Effect of Clinacanthus nutans extract on insulin-resistant HepG2 cells through PI3K/Akt and MAPK pathway modulation

Abstract

OBJECTIVES: This study investigated the effect of Clinacanthus nutans (CN), a traditional medicinal herb, on insulin resistance associated with type 2 diabetes mellitus (T2DM) and its underlying molecular mechanisms. METHODS: An insulin-resistant HepG2 cell model was established using glucosamine stimulation. CN aqueous extract was assessed for its effects on glucose consumption, glycogen synthesis, lipid accumulation, and key enzyme activities. Western blotting was employed to analyze changes in the insulin signaling pathways. RESULTES: CN treatment significantly improved glucose uptake, increased glycogen content, reduced triglyceride and cholesterol levels, and restored activities of glycolytic enzymes (HK, PK) while suppressing gluconeogenic enzymes (PEPCK, G6Pase). Mechanistically, CN activated the PI3K/Akt/mTOR signaling axis and inhibited phosphorylation of stress-related kinases in the MAPK pathway (JNK, ERK, p38, and MEK), thereby improving insulin sensitivity. CONCLUSIONS: These findings suggest that CN exerts multi-target regulatory effects and holds promise as a natural therapeutic candidate for T2DM management.