Plant-derived oleanolic acid ameliorates markers of subclinical inflammation and innate immunity activation in diet-induced pre-diabetic rats

Abstract

Aims: Sub-clinical inflammation during pre-diabetes is one of the predisposing factors that facilitates the progression of pre-diabetes to type 2 diabetes. The administration of oleanolic acid (OA) with or without dietary intervention ameliorates the metabolic and cardiovascular complications in diet-induced pre-diabetes animal models of pre-diabetes. This study aimed to investigate whether OA can also suppress immune activation and ameliorate pro-inflammatory markers. Methods: Pre-diabetes was induced by feeding Sprague Dawley rats a high-fat high carbohydrate diet for 20 weeks. The pre-diabetic rats were then treated with OA (80 mg/kg) or metformin (500 mg/kg) in the presence or absence of dietary interventions for a period of 12 weeks. At the end of the treatment period, the animals were euthanised and whole blood was used for platelet and immune cell count while plasma was used for fibrinogen, cluster differentiation 40 ligand and pro-inflammatory cytokine evaluation. Results: The results of this study revealed that OA, with or without dietary intervention, improved lipid metabolism by restoring high-density lipoprotein (HDL) and low-density lipoproteins (LDLs) as well as reducing platelets and immune cell counts. Furthermore, OA also decreased plasma proinflammatory cytokines, including tumour necrosis factor-α and -1β. Markers of immune activation such as C-reactive protein, fibrinogen, and CD40L were also decreased upon administration of OA with or without dietary intervention. Conclusion: The findings of this study suggest that OA may provide an alternative to prevent the progression of pre-diabetes to overt diabetes. This was evident by the reduction of differential white blood cell count and proinflammatory cytokines that exercebate insulin resistance. However, more studies are needed to elucidate the molecular mechanisms and to improve efficacy.

Oleanolic Acid: Extraction, Characterization and Biological Activity

“…The intake of the triterpenoid-rich oil improved both the oral glucose (GTT) and insulin tolerance tests (ITT). In fact, OA has been shown to coadjuvant metformin to ameliorate the consequences of pre-diabetes in Sprague–Dawley rats a high-fat high carbohydrate diet for 20 weeks [ 153 ]. According to these authors OA improved lipid metabolism, decreased plasma proinflammatory cytokines, as wells as C-reactive protein, fibrinogen and CD40L in the animals.…”

“…Obese mice fed a high-fructose diet presented increased RNA expression of TNFα and MCP-1 in white adipose tissue and liver, which was ameliorated after being fed pomace olive oil rich in tritepenes, including OA [ 96 , 152 , 161 ]. In addition, Gamede et al [ 153 ] found decreased plasma proinflammatory cytokines, including TNF-α and IL-1β in Sprague Dawley rats fed a high fat, high carbohydrate diet after a 20-week treatment with OA.…”

Diet‐induced prediabetes: Effects on the activity of the renin–angiotensin–aldosterone system in selected organs

“…The Animal Research Ethics Committee at the University of KwaZulu‐Natal (ETHICS#: AREC/086/018D) approved all animal experiments. Before being exposed to the experimental diets, the animals were permitted to acclimate to their new habitat for 1 week while eating standard rat chow and drinking tap water 21 . Procedures involving animal care were carried out in accordance with the institutional guidelines for animal care of the University of KwaZulu‐Natal, which adhere to the principles and guidelines of the Canadian Council on Animal Care.…”

“…At the end of the trial, all animals were anesthetized for 3 min with isoflurane (100 mg/kg; Safeline Pharmaceuticals Pty Ltd, Roodeport, South Africa) administered in a gas anesthetic chamber (Biomedical Resource Unit, UKZN, Durban, South Africa) 21 . Blood was obtained from unconscious rats through heart puncture and then injected into separate pre‐cooled heparinized containers.…”

Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part I)

“…The inhibitory activity of OA on pro-inflammatory cytokines may ameliorate the progression of pre-diabetes state into type 2 diabetes by diminishing subclinical inflammation. OA significantly reduces the expression of TNF-α, IL-1β, NF-kB, and CD40L in pre-diabetic animals; CD40L is an inflammatory mediator belonging to the TNF family that interacts with immune cells such as T cells and induces the production of chemokines, leading to inflammatory responses [ 155 ]. A frequent complication of diabetes is the increased incidence of chronic kidney disease; Gamede et al have continued their research by assessing the alleviating effect of OA on kidney-affected pre-diabetic rats.…”