A Novel Compound, Tanshinol Borneol Ester, Ameliorates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Oxidative Stress via the mTOR/β-TrCP/NRF2 Pathway

一种新型化合物丹参醇冰片酯通过 mTOR/β-TrCP/NRF2 通路抑制氧化应激,改善压力超负荷引起的心脏肥大

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作者:Dongjian Han, Fuhang Wang, Bo Wang, Zhentao Qiao, Xinyue Cui, Yi Zhang, Qingjiao Jiang, Miaomiao Liu, Jiahong Shangguan, Xiaohui Zheng, Yajun Bai, Chunyan Du, Deliang Shen

Abstract

Tanshinol borneol ester (DBZ) exerts anti-atherosclerotic and anti-inflammatory effects. However, its effects on cardiac hypertrophy are not well understood. In this work, we investigated the treatment effects and potential mechanisms of DBZ on the hypertrophic heart under oxidative stress and endoplasmic reticulum (ER) stress. A hypertrophic model was established in rats using transverse-aortic constriction (TAC) surgery and in neonatal rat cardiomyocytes (NRCMs) using angiotensin II (Ang II). Our results revealed that DBZ remarkably inhibited oxidative stress and ER stress, blocked autophagy flow, and decreased apoptosis in vivo and in vitro through nuclear NRF2 accumulation, and enhanced NRF2 stability via regulating the mTOR/β-TrcP/NRF2 signal pathway. Thus, DBZ may serve as a promising therapeutic for stress-induced cardiac hypertrophy.

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