Plant-Derived Oleanolic Acid (OA) Ameliorates Risk Factors of Cardiovascular Diseases in a Diet-Induced Pre-Diabetic Rat Model: Effects on Selected Cardiovascular Risk Factors

Abstract

The pathogenesis of prediabetes is associated with risk factors such as chronic consumption of an unhealthy diet. Recent studies have reported that diet-induced pre-diabetes is also associated with risk factors of cardiovascular complications, hence this study was aimed at evaluating the effects of oleanolic acid (OA) on pre-diabetes rats. Pre-diabetes was induced by chronic exposure of Sprague Dawley rats (SD) to high-fat high-carbohydrate diet (20 weeks), whereas the non-pre-diabetes control (NC) was given standard rat chow. Pre-diabetes animals were grouped into five groups namely prediabetes control (PC), metformin treated (Met), metformin with diet intervention (Met + DI), oleanolic acid treated (OA), and oleanolic acid with diet intervention (OA + DI) then treated for 12 weeks. At the end of treatment, all animals were sacrificed where organs and tissues were harvested for biochemical analysis and histological studies. The results showed that PC had a significantly higher triglycerides (TGs), low density lipoprotein cholesterol (LDL-C, interleukin-6(IL-6), tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), mean arterial pressure (MAP) and hearts weights in comparison to NC (p < 0.05). However, the administration of OA, in both the presence and absence of dietary intervention showed a significant decrease in TGs, LDL-C, IL-6, TNFα, CRP, MAP, hearts weights (p < 0.05). In conclusion, the administration of OA was able to lower the risks of developing CVDs in pre-diabetes rat model through ameliorating dyslipidaemia, oxidative stress, hypertension, and low-grade inflammation. Therefore OA has the potential to be used as an alternative treatment to prevent the onset of CVDs during pre-diabetes stage even in the absence of dietary and lifestyle intervention.

<p>Plant-derived oleanolic acid ameliorates markers associated with non-alcoholic fatty liver disease in a diet-induced pre-diabetes rat model</p>

“…46,47 Moreover, OA has also been reported to reduce the risk of developing cardiovascular disease by lowering LDL-C particles while increasing high-density lipoprotein cholesterol (HDL-C) particles. 16,17 These findings correlated with the previous study that reported that derivatives of OA such as 3-acetyl-oleanolic acid have also been shown to lower intrahepatic total cholesterol (TC), TGs and macrovesicular steatosis in high-fat diet-fed rats. 16,18,48 While the observed decrease in plasma TGs and VLDLs may partly be attributed to dietary intervention, it may also be ascribed to the insulinsensitizing effects of OA.…”

“…17 This condition is characterized by complications including hypertriglyceridemia, insulin resistance and hyperinsulinemia which are risk factors for the development of NAFLD. 16,24 The conventional management of NAFLD involves the combination of insulin sensitizers and lifestyle modification therapy which include exercise and dietary modification. 25 However, pharmacological therapy is normally prescribed during T2DM while low patient compliance has been reported with regard to lifestyle modifications.…”

“…These findings may be attributed to the previously reported effects of OA which suggest that OA lowers caloric intake by restoring the coordination between ghrelin and leptin to regulate food intake and the resultant total body fat content. 16 Moreover, OA has been reported to improve insulin sensitivity in peripheral organs such as skeletal muscle and thus attenuate hyperglycemia in a pre-diabetic rat model. 17 This lowers the hepatic glucose influx which subsequently results in a decrease in hepatic lipogenesis.…”

“…17 This lowers the hepatic glucose influx which subsequently results in a decrease in hepatic lipogenesis. 16,32 However, OA + DI had more pronounced effects which may suggest that diet intervention may have also contributed in the reduction of liver weight and total body fat content. This may happen through minimizing the daily caloric intake which lowers the amount of energy that is stored in the form of fats, hence, a decrease in hepatic FFA influx.…”

“…Experimental pre-diabetes was induced in male Sprague-Dawley rats (n=36) using a previously described protocol. [16][17][18] The pre-diabetic animals were further sub-divided into six groups each group having six rats (n=6). The groups were as follows: pre-diabetic control group (PC) which were the prediabetic animals that continued with the experimental diet throughout the study period; metformin group (MET) which were the pre-diabetic animals that continued with the experimental diet but received metformin during treatment period; metformin and diet intervention group (MET + DI) which were the pre-diabetic animals that changed to a normal diet and received metformin during treatment period; oleanolic acid group (OA) which were the pre-diabetic animals that continued with experimental diet but received oleanolic acid during treatment period as well as OA and diet intervention group (OA + DI) which were the pre-diabetic animals that changed to a normal diet and received oleanolic acid during experimental period.…”