Yeh-Peng Chen1, Kalaiselvi Sivalingam2, Marthandam Asokan Shibu2, Rajendran Peramaiyan2, Cecilia Hsuan Day3, Chia-Yao Shen3, Chao-Hung Lai4, Ray-Jade Chen5, Vijaya Padma Viswanadha6, Ya-Fang Chen7, Chih-Yang Huang8. 1. Ph.D. Program for Aging, China Medical University, Taichung, Taiwan; Division of Cardiology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan. 2. Graduate Institute of Basic Medical Science, China Medical University, Taichung, 40402, Taiwan. 3. Department of Nursing, MeiHo University, Pingtung, 91202, Taiwan. 4. Division of Cardiology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan. 5. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan. 6. Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, India. 7. Department of Obstetrics and Gynecology, Taichung Veteran's General Hospital, Taichung, 40705, Taiwan. 8. Graduate Institute of Basic Medical Science, China Medical University, Taichung, 40402, Taiwan; School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; Department of Biotechnology, Asia University, Taichung, 41354, Taiwan. Electronic address: cyhuang@mail.cmu.edu.tw.
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-xL, 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.
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-xL, 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.