Identification of phillyrin as a PPAR-γ ligand through network pharmacology and molecular modeling
- 1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012 China
- 2School of Life Sciences, Anhui University of Chinese Medicine, Hefei, 230012 China
Abstract
Insulin resistance is a core pathological hallmark of metabolic syndromes like type 2 diabetes mellitus. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a classical therapeutic target for improving insulin sensitivity, yet the clinical utility of its synthetic agonists faces diverse adverse reactions. We previously showed that phillyrin, an important component of Forsythia suspensa, could improve insulin resistance in obesity. However, its direct molecular targets remain not fully understood. Herein, we adopted a combined in silico and experimental approach to determine whether phillyrin could function as a ligand of PPAR-γ. We implemented a multi-scale strategy integrating network pharmacology, molecular modeling, with experimental verification. Network pharmacology analysis was employed to predict system-level targets and pathways associated with phillyrin. Subsequently, molecular docking and molecular dynamics simulations were conducted using computational chemistry methods to characterize the binding mode, dynamic stability, and binding free energy (MM-GBSA) of phillyrin within the PPAR-γ ligand-binding domain. Finally, key computational predictions were experimentally validated in insulin-resistant 3T3-L1 adipocytes and in a high-fat diet-induced murine model of insulin resistance.
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BibTeX
@article{huang2026identification,
title = {{Identification of phillyrin as a PPAR-γ ligand through network pharmacology and molecular modeling}},
author = {Ling Huang and Zhizheng Fang and Rongchun Han and Xiaohui Tong},
journal = {NPJ Systems Biology and Applications},
year = {2026},
month = jul,
doi = {10.1038/s41540-026-00780-6},
url = {https://doi.org/10.1038/s41540-026-00780-6},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Identification of phillyrin as a PPAR-γ ligand through network pharmacology and molecular modeling
AU - Ling Huang
AU - Zhizheng Fang
AU - Rongchun Han
AU - Xiaohui Tong
PY - 2026
DA - 2026/07/06
JO - NPJ Systems Biology and Applications
DO - 10.1038/s41540-026-00780-6
UR - https://doi.org/10.1038/s41540-026-00780-6
AB - Insulin resistance is a core pathological hallmark of metabolic syndromes like type 2 diabetes mellitus. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a classical therapeutic target for improving insulin sensitivity, yet the clinical utility of its synthetic agonists faces diverse adverse reactions. We previously showed that phillyrin, an important component of Forsythia suspensa, could improve insulin resistance in obesity. However, its direct molecular targets remain not fully understood. Herein, we adopted a combined in silico and experimental approach to determine whether phillyrin could function as a ligand of PPAR-γ. We implemented a multi-scale strategy integrating network pharmacology, molecular modeling, with experimental verification. Network pharmacology analysis was employed to predict system-level targets and pathways associated with phillyrin. Subsequently, molecular docking and molecular dynamics simulations were conducted using computational chemistry methods to characterize the binding mode, dynamic stability, and binding free energy (MM-GBSA) of phillyrin within the PPAR-γ ligand-binding domain. Finally, key computational predictions were experimentally validated in insulin-resistant 3T3-L1 adipocytes and in a high-fat diet-induced murine model of insulin resistance.
SN - 2056-7189
ER -