Myricetin May Improve Cardiac Dysfunction Possibly Through Regulating Blood Pressure and Cellular Stress Molecules in High-Fructose-Fed Rats

Background: The aim of this study was to examine the effect of myricetin on cardiac dys- function caused by high fructose intake. Methods: Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Myricetin was administered by oral gavage for the last 6 weeks. Systolic blood pressure was measured by tail -cuff method. The effects of isoprenaline, phenylephrine, and ace- tylcholine on cardiac contractility and rhythmicity were recorded in the isolated right atrium and left ventricular papillary muscles. In addition to biochemical measurements, the cardiac expressions of cellular stress -related proteins were determined by western blotting. Results: Myricetin improved systolic blood pressure but did not affect body weight, plasma glucose, and triglyceride levels in fructose -fed rats. The impairment of isoprenaline- and phenylephrine-mediated increases in atrial contraction and sinus rate in fructose -fed rats was restored by myricetin treatment. Isoprenaline, phenylephrine, and acetylcho- line -mediated papillary muscle contractions were not changed by fructose or myricetin administration. The expression of the mitochondrial fission marker dynamin-related protein 1 and the mitophagic marker PTEN-induced kinase 1 (PINK1) was enhanced in the fructose -fed rat, and myricetin treatment markedly attenuated PINK1 expression. Highfructose intake augmented phosphorylation of the proinflammatory molecule Nuclear factor kappa B (NF-kappa B) and the stress -regulated kinase JNK1, but myricetin only reduced NF-kappa B expression. Moreover, myricetin diminished the elevation in the expression of the pro-apoptotic Bax. Conclusion: Our results imply that myricetin has a protective role in cardiac irregulari- ties induced by a high -fructose diet through reducing systolic blood pressure, improving cardiac adrenergic responses, suppressing PINK1, NF-kappa B, and Bax expression, and thus reflecting a potential therapeutic value.