NRF2 activation by myrcene restores redox balance and metabolic homeostasis in a mouse model of type 2 diabetes.

Abstract

UNLABELLED: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterised by impaired insulin signalling, chronic hyperglycaemia, and associated metabolic dysfunction. Plant-derived bioactive compounds are increasingly explored as potential therapeutic agents for its management. To investigate the anti-diabetic effect and underlying mechanism of Myrcene, in streptozotocin (STZ) + high-fat diet (HFD) induced diabetes in mice, male C57BL/6 mice were administered HFD for eight consecutive weeks, followed by low-dose STZ injections (60 mg/kg) during the succeeding week to develop diabetes. After diabetes was established, the mice received a daily oral dose of Myrcene (50 mg/kg) for 15 days. The research evaluated changes in physiological parameters, blood biomarkers (such as glucose, lipoprotein, etc.), and tissue structure. Furthermore, molecular docking and western blot analyses were performed to examine the expression of oxidative stress markers regulated by the Nrf2 pathway in diabetic pancreatic tissue from mice. We found that Myrcene restored insulin levels by ~ 4-fold (4.01 ± 0.32) with reference to diabetic control, along with body weight, and reduced blood glucose levels by ~ 0.5-fold (11.53 ± 1.62). The administration of Myrcene increased high-density lipoprotein (HDL) (46.77 ± 3.90) and decreased many lipid profile markers compared with diabetic control, suggesting its hypolipidemic action. Later, docking results indicated that myrcene exhibits a higher binding affinity for Nrf2 than for other molecular targets, and western blot data showed that myrcene enhanced Nrf2 protein production. Myrcene exhibited antidiabetic, hypolipidemic, and antioxidative properties in HFD-STZ-induced diabetic mice, supporting its potential use as an antidiabetic supplement. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-026-04864-2.

Key Findings

• Myrcene administration restored insulin levels by approximately 4-fold in diabetic mice.
• Myrcene reduced blood glucose levels by about half and improved body weight in diabetic mice.
• Myrcene increased HDL levels and decreased lipid profile markers, showing hypolipidemic effects.
• Molecular docking showed myrcene has a higher binding affinity for Nrf2 than other targets.
• Western blot analysis confirmed myrcene enhanced Nrf2 protein expression in diabetic pancreatic tissue.

Clinical Significance

Citation

Pandey Ruchi, Ray Adarsh Kumar, Bisht Priyaet al.. NRF2 activation by myrcene restores redox balance and metabolic homeostasis in a mouse model of type 2 diabetes. 3 Biotech. 2026-Jun.