Hypoglycemic effects of dauricine, possibly through mitochondrial respiratory chain (complex I) and glycerol-3-phosphate dehydrogenase interaction pathways

Abstract

Two separate studies indicate that dauricine (DAU), an isoquinoline alkaloid derived from the Asian vine Menispermum dauricum, has shown anti-diabetic effects in laboratory animals. This study emphasizes evaluating the hypoglycemic effect against glucose-induced hyperglycemia animals in vivo along with possible molecular interventions of DAU through in silico studies. For this, adult male Swiss albino mice were treated with DAU (5 and 10 mg/kg) with or without the standard hypoglycemic drug metformin hydrochloride (MET) at 100 mg/kg via oral gavage and checked peripheral blood glucose levels (BGL) up to 3 hours from oral glucose administration (4 g/kg). The molecular docking study of DAU was conducted against MET-target proteins. Findings suggest that DAU dose-dependently and significantly (p < 0.05) decreased the BGL in animals from 60 minutes. At 180 minutes, it normalized BGL at both doses. With MET, it significantly (p < 0.05) and profoundly reduced the BGL compared to the individually treated groups. The molecular docking studies demonstrate that DAU has a strong binding affinity of –9.9 and −8.3 kcal/mol with the mitochondrial respiratory chain (complex I) receptor and mitochondrial glycerol-3-phosphate dehydrogenase receptor, respectively, whereas the standard drugs MET showed binding affinities between –4.9 and −4.3 kcal/mol for these subunits. Taken together, DAU dose-dependently reduced BGL and enhanced the hypoglycemic effect of MET in animals. We suppose that DAU may show its hypoglycemic effect on mice, possibly through mitochondrial respiratory chain (complex I) and glycerol-3-phosphate dehydrogenase receptor interaction pathways.