Bredemolic Acid Improves Cardiovascular Function and Attenuates Endothelial Dysfunction in Diet-Induced Prediabetes: Effects on Selected Markers

Abstract

Prediabetes is an intermediate hyperglycaemic state which has been associated with cardiovascular dysfunction. However, cardiovascular dysfunction is not only caused by intermediate hyperglycaemia but also endothelial dysfunction, inflammation, and oxidative stress associated with prediabetes. Bredemolic acid (BA), an isomer of maslinic acid, has been reported to ameliorate the intermediate hyperglycaemia found in prediabetes; however, the effects of this triterpene on cardiovascular function have not yet been determined. Therefore, this study investigated the effects of BA on cardiovascular function in diet-induced prediabetic rats. Thirty-six male rats that weighed 150–180 g were divided into two groups, the non-prediabetic (n = 6) and the prediabetic groups (n = 30), which were fed normal diet (ND) and HFHC diet, respectively. The prediabetic rats were further subdivided into five groups (n = 6) and treated with either BA (80 mg/kg) or metformin (MET, 500 mg/kg) every third day for 12 weeks. After 12 weeks, blood samples and the heart were collected for biochemical analysis. The untreated prediabetic rats showed a significant increase in body mass index (BMI), waist circumference (WC), blood pressure, heart rate, lipid profile, lipid peroxidation, and inflammatory markers with significant decrease in endothelial function and antioxidant biomarkers by comparison with the non-prediabetic animals. The administration of BA significantly improved cardiovascular functions such as blood pressure, heart rate, and endothelial function. There was also a significant decrease in BMI, WC, lipid profile, lipid peroxidation, and inflammation with a concomitant increase in antioxidant capacity. BA administration improved cardiovascular function by attenuation of oxidative stress, inflammatory, and endothelial dysfunction markers.

Ameliorative Effects of Bredemolic Acid on Markers Associated with Renal Dysfunction in a Diet-Induced Prediabetic Rat Model

“…Administration of BA with or without diet modification has been shown in this study to attenuate renal dysfunction markers and urinary expression of podocin mRNA in the prediabetic state. These biological actions of BA may be due to the earlier reported combination of the improved insulin sensitivity, antihyperglycaemic and antioxidant properties of the pentacyclic triterpene (BA) [61,62]. Pentacyclic triterpenes have been reported as nontoxic antioxidants that have low pharmacokinetic activity of three days without side effects [28,29].…”

Assessing the risk factors for myocardial infarction in diet-induced prediabetes: myocardial tissue changes

“…These results are in accordance with the results reported by Su et al, in which subjects with diabetes and those with prediabetes had a significantly increased MDA concentration and a decreased SOD activity compared to subjects with standard glucose tolerance [ 58 ]. In the HFHC diet-induced prediabetes model, Akinnuga et al, reported a significant increase in MDA concentration in the prediabetes group compared to non-prediabetes [ 30 ].…”

“…The plasma was stored at – 80 °C in a Bio Ultra freezer (Snijders Scientific, Tilburg, Holland). The hearts of all the animals were excised, cut in half, rinsed with cold standard saline solution, weighed, and snapped frozen in liquid nitrogen before storage in Bio Ultra freezer at – 80 for biochemical analysis and in formalin for histological analysis [ 30 , 32 ].…”

“…FBG was determined using the tail-prick method and measured using a One-Touch select glucometer (Lifescan, Malta, United Kingdom). OGTT was conducted as per laboratory established protocol [27][28][29][30][31]. Briefly, after 12 h fasting period, FBG was measured (time, 0 min) in all the animals.…”

“…Aldose reductase, NADH oxidase 1 and Malondialdehyde (MDA) Aldose reductase and NADH oxidase 1 activity was measured in the heart tissue homogenate using their respective sandwich ELISA according to the manufacturer's protocol (Fine Biotech Co., Ltd., Wuhan, China). Lipid peroxidation was estimated by determining the concentration of MDA in the heart tissue homogenate according to a previously described protocol [30,33].…”