Antidiabetic potential of Chromolaena Odorata leave extract and its effect on Nrf2/keap1 antioxidant pathway in the liver of diabetic-induced Wistar Rats

The incidence of liver dysfunction increases in diabetes due to insulin resistance and oxidative stress. Chromolaena odorata is a dominant medicinal plant used in traditional medicine as a remedy for many diseases, particularly diabetes mellitus but the underlying mechanism of the plants chemicals is yet to be documented. This study investigated possible mechanisms behind the folkloric use of C. odorata in the management of diabetes. The effect of this plant on genes linked with glucose metabolism and oxidative stress was investigated in the liver of diabetic rats. The rats were divided into diabetes control, normal control, C. odorata extract (200 mg/kg) and diabetic + C. odorata extract (200 gm/kg). Diabetes was induced in the rats by intraperitoneal injection of a buffered solution of STZ (65 mg/kg). Ethanolic extract of C. odorata leaves (200 mg/kg) was orally administered to the treatment groups for a period of three weeks. The mRNA expression of Glut2, glucokinase, Nrf2 and keap1 were quantified using RT-PCR. Molecular docking studies were further explored to denote compounds from C. odorata that might be responsible for its liver protective effect in diabetes. In the diabetic group, liver mRNA expressions of Glut2, glucokinase and Nrf2 were down-regulated (p < 0.05) while the expression of keap1 was upregulated (p < 0.05), relative to the control group. The treatment of diabetic rats with ethanolic extract of C. odorata leaves (200 mg/kg), however, upregulated the mRNA expression of Glut2, glucokinase and Nrf2 while repressing keap1 mRNA expression. Docking results showed that 5,7-dihydroxy-6-4-dimethoxyflavanone and luteolin as possible compounds from C. odorata potentiating this protective role. These findings suggest that C. odorata could mitigate liver dysfunction induced by diabetes.