A diarylheptanoid from Alpinia officinarum ameliorates insulin resistance in 3T3-L1 adipocytes and db/db mice through modulation of PPARγ/PI3K/AKT signaling pathway
- 1Key Laboratory of Emergency and Trauma of Ministry of Education, Department of Hepatopancreatobiliary Aurgery, The First Affiliated Hospital, Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmaceutical Sciences, Hainan Medical University
- 2Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Basic Medical Sciences, Hainan Academy of Medical Sciences, Hainan Medical University
- 3Institute of Clinical Medicine, The Second Affiliated Hospital of Hainan Medical University
Abstract
Introduction: Alpinia officinarum 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.
Related
- Bletilla striata-derived extracellular vesicles armed probiotic by supramolecular assembly ameliorates colitis via macrophage modulation and microbiota restoration.
- Inclisiran ameliorates diabetes-associated skeletal muscle remodeling through modulation of FOXO1/PDK4 and ER stress-UPR signaling
- Nutritional modulation of microbiome proteomics in insulin resistance
- Effect of BAP and Osmotic Regulators on the Germination of Synthetic Seeds of Sugarcane (Saccharum officinarum)
- Resistance to modulation of in vivo gene expression by genomic editing.
BibTeX
@article{chen2026diarylheptanoid,
title = {{A diarylheptanoid from Alpinia officinarum ameliorates insulin resistance in 3T3-L1 adipocytes and db/db mice through modulation of PPARγ/PI3K/AKT signaling pathway}},
author = {Qiongshen Chen and Yinghuan Wang and Jie Jiang and Peixia He and Zhenrui Xie and Mingyan Zhou and Zhuoxian Deng and Junqing Zhang and Xuguang Zhang and Qiushi Yin},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1934799},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1934799/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A diarylheptanoid from Alpinia officinarum ameliorates insulin resistance in 3T3-L1 adipocytes and db/db mice through modulation of PPARγ/PI3K/AKT signaling pathway
AU - Qiongshen Chen
AU - Yinghuan Wang
AU - Jie Jiang
AU - Peixia He
AU - Zhenrui Xie
AU - Mingyan Zhou
AU - Zhuoxian Deng
AU - Junqing Zhang
AU - Xuguang Zhang
AU - Qiushi Yin
PY - 2026
DA - 2026/10/14
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1934799
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1934799/full
AB - Introduction: Alpinia officinarum 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.
SN - 1663-9812
ER -