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.

Esculeoside A Decreases Diabetic Cardiomyopathy in Streptozotocin-Treated Rats by Attenuating Oxidative Stress, Inflammation, Fibrosis, and Apoptosis: Impressive Role of Nrf2

“…In addition, the data of this study also confirmed inflammation in the LVs of these rats by the significant upregulation in the mRNA levels and nuclear levels of NF-κB and higher levels of ICAM-1, TNF-α, IL-6, and IL-1β. These data follow many other studies that have also shown similar results on the reduction in these antioxidant levels and in the elevation of MDA, TNF-α, IL-6, and collagen levels, as well as the of NF-κB in the hearts of STZ-diabetic rats [32,[50][51][52][53][54][55][56][57]. However, restoring all of these biochemical endpoints in the LVs of these rats was our strongest evidence that the cardioprotective effect of ESA is mediated by suppressing oxidative stress, inflammation, and fibrosis.…”

“…Also, intrinsic cell apoptosis is characterized by the reduced expression of anti-apoptotic genes (e.g., Bcl2), the overexpression of apoptotic genes such as Bax, damaged mitochondria, and increased mitochondrial cytochrome-c release, which ultimately activates caspase-3 and caspase-9, fragmenting the DNA [62]. Both extrinsic and intrinsic cell death modality was observed in the diabetic hearts of STZ-treated animals, as well as in the LV biopsies of patients with T1DM, and was attributed to oxidative damage [55,57,58,63]. Intrinsic cell apoptosis was also confirmed in the LVs of the STZ-diabetic animals in this study, as shown by their high cytoplasmic content of cytochrome-c, Bax, and caspase-3 and the lower levels of Bcl2.…”

Facile Double-Injection Strategy for the Engineering of Versatile Multiresponsive Hydrogels Encapsulating Drug-Loaded Micelles for Promoting Diabetic Wound Healing

“…AKBA is an active compound extracted from B. serrata with anti-inflammatory and antioxidant activity; however, its bioavailability is low due to its instability and poor solubility in water . The utilization can be improved by embedding it in an amphiphilic substance.…”

Mitochondrial dysfunction in the pathogenesis of hypertrophic cardiomyopathy

“…Нарушение передачи сигналов кальция в митохондриях обусловливает недостаток или избыток концентрации кальция в саркоплазме и нарушение сокращения кардиомиоцитов. Повышенный окислительный стресс также является признаком митохондриальной дисфункции, и мутации в генах, участвующих в механизмах антиоксидантной защиты, могут усугублять окислительное повреждение и способствовать развитию ГКМП [62,63]. В этот процесс могут быть вовлечены гены, кодирующие антиоксидантные ферменты супероксиддисмутазу или глутатионпероксидазу [64].…”