Hypolipidaemic and Insulin Secretagogue Activities of (R)-(−)-Carvone

Abstract

Background: Dyslipidaemias are common in patients with diabetes mellitus. A high prevalence of type 2 diabetes in hyperlipidaemic patients also exists. The aim of this study was to find a treatment that lowers both blood glucose and lipid levels simultaneously. Methods: The hypolipidaemic effect of (R)-(−)-carvone was investigated in a tyloxapol- induced hyperlipidaemia mice model. Furthermore, its effect on insulin secretion and proliferation of 1.1E7 human pancreatic β-cells was studied. In addition, using molecular docking, the binding affinity of (R)-(−)-carvone against 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG- CoA) reductase was estimated. Results: (R)-(−)-carvone (100 mg/kg) decreased plasma triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C) levels and atherogenic index by 90.6%, 49.3%, 56.6% and 70.3%, respectively, but it had no effect on high-density lipoprotein cholesterol (HDL-C). Furthermore, it increased hepatic triglyceride level and catalase activity by 79.6% and 59.6%, respectively. In-vitro, 500 μM (R)-(−)-carvone increased insulin secretion by 454.4% and proliferation of 1.1E7 cells with no cytotoxic effects up to a concentration of 100 μM. Molecular docking simulation demonstrated a good binding affinity with –5.03 Kcal/mol of (R)-(−)-carvone to HMG-CoA reductase. Conclusion: The hypolipidaemic effect of (R)-(−)-carvone is comparable to that of fenofibrate. (R)-(−)-carvone has the advantage over fenofibrate of not producing hypoglycaemia in animals. Furthermore, (R)-(−)-carvone increased proliferation and insulin secretion of human pancreatic β-cells.

Carvone Hypoglycemic and Hypolipidemic effects by regulation of key proteins involved in fatty acid beta-oxidation in alloxan-induced diabetic rats.

“…Following a one-month intervention with carvone, metformin, and atorvastatin, we saw a decrease in blood glucose levels. We also observed a decrease in lipid profile [25] in another study that showed that carvone has hypolipidaemic properties which come in the same line of our result . Plasma cholesterol levels and atherosclerosis have an undeniable causal link.…”

Molecular Mechanisms Underlying the Anti-Inflammatory Properties of (R)-(-)-Carvone: Potential Roles of JNK1, Nrf2 and NF-κB

“…The results obtained in this study suggest that (R)-(-)-carvone may be useful by targeting the interaction between inflammatory and anti-inflammatory/antioxidant signaling pathways and intermediates. Interestingly, some recent in vivo studies reported interesting activities of (R)-(-)-carvone, namely hypolipidaemic and insulin secretagogue activities [ 38 ], protection from doxorubicin-induced cardiotoxicity [ 39 ] and anti-allergic airway inflammation [ 40 ]. Although the molecular mechanisms underlying these activities were not clearly elucidated, the ability of (R)-(-)-carvone to activate Nrf2 and inhibit NF-κB may be especially relevant since all these conditions are associated with oxidative stress and inflammation.…”

“…Although the molecular mechanisms underlying these activities were not clearly elucidated, the ability of (R)-(-)-carvone to activate Nrf2 and inhibit NF-κB may be especially relevant since all these conditions are associated with oxidative stress and inflammation. In one of these studies, for instance, (R)-(-)-carvone decreased catalase activity in the liver of hyperlipidaemic mice [ 38 ]. Since catalase is an antioxidant enzyme whose expression is induced by Nrf2 [ 41 ], it can be speculated that activation of this transcription factor by (R)-(-)-carvone is a relevant mechanism underlying its beneficial effects in hyperlipidemic mice.…”

Bioactive properties of the aromatic molecules of spearmint (Mentha spicataL.) essential oil: a review

“…Several studies have described that carvone and carveol can produce a significant decrease in triglycerides (TG), total cholesterol (TC) and low-density lipoprotein (LDL) and a significant increase in high-density lipoprotein (HDL), suggesting anti-hyperlipidemic properties. 107,115 Furthermore, carvone decreased atherogenic index and increased proliferation and insulin secretion of human pancreatic β-cells.…”