Shatoor Abdullah S, Al Humayed Suliman, Almohiy Hussain M
Department of Medicine, Cardiology Section, College of Medicine, King Khalid University (KKU), Abha, Saudi Arabia.
Department of Internal Medicine, College of Medicine, King Khalid University (KKU), Abha, Saudi Arabia.
Saudi J Biol Sci. 2021 Mar;28(3):1966-1977. doi: 10.1016/j.sjbs.2020.12.052. Epub 2021 Jan 6.
This study evaluated the effect of 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 aqueous extract (200 mg/kg) for 7 days, daily. Fasting plasma glucose and insulin levels were not significantly changed in -treated rats but were significantly reduced after both the intraperitoneal glucose or insulin tolerance tests. Besides, 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, aqueous extract boosted insulin signaling in the LV of rats by increasing the protein levels of p-IRS (Tyr) and p-Akt (Ser) and suppressing protein levels of p-mTOR (Ser 2448) and p-IRS (Ser). In parallel, 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), a major energy modulator that stimulates glucose utilization. In conclusion, short-term administration of C. aqueous extract shifts the cardiac metabolism toward glucose utilization, thus making this plant a potential therapeutic medication in cardiac disorders with impaired metabolism.
本研究评估了水提取物对成年雄性健康Wistar大鼠心脏底物利用和胰岛素信号传导的影响。大鼠(每组n = 18)每日给予生理盐水(赋形剂)或用水提取物(200 mg/kg)处理7天。处理后的大鼠空腹血糖和胰岛素水平无显著变化,但在腹腔注射葡萄糖或胰岛素耐量试验后显著降低。此外,水提取物分别显著增加了磷酸果糖激酶(PFK)和丙酮酸脱氢酶(PDH)的左心室(LV)活性,这两种酶分别是糖酵解和葡萄糖氧化的标志物,并抑制了丙酮酸脱氢酶激酶4(PDK4)的水平,PDK4是PDH的抑制剂。同时,它显著降低了肉碱棕榈酰转移酶1(CPT1)和PPARα的LV水平,这两种酶是脂肪酸(FAs)氧化的标志物。在基础和胰岛素刺激下,水提取物通过增加p-IRS(Tyr)和p-Akt(Ser)的蛋白水平并抑制p-mTOR(Ser 2448)和p-IRS(Ser)的蛋白水平,增强了大鼠LV中的胰岛素信号传导。同时,水提取物还增加了处理后LV膜部分中GLUT-4的蛋白水平。所有这些作用还与AMPK活性(Thr磷酸化)的显著增加有关,AMPK是一种刺激葡萄糖利用的主要能量调节剂。总之,短期给予水提取物可使心脏代谢转向葡萄糖利用,因此使这种植物成为代谢受损的心脏疾病的潜在治疗药物。