Verbenone and L-arginine from Daucus carota Seeds Attenuate Oxidative Stress in Streptozotocin-Nicotinamide (STZ-NAD)-Induced Diabetic Mice: Evidence from In vitro and In vivo Studies

Free radicals are produced in diabetes mellitus (DM), due to protein glycosylation and glucose autooxidation. However, compounds from plants were proven to be effective in the management of DM and related conditions. This study evaluated the antioxidant effect of verbenone, L-arginine, and their ratio combinations in diabetic mice. DM was induced in mice by intraperitoneal (IP) injection of streptozotocin and nicotinamide adenine dinucleotide (NAD) and the diabetic mice were treated with verbenone, L-arginine, and their ratios for 28 days. In the in vitro study, L-arginine expressed higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, while verbenone and L-arginine expressed higher nitric oxide (NO) and hydrogen peroxide (H2O2) scavenging activities, especially at higher concentrations when compared with vitamin C. At the end of the treatment period, the levels of blood glucose, total protein, and malondialdehyde were significantly increased while the levels of reduced glutathione, nitrite, and activities of glutathione peroxidase, glutathione transferase, catalase, superoxide dismutase were significantly decreased in the diabetic untreated mice. However, these diabetes-induced alterations were reversed to normal levels after the administration of verbenone, L-arginine, and their ratio combinations at 100 and 200 mg/kg body weight. Furthermore, in silico studies revealed the antioxidant potential of both verbenone and L-arginine by their interaction with antioxidant proteins, expressing their potential antioxidant properties. The results of the study indicated that verbenone, L-arginine, and their ratio combination possess antioxidant property and attenuate oxidative stress in diabetic mice. HighlightsO_LIVerbenone and L-arginine are natural compounds found in Daucus carota seeds and other plants. C_LIO_LIVerbenone and L-arginine possess in vitro and in vivo antioxidant activities. C_LIO_LIVerbenone, L-arginine and their ratio combination (1:1) enhance the activities of antioxidant enzymes in streptozotocin-nicotinamide (NAD-STZ) induced diabetic mice. C_LIO_LIFurthermore, the two compounds interacted with antioxidant proteins, expressing their potential antioxidant property in an in silico model. C_LI