Combinatory Effect and Modes of Action of Chrysin and Bone Marrow-Derived Mesenchymal Stem Cells on Streptozotocin/Nicotinamide-Induced Diabetic Rats

The purpose of this study was to see how chrysin and/or bone marrow-derived mesenchymal stem cells (BM-MSCs) affected streptozotocin (STZ)/nicotinamide (NA)-induced diabetic rats as an animal model of type 2 diabetes mellitus (T2DM). Male Wistar rats were given a single intraperitoneal (i.p.) injection of 60 mg STZ/kg bodyweight (bw) 15 min after an i.p. injection of NA (120 mg/kg bw) to induce T2DM. The diabetic rats were given chrysin orally at a dose of 100 mg/kg bw every other day, BM-MSCs intravenously at a dose of 1 × 10(6) cells/rat/week, and their combination for 30 days after diabetes induction. The rats in the diabetic group displayed impaired oral glucose tolerance and a decrease in liver glycogen content and in serum insulin, C-peptide, and IL-13 levels. They also had significantly upregulated activities in terms of liver glucose-6-phosphatase and glycogen phosphorylase and elevated levels of serum free fatty acids, IL-1β, and TNF-α. In addition, the diabetic rats exhibited a significant elevation in the adipose tissue resistin protein expression level and a significant decrease in the expression of adiponectin, insulin receptor-beta subunit, insulin receptor substrate-1, and insulin receptor substrate-2, which were associated with a decrease in the size of the pancreatic islets and in the number of β-cells and insulin granules in the islets. The treatment of diabetic rats with chrysin and/or BM-MSCs significantly improved the previously deteriorated alterations, with chrysin combined with BM-MSCs being the most effective. Based on these findings, it can be concluded that combining chrysin with BM-MSCs produced greater additive therapeutic value than using them separately in NA/STZ-induced T2DM rats.