Nutrients (Mar 2023)
The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK
Abstract
This study examined the protective effect of 11-keto-β-boswellic acid (AKBA) against streptozotocin (STZ)-induced diabetic cardiomyopathy (DC) in rats and examined the possible mechanisms of action. Male rats were divided into 5 groups (n = 8/each): (1) control, AKBA (10 mg/kg, orally), STZ (65 mg/kg, i.p.), STZ + AKBA (10 mg/kg, orally), and STZ + AKBA + compound C (CC/an AMPK inhibitor, 0.2 mg/kg, i.p.). AKBA improved the structure and the systolic and diastolic functions of the left ventricles (LVs) of STZ rats. It also attenuated the increase in plasma glucose, plasma insulin, and serum and hepatic levels of triglycerides (TGs), cholesterol (CHOL), and free fatty acids (FFAs) in these diabetic rats. AKBA stimulated the ventricular activities of phosphofructokinase (PFK), pyruvate dehydrogenase (PDH), and acetyl CoA carboxylase (ACC); increased levels of malonyl CoA; and reduced levels of carnitine palmitoyltransferase I (CPT1), indicating improvement in glucose and FA oxidation. It also reduced levels of malondialdehyde (MDA); increased mitochondria efficiency and ATP production; stimulated mRNA, total, and nuclear levels of Nrf2; increased levels of glutathione (GSH), heme oxygenase (HO-1), superoxide dismutase (SOD), and catalase (CAT); but reduced the expression and nuclear translocation of NF-κB and levels of tumor-necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These effects were concomitant with increased activities of AMPK in the LVs of the control and STZ-diabetic rats. Treatment with CC abolished all these protective effects of AKBA. In conclusion, AKBA protects against DC in rats, mainly by activating the AMPK-dependent control of insulin release, cardiac metabolism, and antioxidant and anti-inflammatory effects.
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