Abstract
Bawei Chenxiang Wan (BCW), a well-known traditional Chinese Tibetan medicine formula, is effective for the treatment of acute and chronic cardiovascular diseases. In the present study, we investigated the effect of BCW in cardiac hypertrophy and underlying mechanisms. The dose of 0.2, 0.4, and 0.8 g/kg BCW treated cardiac hypertrophy in SD rat model induced by isoprenaline (ISO). Our results showed that BCW (0.4 g/kg) could repress cardiac hypertrophy, indicated by macro morphology, heart weight to body weight ratio (HW/BW), left ventricle heart weight to body weight ratio (LVW/BW), hypertrophy markers, heart function, pathological structure, cross-sectional area (CSA) of myocardial cells, and the myocardial enzymes. Furthermore, we declared the mechanism of BCW anti-hypertrophy effect was associated with activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator–activated receptor-α (PPAR-α) signals, which regulate carnitine palmitoyltransferase1β (CPT-1β) and glucose transport-4 (GLUT-4) to ameliorate glycolipid metabolism. Moreover, BCW also elevated mitochondrial DNA-encoded genes of NADH dehydrogenase subunit 1(ND1), cytochrome b (Cytb), and mitochondrially encoded cytochrome coxidase I (mt-co1) expression, which was associated with mitochondria function and oxidative phosphorylation. Subsequently, knocking down AMPK by siRNA significantly can reverse the anti-hypertrophy effect of BCW indicated by hypertrophy markers and cell surface of cardiomyocytes. In conclusion, BCW prevents ISO-induced cardiomyocyte hypertrophy by activating AMPK/PPAR-α to alleviate the disturbance in energy metabolism. Therefore, BCW can be used as an alternative drug for the treatment of cardiac hypertrophy.
Highlights
Cardiac hypertrophy is initially regarded as a compensatory response of the heart to various physiological or pathological stimuli
Our observations revealed that 10 μM ISO administered for 24 h significantly increased the mRNA levels of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and β -MHC in the neonatal rat cardiomyocytes (NRCMs) (Figure 8H), and similar results were observed in the cell surface of cardiomyocytes
This study revealed the protection of Bawei Chenxiang wan (BCW) on ISO-induced cardiac hypertrophy in vivo and in vitro, as showed by improved heart function, macro and micromorphology, and cardiac hypertrophy markers, which were associated with improving the energy metabolism by activating the AMPK/ PPAR-α signaling pathway
Summary
Cardiac hypertrophy is initially regarded as a compensatory response of the heart to various physiological or pathological stimuli. Cardiac hypertrophy is known to occur due to oxidative stress, inflammation, and autophagy, the main cause has not been elucidated (Li et al, 2016; Anthony et al, 2019; Geng et al, 2019). A number of studies report that metabolic dysfunction is a hallmark of cardiac hypertrophy and heart failure (Tian et al, 2018; Dhyani et al, 2019). Previous findings in our laboratory and others have proved that the cardiac hypertrophy is characterized by a metabolic switch in the utilization of energy source that uses glucose as an energy source rather than utilizing fatty acid (Ingwall, 2009; Zou et al, 2013; Gao et al, 2015; Yue et al, 2016). The energy metabolism can contribute to contractile dysfunction and the progressive left ventricular remodeling that are characteristics of the heart failure state (Stanley et al, 2005; Luptak et al, 2018)
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