Anti-inflammatory Effect of Ursolic Acid on Male Wistar Rats with High-carbohydrate High-fat Diet-induced Metabolic Syndrome

Résumé

Background: Metabolic syndrome (MS) comprises a cluster of cardiometabolic risk factors. The presence of these risk factors predisposes an individual to other medical complications. Increased cellular inflammation produces increased levels of biomarkers that are correlated with both insulin resistance and low-grade inflammation, leading to the progression of MS and increased risk for diabetes and CVD. This study investigated the mechanism by which ursolic acid (UA) exerts its anti-inflammatory effect in HCHFD-induced MS in male Wistar rats. Method: Twenty male Wistar rats were randomly divided into 4 groups (n =5) and fed daily for 20 weeks. Group I received normal diet (ND) and distilled water (DW); group II received ND and UA; group III received HCHFD and DW; group IV received HCHFD and UA. The HCHFD was formulated in-house and the drinking water was augmented with 20% fructose. A dose of 250 mg/kg body weight of UA was administered orally to UA-treated groups starting 12 weeks after initiation of the HCHFD for a further 8 weeks. Body mass index (BMI) was measured. Blood samples were obtained for serum insulin, lipid profile, TNF-α, IL-6 and adiponectin assessment. Adipose tissue PPAR-γ mRNA was evaluated using real-time polymerase chain reaction technique. Histology of liver and adipose tissue was performed. All significant results were reported at P<0.05. Results: The percentage increase in BMI was lower in the HCHFD+UA-fed animals compared to the HCHFD+DW-fed animals. In the HCHFD+UA-fed animals, serum insulin, cholesterol, triglyceride and LDL-C decreased while HDL-C increased compared to the HCHFD+DW-fed animals respectively. The HCHFD+UA group had decreased serum TNF-α and IL-6 and increased adiponectin level compared to the HCHFD+DW-fed animals. Adipose tissue PPAR-γ mRNA level was upregulated in the HCHFD+UA animals compared to HCHFD+DW group. The architecture of the liver parenchyma was restored to near normal by UA. Conclusion: UA has anti-inflammatory effect on male Wistar rats with HCHFD-induced MS by decreasing serum TNF-α and IL-6, increasing adiponectin and upregulating adipose tissue PPAR-γ mRNA levels, respectively.