@article{APS10784,
author = {Yang Hong and Wan-qing Xu and Jing Feng and Han Lou and Heng Liu and Lei Wang and Hao Cui and Lin-tong Jiang and Ran-chen Xu and Heng-hui Xu and Min-zhen Xie and Yang Li and Philipp Kopylov and Qi Wang and Yong Zhang},
title = {Nitidine chloride induces cardiac hypertrophy in mice by targeting autophagy-related 4B cysteine peptidase},
journal = {Acta Pharmacologica Sinica},
volume = {44},
number = {3},
year = {2023},
keywords = {},
abstract = {Nitidine chloride (NC) is a standard active component from the traditional Chinese medicine Zanthoxylum nitidum (Roxb.) DC. (ZN). NC has shown a variety of pharmacological activities including anti-tumor activity. As a number of anti-tumor drugs cause cardiotoxicity, herein we investigated whether NC exerted a cardiotoxic effect and the underlying mechanism. Aqueous extract of ZN (ZNE) was intraperitoneally injected into rats, while NC was injected into beagles and mice once daily for 4 weeks. Cardiac function was assessed using echocardiography. We showed that both ZNE administered in rats and NC administered in mice induced dose-dependent cardiac hypertrophy and dysfunction, whereas administration of NC at the middle and high dose caused death in Beagles. Consistently, we observed a reduction of cardiac autophagy levels in NC-treated mice and neonatal mouse cardiomyocytes. Furthermore, we demonstrated that autophagy-related 4B cysteine peptidase (ATG4B) may be a potential target of NC, since overexpression of ATG4B reversed the cardiac hypertrophy and reduced autophagy levels observed in NC-treated mice. We conclude that NC induces cardiac hypertrophy via ATG4B-mediated downregulation of autophagy in mice. Thus, this study provides guidance for the safe clinical application of ZN and the use of NC as an anti-tumor drug.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10784}
}