Aqueous Extract of Alstonia boonei Bark Reduces Chronic Hyperglycemia and Prevents its Complications through Increase of Hepatic Global Dna Methylation in Diabetic Wistar Rats

Abstract

Aim:  DNA methylation profile is involved in several physiological processes. Its alterations in the liver of diabetic patients characterized by global hypomethylation are associated with the pathophysiology of type 2 diabetes and its complications. The present study has evaluated the effect of the aqueous extract of Alstonia boonei barks on the global methylation of hepatic DNA in association with hyperglycemia and diabetes complications induced by high-fat diet (HFD) feeding and administering of streptozotocin (STZ) which mimics the metabolic abnormalities very similar to those seen in human Type 2 diabetes. Methods: A. boonei barks were harvested, processed, dried, ground and an aqueous extraction was prepared (ratio 1/10 w/v). An in vivo study was conducted in an animal model of high-fat-streptozotocin (HF-STZ) induced diabetes. Rats were divided into five groups of five rats each: a normoglycemic group, an untreated hyperglycemic group, three hyperglycemic groups including two test groups receiving aqueous extract of A. boonei barks (AEAB) by esophageal gavage at the doses of 200 and 400 mg/kg body weight once daily and a reference group receiving metformin at 10 mg/kg body weight. After 28 days of experimentation during which fasting blood glucose levels were taken every 14 days under fasting conditions, the animals were sacrificed. Plasma and liver homogenate samples from the sacrificed rats were used for biochemical assays (markers of oxidative stress such as malondialdehyde level, superoxide dismutase (SOD) and catalase activity, and markers of lipid profile such as total cholesterol, and triglycerides, HDL-c, LDL-c and VLDL-c).  The analysis of the global DNA methylation profile was performed by the immunoprecipitation. Pearson's correlation was used to evaluate the relationship between the values. Results: The aqueous extract increased the hepatic DNA methylation by 0.41% and 0.63% at 200 and 400 mg/kg body weight, respectively, compared to metformin (0.47%±0, 05). This effect was significantly associated with the hypoglycemic effect obtained at 400 mg/kg body weight with a decrease in initial blood glucose level of -29.87%. Conclusion: AEAB reduces chronic hyperglycemia and prevents its complications by increasing global hepatic DNA methylation.