sivalingam, Marthandam Asokan Shibu, Rajendran Peramaiyan, Cecilia Hsuan Day, Chia Yao Shen, Chao Hung Lai, Ray Jade Chen, Vijaya Padma Viswanadha, Ya Fang Chen, Chih Yang Huang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Fisetin, a polyphenolic compound, has drawn notable attention owing to its antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. However, the cardiac effects of fisetin are not clear yet. Hypothesis: The aim of the present study is to examine the cardioprotective effect of fisetin against Ang-II induced apoptosis in H9c2 cells and in spontaneous hypertensive rats (SHR). Methods/study design: The in vitro protective effect of fisetin was evaluated after the cells were treated with fisetin (50 µM/ml/ 24 h) for 2 h prior or after Ang-II administration to induce apoptosis. For in vivo experiments, SHRs were orally administered with fisetin (10 mg/kg) twice a week for 6 weeks. Cellular apoptosis was analyzed by TUNEL staining assay and the modulation in the expression levels of proteins involved in apoptosis and cell survival were determined by western blotting. Results: Our results demonstrate the potent cardioprotective efficacy of fisetin against Ang-II induced apoptosis in H9c2 cells and in SHR models. Fisetin administration reduced the apoptotic nuclei considerably And reduced the expression of apoptotic proteins such as TNF- α, Fas L, FADD, Cleaved caspase-3 and Cleaved PARP and increased the cell survival and anti-apoptotic proteins like Bcl-2, Bcl-x L, p-IGF1R, p-PI3K and p-AKT in both in vitro and in vivo models. Conclusion: In conclusion, the results of the present study reveal that fisetin activates the IGF-IR-dependent p-PI3K/p-Akt survival signaling pathway and suppresses the caspase dependent apoptosis.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalPhytomedicine
Volume57
DOIs
Publication statusPublished - Apr 1 2019

Keywords

  • Angiotensin-II
  • Apoptosis
  • Cell survival
  • Fisetin

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine

Fingerprint Dive into the research topics of 'Protective effect of Fisetin against angiotensin II-induced apoptosis by activation of IGF-IR-PI3K-Akt signaling in H9c2 cells and spontaneous hypertension rats'. Together they form a unique fingerprint.

  • Cite this

    Chen, Y. P., Sivalingam, K., Shibu, M. A., Peramaiyan, R., Day, C. H., Shen, C. Y., Lai, C. H., Chen, R. J., Viswanadha, V. P., Chen, Y. F., & Huang, C. Y. (2019). Protective effect of Fisetin against angiotensin II-induced apoptosis by activation of IGF-IR-PI3K-Akt signaling in H9c2 cells and spontaneous hypertension rats. Phytomedicine, 57, 1-8. https://doi.org/10.1016/j.phymed.2018.09.179