Exploring pulegone in type 2 diabetes treatment: Molecular docking, influence on insulin resistance and modulation of pro/anti-inflammatory cytokines.

BACKGROUND

Type 2 diabetes involves insulin resistance, where muscle, liver, and fat cells fail to utilize glucose leading to hyperglycemia.

OBJECTIVES

This study explores the therapeutic potential of pulegone in type 2 diabetes by examining its molecular interactions with key metabolic targets and evaluating its effects on insulin resistance and inflammatory cytokine modulation.

METHODS

Except for normal controls, animals were fed a high-sucrose, high-fat diet for four months to induce insulin resistance. Treatment groups received metformin (150 mg/kg) or pulegone doses: low (5 mg/kg), medium (10 mg/kg), and high (15 mg/kg) for 45 days. Post-treatment, tissues and blood were collected. Blood serum was analyzed for liver markers, lipid profile, and blood for glycated hemoglobin. ELISA was used for cytokines (resistin, adiponectin, IL-1Ra, TNF-α), and qPCR assessed gene expression of NF-κB, TNF-α, PPAR-α/γ, IL-6, IL-10, IL-1Ra, and adiponectin. Histopathology was performed. Data were analyzed using GraphPad Prism. Molecular docking was conducted to identify the binding affinities of pulegone to target proteins.

RESULTS

Pulegone significantly reduced fasting blood glucose, glycated hemoglobin, triglycerides, cholesterol, and liver enzymes, while increasing HDL levels compared with diabetic controls. It also decreased serum resistin, TNF-α, IL-6 and NF-κB expression, while upregulating adiponectin, IL-10, PPAR-α, PPAR-γ and IL-1Ra. Histopathological examination showed protective effects on the pancreas, liver, kidney, heart, and aorta. Docking analysis favored strong binding affinities of pulegone with key targets.

CONCLUSION

Pulegone ameliorates insulin resistance by improving glycemic and lipid profiles, modulating pro- and anti-inflammatory cytokines, and protecting vital organs, suggesting its potential as a multitarget antidiabetic agent.