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The current study aimed to determine the antidiabetic and antidyslipidemic activities of moronic acid methyl ester (1) (compound 1 ) by in vivo, in vitro, in silico, and molecular biology studies. Compound 1 was evaluated to establish its dose-dependent antidiabetic and antihyperglycemic (50 mg/kg) activities, in diabetic and normoglycemic male CD1 mice, respectively. Also, compound 1 was subjected to a subacute study (50 mg/kg per day for 8 days) to determine blood biochemical profiles and the expression of protein tyrosine phosphatase 1B ( PTP-1B ), glucose transporter type 4 ( GLUT4 ), peroxisome proliferator-activated receptor α ( PPAR-α ), PPAR-γ , adiponectin, interleukin-1β (IL-1β), and monocyte chemoattractant protein 1 (MCP-1) in adipose tissue of animals after treatment. Different doses in acute administration of compound 1 decreased glycemia ( p  &lt; 0.05) compared with vehicle, showing greater effectiveness in the range 50-160 mg/kg. Also, the oral glucose tolerance test showed that compound 1 induced a significant antihyperglycemic action by opposing the hyperglycemic peak ( p  &lt; 0.05). Moreover, compound 1 subacute administration decreased glucose and triglyceride levels after treatment ( p  &lt; 0.05); while the expression of PPAR-α and PPAR-γ, adiponectin, and GLUT4 displayed an increase ( p  &lt; 0.05) compared with the diabetic control group. In conclusion, compound 1 showed antihyperglycemic, antidiabetic, and antidyslipidemic effects in normal and diabetic mice, probably due to insulin sensitization through increased mRNA expression of GLUT4 , PPAR-α , PPAR-γ , and adiponectin genes.

canadian journal of physiology and pharmacology

PPARα/γ, adiponectin, and GLUT4 overexpression induced by moronic acid methyl ester influenced glucose and triglyceride levels of experimental diabetic mice