Chrysanthemum Morifolium Extract Improves Renovascular Hypertension-induced Cardiac Hypertrophy And Its Possible Mechanisms In Rats

Aim: To examine the effect of Chrysanthemum morifolium extract(CME) on renovascular hypertension-induced cardiac hypertrophy in rats andinvestigate the potential mechanisms.Methods: The rat model of cardiac hypertrophy was established by two-kidneyone-clip method, followed by oral administration of CME 75 and 150 mg/kg for 4 weeks. In vitro experiment, H9c2 cells were cultured under the stimulus of angiotensinⅡ(AngⅡ) and hypoxia to establish the hypertrophiccellmodel. The animal blood pressure, heart weight index, serum AngⅡ, blood glucose,serum and myocardial free fatty acids(FFA), myocardial superoxide dismutase(SOD), glutathione reductase(GR), glutathione-s-transferase(GST), glutathione peroxidase(GSH-Px) and malondialdehyde(MDA) contents were measured. Histological changes in myocardial tissue were examined under a light microscope. The total protein, atrial natriuretic peptide(ANP) and FFA levels in the cultured cells as well asglucose and FFA in the cultured supernatants were determined. The protein expressions of hypoxia inducible factor-1α(HIF-1α), peroxisome proliferator-activated receptor α/γ(PPARα/γ), camitine palmitoyltmnsferase-1A(CPT-1A), glycerol 3 phosphate acyltransferase(GPAT), glucose transporter-4(GLUT-4), pyruvate dehydrogenase kinase-4(PDK-4), nuclear factor(NF-κB) and transforming growth factor β1(TGF-β1) in myocardial tissues and cultured cells were determined by Western Blot method.Results:After treatment of cardiac hypertrophied rats with CME for 4 weeks, the blood pressure, heart weight index, serum AngⅡ,myocardial MDA, serum and myocardial FFA levels were lowered, especially in the CME 150 mg/kg group(P<0.05 or P<0.01), while the bloodglucose, myocardial SOD, GR, GST and GSH-Px contents were obviously increased(P<0.05 or P<0.01). The histological evaluation demonstrated that CME treatment could decrease the myocardialcross-sectional area. The Western Blot results showed that CME could significantly down-regulate the expressions of HIF-1α, PPARγ, GPAT, GLUT-4, NF-κB and TGF-β1 proteins in hypertrophic myocardial tissues(P<0.05 or P<0.01), and up-regulate the expressions of PPARα, CPT-1A and PDK-4 proteins in hypertrophic myocardial tissues(P<0.05 or P<0.01). In vitro, the luteolin and chlorogenic acid-treated H9c2 cells showed that the FFA level in cultured cells and supernatants, total protein and ANP levels in cultured cells were lowered(P<0.05 or P<0.01), whereas the glucose content in the cultured supernatants was increased(P<0.05 or P<0.01). The Western Blot results showed that luteolin and chlorogenic acid could significantly down-regulate the expressions of HIF-1α, PPARγ, GPAT and GLUT-4 proteins(P<0.05 or P<0.01), and up-regulate the expressions of PPARα, CPT-1A and PDK-4 proteins inthe cultured cells(P<0.05 or P<0.01).Conclusion:Chrysanthemum morifolium extract might improve renovascular hypertension-induced cardiac hypertrophy in rats, and its mechanisms might be related to the correction of abnormal cardiac glucose and lipid metabolism via regulating HIF-1α-PPARα/γ-mediatedsignalling pathway and increment of cardiac antioxidant ability.