Asiatic Acid Protects against Cardiac Hypertrophy through Activating AMPKa Signalling Pathway

作者:Ma, Zhen-Guo; Dai, Jia; Wei, Wen-Ying; Zhang, Wen-Bin; Xu, Si-Chi; Liao, Hai-Han; Yang, Zheng; Tang, Qi-Zhu*
来源:International Journal of Biological Sciences, 2016, 12(7): 861-871.
DOI:10.7150/ijbs.14213

摘要

Background: AMP-activated protein kinase alpha (AMPK alpha) is closely involved in the process of cardiac hypertrophy. Asiatic acid (AA), a pentacyclic triterpene, was found to activate AMPK alpha in our preliminary experiment. However, its effects on the development of cardiac hypertrophy remain unclear. The present study was to determine whether AA could protect against cardiac hypertrophy. Methods: Mice subjected to aortic banding were orally given AA (10 or 30mg/kg) for 7 weeks. In the inhibitory experiment, Compound C was intraperitoneally injected for 3 weeks after surgery. Results: Our results showed that AA markedly inhibited hypertrophic responses induced by pressure overload or angiotensin II. AA also suppressed cardiac fibrosis in vivo and accumulation of collagen in vitro. The protective effects of AA were mediated by activation of AMPK alpha and inhibition of the mammalian target of rapamycin (mTOR) pathway and extracellular signal-regulated kinase (ERK) in vivo and in vitro. However, AA lost the protective effects after AMPK alpha inhibition or gene deficiency. Conclusions: AA protects against cardiac hypertrophy by activating AMPKa, and has the potential to be used for the treatment of heart failure.