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.
Highlights
Cardiovascular diseases (CVDs) are among the leading causes of mortality and morbidity in type 2 diabetes patients worldwide [1]
These complications are traditionally associated with overt type 2 diabetes mellitus (T2DM), recent studies have shown that pre-diabetes is associated with augmented risk factors of developing CVDs
The results showed that the C-Reactive Protein (CRP) concentration of pre-diabetic control group (PC) was concentration of PC was significantly higher than of normal control (NC) (p < 0.05)
Summary
Cardiovascular diseases (CVDs) are among the leading causes of mortality and morbidity in type 2 diabetes patients worldwide [1]. More than half of type 2 diabetic patients suffer from cardiovascular diseases such as coronary heart disease, cardiac hypertrophy, atherosclerosis and hypertension [2,3]. These complications are traditionally associated with overt type 2 diabetes mellitus (T2DM), recent studies have shown that pre-diabetes is associated with augmented risk factors of developing CVDs. The CVD risk factors that are associated with pre-diabetes include insulin resistance, obesity, dyslipidaemia and oxidative stress [4]. Insulin resistance is directly linked with the development of cardiovascular complications such as increased blood pressure as a consequence of nitric oxide synthase inhibition and decreased nitric oxide (NO) bioavailability [5,6].
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