Computational and Pharmacological Evaluation of Carveol for Antidiabetic Potential

Abstract

Background: Carveol is a natural drug product present in the essential oils of orange peel, dill, and caraway seeds. The seed oil of Carum Carvi has been reported to be antioxidant, anti-inflammatory, anti-hyperlipidemic, antidiabetic, and hepatoprotective. Methods: The antidiabetic potential of carveol was investigated by employing in-vitro, invivo, and in-silico approaches. Moreover, alpha-amylase inhibitory assay and an alloxaninduced diabetes model were used for in-vitro and in-vivo analysis, respectively. Results: Carveol showed its maximum energy values (≥-7 Kcal/mol) against sodiumglucose co-transporter, aldose reductase, and sucrose-isomaltase intestinal, whereas it exhibited intermediate energy values (≥-6 Kcal/mol) against C-alpha glucosidase, glycogen synthase kinases-3b, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and other targets according to in-silico analysis. Similarly, carveol showed lower energy values (≥ 6.4 Kcal/mol) against phosphoenolpyruvate carboxykinase and glycogen synthase kinase-3b. The in-vitro assay demonstrated that carveol inhibits alpha-amylase activity concentration-dependently. Carveol attenuated the in-vivo alloxan-induced (1055.8 µMol/Kg) blood glucose level in a dose-and timedependent manner (days 1, 3, 6, 9, and 12), compared to the diabetic control group, and further, these results are comparable with the metformin positive control group. Carveol at 394.1 µMol/Kg improved oral glucose tolerance overload in rats compared to the hyperglycemic diabetic control group. Moreover, carveol also attenuated the glycosylated hemoglobin level along with mediating anti-hyperlipidemic and hepatoprotective effects in alloxan-induced diabetic animals. Conclusions: This study reveals that carveol exhibited binding affinity against different targets involved in diabetes and has antidiabetic, anti-hyperlipidemic, and hepatoprotective actions.

Carveol Promotes Nrf2 Contribution in Depressive Disorders through an Anti-inflammatory Mechanism

“…In line with these studies, natural moieties based on their rich antioxidant potential are frequently investigated as these drugs have therapeutic potential against many stress mediators, including inflammatory factors and free radical species [ 44 ]. Carveol, essential oil has previously demonstrated antidiabetic potential possibly by attenuating oxidative stress [ 45 ]. Furthermore, carveol has shown neuroprotective potential in the ischemic brain injury model by ameliorating the infarction area by promoting the Nrf2 pathway [ 33 ].…”

Carveol Attenuates Seizure Severity and Neuroinflammation in Pentylenetetrazole‐Kindled Epileptic Rats by Regulating the Nrf2 Signaling Pathway

“…In another study, carveol mitigated hepatocellular necrosis by showing antioxidant, antihyperlipidemic, and anti-inflammatory activities [ 41 ]. Furthermore, carveol exhibited promising results in the management of diabetes [ 42 ]. Given the strong antioxidant potential of carveol and its promising properties, this study is aimed at evaluating whether carveol administration can ameliorate PTZ-induced epileptogenesis in a rat model by modulating the Nrf2 pathway.…”

In Vitro Evaluation of the Anti-Diabetic Potential of Aqueous Acetone Helichrysum petiolare Extract (AAHPE) with Molecular Docking Relevance in Diabetes Mellitus

“…Our docking analysis suggests that most of the bioactive compounds in AAHPE could compete with the substrate for the enzyme’s active site in a similar manner as acarbose does [ 61 , 62 , 63 ]. Acarbose has been reported in the literature to be a competitive inhibitor of α-amylase and α-glucosidase [ 62 , 64 , 65 ].…”