Work

A diarylheptanoid from Alpinia officinarum ameliorates insulin resistance in 3T3-L1 adipocytes and db/db mice through modulation of PPARγ/PI3K/AKT signaling pathway

Year: 2026

Type: article

Abstract: Introduction: Hance and its diarylheptanoid metabolite, (R)-5-hydroxy-1,7-diphenyl-3-heptanone (DPHC), have hypoglycemic and hypolipidemic effects to ameliorate T2DM with insulin resistance (IR). However, the mechanisms by which DPHC ameliorates adipose IR associated with lipid metabolism disorders are not yet fully elucidated. Methods: DPHC was evaluated in dexamethasone-induced IR-3T3-L1 adipocytes and db/db mice. Exploratory network analysis was used to generate candidate mechanisms. Results: In IR-3T3-L1 adipocytes, DPHC increased glucose consumption and 2-NBDG uptake, reduced lipid accumulation and inflammatory-marker expression, and increased measured PPARγ and insulin-signaling-associated molecular markers. GW9662 attenuated several cellular effects of DPHC, supporting the involvement of a PPARγ-dependent component. In db/db mice, oral DPHC administration at 80 or 140 mg/kg/day reduced lipid accumulation and improved measured serum lipid-related endpoints. Pocket-directed docking to the DPHC-bound PPARγ ligand-binding domain, together with a single 100-ns molecular-dynamics trajectory, generated a structurally plausible binding pose. Conclusion: The findings support a testable model in which DPHC may alleviate adipocyte insulin resistance partly through PPARγ-associated PI3K/AKT regulation.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1934799