Baicalin alleviates angiotensin II‐induced cardiomyocyte apoptosis and autophagy and modulates the AMPK/mTOR pathway

Abstract

AbstractAs a main extraction compound from Scutellaria baicalensis Georgi, Baicalin exhibits various biological activities. However, the underlying mechanism of Baicalin on hypertension‐induced heart injury remains unclear. In vivo, mice were infused with angiotensin II (Ang II; 500 ng/kg/min) or saline using osmotic pumps, followed by intragastrically administrated with Baicalin (5 mg/kg/day) for 4 weeks. In vitro, H9C2 cells were stimulated with Ang II (1 μM) and treated with Baicalin (12.5, 25 and 50 μM). Baicalin treatment significantly attenuated the decrease in left ventricular ejection fraction and left ventricular fractional shortening, increase in left ventricular mass, left ventricular systolic volume and left ventricular diastolic volume of Ang II infused mice. Moreover, Baicalin treatment reversed 314 differentially expressed transcripts in the cardiac tissues of Ang II infused mice, and enriched multiple enriched signalling pathways (including apoptosis, autophagy, AMPK/mTOR signalling pathway). Consistently, Baicalin treatment significantly alleviated Ang II‐induced cell apoptosis in vivo and in vitro. Baicalin treatment reversed the up‐regulation of Bax, cleaved‐caspase 3, cleaved‐caspase 9, and the down‐regulation of Bcl‐2. Meanwhile, Baicalin treatment alleviated Ang II‐induced increase of autophagosomes, restored autophagic flux, and down‐regulated LC3II, Beclin 1, as well as up‐regulated SQSTM1/p62 expression. Furthermore, autophagy inhibitor 3‐methyladenine treatment alleviated the increase of autophagosomes and the up‐regulation of Beclin 1, LC3II, Bax, cleaved‐caspase 3, cleaved‐caspase 9, down‐regulation of SQSTM1/p62 and Bcl‐2 expression after Ang II treated, which similar to co‐treatment with Baicalin. Baicalin treatment reduced the ratio of p‐AMPK/AMPK, while increased the ratio of p‐mTOR/mTOR. Baicalin alleviated Ang II‐induced cardiomyocyte apoptosis and autophagy, which might be related to the inhibition of the AMPK/mTOR pathway.