Supplementation with a Cocoa–Carob Blend, Alone or in Combination with Metformin, Attenuates Diabetic Cardiomyopathy, Cardiac Oxidative Stress and Inflammation in Zucker Diabetic Rats

Abstract

Diabetic cardiomyopathy (DCM) is one of the main causes of mortality among diabetic patients, with oxidative stress and inflammation major contributors to its development. Dietary flavonoids show strong antioxidant and anti-inflammatory activities, although their potential additive outcomes in combination with antidiabetic drugs have been scarcely explored. The present study investigates the cardioprotective effects of a cocoa–carob blend (CCB) diet, rich in flavonoids, alone or in combination with metformin, in the development of DCM. Zucker diabetic fatty rats (ZDF) were fed with a CCB rich-diet or a control diet, with or without metformin for 12 weeks. Glucose homeostasis, cardiac structure and function, and oxidative and inflammatory biomarkers were analysed. CCB improved glucose homeostasis, and mitigated cardiac dysfunction, hypertrophy, and fibrosis in ZDF rats. Mechanistically, CCB counteracted oxidative stress in diabetic hearts by down-regulating NADPH oxidases, reducing reactive oxygen species (ROS) generation and modulating the sirtuin-1 (SIRT1)/ nuclear factor E2-related factor 2 (Nrf2) signalling pathway, overall improving antioxidant defence. Moreover, CCB suppressed inflammatory and fibrotic reactions by inhibiting nuclear factor kappa B (NFκB) and pro-inflammatory and pro-fibrotic cytokines. Noteworthy, several of these effects were further improved in combination with metformin. Our results demonstrate that CCB strongly prevents the cardiac remodelling and dysfunction observed in diabetic animals, highlighting its potential, alone or in adjuvant therapy, for treating DCM.

Novel Probiotic Lactic Acid Bacteria Were Identified from Healthy Infant Feces and Exhibited Anti-Inflammatory Capacities

“…Bacterial strains were incubated in MRS broth supplemented with different final concentrations (2,4,8,16,32,64,128,256, 512 and 1024 µg/mL) of antibiotics for 24 h incubation at 37 • C, and assayed in triplicate in a microplate reader (OD at 610 nm) [29]. MICs (minimum inhibitory concentrations) were considered the lowest concentrations of antibiotics that could inhibit strain growth, which was used to evaluate the antibiotic resistance of selected strains.…”

“…Oxidative stress is an excessive production of ROS, which can provoke the onset and progression of various diseases, including diabetes [ 16 ], cancer [ 17 ] and cardiovascular diseases [ 18 ], etc. Accumulating studies have suggested that intestinal flora metabolites may participate in the modulation of inflammation-related diseases through regulating oxidative stress [ 19 , 20 , 21 ].…”

Carob Antioxidants in Human Health: From Traditional Uses to Modern Pharmacology

“…Test group showed better biochemical test results, indicating possible potential of this powder in blood sugar control [42].…”

“…Antidiabetic activity of Carob was extensively studied [38][39][40][41][42], especially in the context of insulin-resistance and D-Pinitol activity, which is the major insulin regulator in Carob [129]. But Carob contains other natural products that have insulin regulation, as well as other health promoting activities: phytosterols (Figure 7) [91].…”

Role of Nutrients and Foods in Attenuation of Cardiac Remodeling through Oxidative Stress Pathways

“…The results showed attenuated cardiac dysfunction, hypertrophy, and fibrosis compared with the control group. The proposed mechanisms include the downregulation of NOX and modulation of the cellular antioxidant defense system, of which sirtuin-1 and Nrf2 are part [ 65 ].…”