Sophoricoside ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy

Abstract

Aim: The study aims to evaluate protective effects of sophoricoside (Sop) on cardiac hypertrophy. Meanwhile, The potential and significance of clinical transformation of Sop should be broadened and it should be firmly supported as an attractive drug for the treatment of pathological cardiac hypertrophy and heart failure. Methods: Using the phenylephrine (PE)-induced neonatal rat cardiomyocytes (NRCMs) hypertrophy 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 one 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 stimulated. 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.

Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism

“…Next, we focused on dissecting whether there is a deep-seated common molecular target to explain how FGF21 regulates the nuclear translocation of NF-κB and Nrf2. AMPK is a trimeric serine/threonine protein kinase activated in the form of phosphorylation and considered to be a converter that regulates cell energy metabolism (Gao et al 2020 ). Activated AMPK regulates glucose and lipid metabolism to reduce ATP consumption and increase ATP production, meeting cellular energy needs to prevent inflammatory response and oxidative stress caused cell death (Herzig and Shaw 2018 ).…”

Fibroblast Growth Factor 21 Attenuates Salt-sensitive Hypertension-induced Nephropathy Through Anti-inflammation and Anti-oxidation Mechanism

“…Next, we focused on dissecting whether there is a deep-seated common molecular target to explain how FGF21 regulates the nuclear translocation of NF-κB and Nrf2. AMPK is a trimeric serine / threonine protein kinase activated in the form of phosphorylation and considered to be a converter that regulates cell energy metabolism (Gao, Hu et al, 2020). Activated AMPK regulates glucose and lipid metabolism to reduce ATP consumption and increase ATP production, meeting cellular energy needs to prevent in ammatory response and oxidative stress caused cell death (Herzig and Shaw, 2018).…”

Impaired autophagy as an etiological factor of various disease entities

“…Wykazano m. in. zmniejszenie przerostów kardiomiocytów w przebiegu przerostu mięśnia sercowego w wyniku leczenia soforikozydem, który aktywował szlak AMPK/ mTORC1, indukując proces autofagii [43]. Innym przykładem jest zastosowanie metforminy, która poprzez blokowanie szlaku aktywującego autofagię, zależną od kinazy AMP, zmniejszała rozwój niewydolności serca [44].…”