Syzygium aromaticum bud (clove) essential oil is a novel and safe aldose reductase inhibitor: in silico, in vitro, and in vivo evidence.

PURPOSE: This study aimed to evaluate the antioxidant and antidiabetic properties of clove essential oil (CEO) and to elucidate its mode of action, using selected biochemical targets, relevant to diabetes, and, specifically, its inhibitory effect on the polyol pathway. METHODS: In the current study, CEO was examined for its inhibitory effects on aldose reductase in silico, in vitro, and in vivo, as well as its antioxidative activity. RESULTS: In silico docking studies showed that all the selected major compounds of CEO have an energy change ranging between - 5.5 and - 8.8 kcal/mol and an inhibition constant ranging between 357.08 nM and 93.12 µM. CEO significantly inhibits aldose reductase with an IC50 value of 58.55 ± 5.84 µg/mL in a noncompetitive manner. The supplementation of CEO at 20 mg/kg BW decreases retinal sorbitol dehydrogenase activity via decreased aldose reductase activity in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. Moreover, diabetic rats injected with CEO have exhibited improved levels of glycemia. The IC50 values for ABTS, hydroxyl, and hydrogen peroxide scavenging activities of CEO were found to be 34.42, 277.4, and 39.99 µg/mL, respectively. Reducing power assay and phosphomolybdate assay exhibited a reduction force with the A0.5 values of 50.25 and 140.16 µg/mL, respectively. CONCLUSION: CEO potentially exerts a beneficial effect on diabetes-related complications due to its antioxidant and inhibitory effect on aldose reductase activity.