Phytomedicine : international journal of phytotherapy and phytopharmacology · 2023
Astragaloside IV mitigates hypoxia-induced cardiac hypertrophy through calpain-1-mediated mTOR activation.
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Zhang Jingliang, Lu Meili, Li Cong, Yan Bingju, Xu Fang, Wang Hongxin, Zhang Yingjie, Yang Yuhong
Аннотация
BACKGROUND: Astragaloside IV (AsIV), a key functioning element of Astragalus membranaceus, has been recognized for its potential cardiovascular protective properties. However, there is a need to elucidate the impacts of AsIV on myocardial hypertrophy under hypoxia conditions and its root mechanisms.
PURPOSE: This study scrutinized the influence of AsIV on cardiac injury under hypoxia, with particular emphasis on the role of calpain-1 (CAPN1) in mediating mTOR pathways.
METHODS: Hypoxia-triggered cardiac hypertrophy was examined in vivo with CAPN1 knockout and wild-type C57BL/6 mice and in vitro with H9C2 cells. The impacts of AsIV, 3-methyladenine, and CAPN1 inhibition on hypertrophy, autophagy, apoptosis, [Ca2+]i, and CAPN1 and mTOR levels in cardiac tissues and H9C2 cells were investigated.
RESULTS: Both AsIV treatment and CAPN1 knockout mitigated hypoxia-induced cardiac hypertrophy, autophagy, and apoptosis in mice and H9C2 cells. Moreover, AsIV, 3-methyladenine, and CAPN1 inhibition augmented p-mTOR level but reduced [Ca2+]i and CAPN1 level. Additionally, lentivirus-mediated CAPN1 overexpression in H9C2 cells exacerbated myocardial hypertrophy, apoptosis, and p-mTOR inhibition under hypoxia. Specifically, AsIV treatment reversed the impacts of increased CAPN1 expression on cardiac injury and the inhibition of p-mTOR.
CONCLUSION: These findings suggest that AsIV may alleviate cardiac hypertrophy under hypoxia by attenuating apoptosis and autophagy through CAPN1-mediated mTOR activation.
PURPOSE: This study scrutinized the influence of AsIV on cardiac injury under hypoxia, with particular emphasis on the role of calpain-1 (CAPN1) in mediating mTOR pathways.
METHODS: Hypoxia-triggered cardiac hypertrophy was examined in vivo with CAPN1 knockout and wild-type C57BL/6 mice and in vitro with H9C2 cells. The impacts of AsIV, 3-methyladenine, and CAPN1 inhibition on hypertrophy, autophagy, apoptosis, [Ca2+]i, and CAPN1 and mTOR levels in cardiac tissues and H9C2 cells were investigated.
RESULTS: Both AsIV treatment and CAPN1 knockout mitigated hypoxia-induced cardiac hypertrophy, autophagy, and apoptosis in mice and H9C2 cells. Moreover, AsIV, 3-methyladenine, and CAPN1 inhibition augmented p-mTOR level but reduced [Ca2+]i and CAPN1 level. Additionally, lentivirus-mediated CAPN1 overexpression in H9C2 cells exacerbated myocardial hypertrophy, apoptosis, and p-mTOR inhibition under hypoxia. Specifically, AsIV treatment reversed the impacts of increased CAPN1 expression on cardiac injury and the inhibition of p-mTOR.
CONCLUSION: These findings suggest that AsIV may alleviate cardiac hypertrophy under hypoxia by attenuating apoptosis and autophagy through CAPN1-mediated mTOR activation.