Sophoricoside ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy.
AIM
The study aims to evaluate protective effects of sophoricoside (Sop) on cardiac hypertrophy. Meanwhile, the potential and significance of Sop should be broadened and it should be considered as an attractive drug for the treatment of pathological cardiac hypertrophy and heart failure.


METHODS
Using the phenylephrine (PE)-induced neonatal rat cardiomyocytes (NRCMs) enlargement model, the potent protection of Sop against cardiomyocytes enlargement was evaluated. The function of Sop was validated in mice received transverse aortic coarctation (TAC) or sham surgery. At 1 week after TAC surgery, mice were treated with Sop for the following 4 weeks, the hearts were harvested after echocardiography examination.


RESULTS
Our study revealed that Sop significantly mitigated TAC-induced heart dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, Sop treatment induced a remarkable activation of AMPK/mTORC1-autophagy cascade following sustained hypertrophic stimulation. Importantly, the protective effect of Sop was largely abolished by the AMPKα inhibitor Compound C, suggesting an AMPK activation-dependent manner of Sop function on suppressing pathological cardiac hypertrophy.


CONCLUSION
Sop ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy. Hence, Sop might be an attractive candidate for the treatment of pathological cardiac hypertrophy and heart failure.
['Gao|Maomao|M|', 'Hu|Fengjiao|F|', 'Hu|Manli|M|', 'Hu|Yufeng|Y|', 'Shi|Hongjie|H|', 'Zhao|Guo-Jun|GJ|', 'Jian|Chongshu|C|', 'Ji|Yan-Xiao|YX|', 'Zhang|Xiao-Jing|XJ|', 'She|Zhi-Gang|ZG|', 'Li|Hongliang|H|', 'Zhu|Lihua|L|']
D055372:AMP-Activated Protein Kinases D000818:Animals D001343:Autophagy D001578:Benzopyrans D006332:Cardiomegaly D048429:Cell Size D002478:Cells, Cultured D004195:Disease Models, Animal D004789:Enzyme Activation D020536:Enzyme Activators D005355:Fibrosis D008297:Male D000076222:Mechanistic Target of Rapamycin Complex 1 D051379:Mice D032383:Myocytes, Cardiac D017207:Rats, Sprague-Dawley D015398:Signal Transduction
Sophoricoside cardiac hypertrophy AMPK autophagy