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

3 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

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Phosphatidylinositol 3-Kinases
Angiotensin II
Apoptosis
Hypertension
Cell Survival
fisetin
Apoptosis Regulatory Proteins
In Situ Nick-End Labeling
Neuroprotective Agents
Caspases
Caspase 3
Proteins
Anti-Inflammatory Agents
Antioxidants
Western Blotting
Staining and Labeling

Keywords

  • Angiotensin-II
  • Apoptosis
  • Cell survival
  • Fisetin

ASJC Scopus subject areas

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

Cite this

Protective effect of Fisetin against angiotensin II-induced apoptosis by activation of IGF-IR-PI3K-Akt signaling in H9c2 cells and spontaneous hypertension rats. / Chen, Yeh Peng; Sivalingam, Kalaiselvi; Shibu, Marthandam Asokan; Peramaiyan, Rajendran; Day, Cecilia Hsuan; Shen, Chia Yao; Lai, Chao Hung; Chen, Ray Jade; Viswanadha, Vijaya Padma; Chen, Ya Fang; Huang, Chih Yang.

In: Phytomedicine, Vol. 57, 01.04.2019, p. 1-8.

Research output: Contribution to journalArticle

Chen, Yeh Peng ; Sivalingam, Kalaiselvi ; Shibu, Marthandam Asokan ; Peramaiyan, Rajendran ; Day, Cecilia Hsuan ; Shen, Chia Yao ; Lai, Chao Hung ; Chen, Ray Jade ; Viswanadha, Vijaya Padma ; Chen, Ya Fang ; Huang, Chih Yang. / Protective effect of Fisetin against angiotensin II-induced apoptosis by activation of IGF-IR-PI3K-Akt signaling in H9c2 cells and spontaneous hypertension rats. In: Phytomedicine. 2019 ; Vol. 57. pp. 1-8.
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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.",
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T1 - Protective effect of Fisetin against angiotensin II-induced apoptosis by activation of IGF-IR-PI3K-Akt signaling in H9c2 cells and spontaneous hypertension rats

AU - Chen, Yeh Peng

AU - Sivalingam, Kalaiselvi

AU - Shibu, Marthandam Asokan

AU - Peramaiyan, Rajendran

AU - Day, Cecilia Hsuan

AU - Shen, Chia Yao

AU - Lai, Chao Hung

AU - Chen, Ray Jade

AU - Viswanadha, Vijaya Padma

AU - Chen, Ya Fang

AU - Huang, Chih Yang

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

KW - Angiotensin-II

KW - Apoptosis

KW - Cell survival

KW - Fisetin

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DO - 10.1016/j.phymed.2018.09.179

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