Short-term administration of C. aronia stimulates insulin signaling, suppresses fatty acids metabolism, and increases glucose uptake and utilization in the hearts of healthy rats

This study evaluated the effect of Crataegus aronia (C. aronia) aqueous extract on cardiac substrate utilization and insulin signaling in adult male healthy Wistar rats. Rats (n = 18/group) were either administered normal saline (vehicle) or treated with C. aronia aqueous extract (200 mg/kg) for 7 days, daily. Fasting plasma glucose and insulin levels were not significantly changed in C. aronia-treated rats but were significantly reduced after both the intraperitoneal glucose or insulin tolerance tests. Besides, C. aronia significantly increased the left ventricular (LV) activities of phosphofructokinase (PFK) and pyruvate dehydrogenase (PDH), two markers of glycolysis and glucose oxidation, respectively, and suppressed the levels of pyruvate dehydrogenase kinase 4 (PDK4), an inhibitor of PDH. Concomitantly, it significantly reduced the LV levels of carnitine palmitoyltransferase 1 (CPT1) and PPARα, two markers of fatty acid (FAs) oxidations. Under basal and insulin stimulation, C. aronia aqueous extract boosted insulin signaling in the LV of rats by increasing the protein levels of p-IRS (Tyr(612)) and p-Akt (Ser(473)) and suppressing protein levels of p-mTOR (Ser 2448) and p-IRS (Ser(307)). In parallel, C. aronia also increased the protein levels of GLUT-4 in the membrane fraction of the treated LVs. All these effects were also associated with a significant increase in AMPK activity (phosphorylation at Thr(172)), a major energy modulator that stimulates glucose utilization. In conclusion, short-term administration of C. aronia aqueous extract shifts the cardiac metabolism toward glucose utilization, thus making this plant a potential therapeutic medication in cardiac disorders with impaired metabolism.