Resveratrol alleviates osteoarthritis progression by inhibiting NLRP3 inflammasome response via the AMPK/PPARγ signaling pathway
- 1School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710018, P.R. China
- 2College of Medical Technology, Guiyang Kangyang University, Guiyang, Guizhou 550081, P.R. China
- 3Department of Joint Surgery, Translational Medicine Center, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, P.R. China
Abstract
Osteoarthritis (OA) is a chronic, degenerative disease affecting joint tissue. Resveratrol (RES), a natural polyphenolic compound, has anti-inflammatory, antioxidant and anti-apoptotic effects in chondrocytes and macrophages, suggesting therapeutic potential for OA. The present study investigated the molecular mechanisms of RES in OA treatment through network pharmacology analysis and in vitro and in vivo experiments. Network pharmacology was performed to identify potential therapeutic targets and pathways. An OA cell model was established by treating SW1353 cells with IL-1β, followed by RES intervention without or with AMPK inhibitor to evaluate the effects on the AMPK/PPARγ signaling pathway, NLRP3 inflammasome response, and extracellular matrix (ECM) metabolism. For in vivo assays, OA mice were established through the destabilization of the medial meniscus (DMM) surgery, and administered RES through oral gavage. Histopathological changes, serum inflammatory factors and the expression of target proteins in articular cartilage were analyzed. Network pharmacology identified the AMPK/PPARγ pathway as a key mechanism underlying the therapeutic effects of RES in OA. In vitro, RES activated the AMPK/PPARγ pathway and inhibited the NLRP3 inflammasome response, thereby preserving ECM homeostasis in SW1353 cells. In vivo, RES alleviated OA progression by suppressing cartilage degeneration and synovitis, and regulating serum inflammatory levels. The target protein changes were consistent with the in vitro findings. The present study demonstrates that RES effectively regulates the NLRP3 inflammasome response by activating the AMPK/PPARγ signaling pathway, providing a valuable experimental foundation and potential clinical utility for RES as a complementary and alternative therapy for OA.
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BibTeX
@article{cui2026resveratrol,
title = {{Resveratrol alleviates osteoarthritis progression by inhibiting NLRP3 inflammasome response via the AMPK/PPARγ signaling pathway}},
author = {Shanshan Cui and Zifan Luo and Wen Qin and Bo Chen and Qiaoxia Zhang and Jianbing Ma and Jie Ma and Rui Zhang},
journal = {International Journal of Molecular Medicine},
year = {2026},
month = oct,
doi = {10.3892/ijmm.2026.6015},
url = {https://doi.org/10.3892/ijmm.2026.6015},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Resveratrol alleviates osteoarthritis progression by inhibiting NLRP3 inflammasome response via the AMPK/PPARγ signaling pathway
AU - Shanshan Cui
AU - Zifan Luo
AU - Wen Qin
AU - Bo Chen
AU - Qiaoxia Zhang
AU - Jianbing Ma
AU - Jie Ma
AU - Rui Zhang
PY - 2026
DA - 2026/10/14
JO - International Journal of Molecular Medicine
DO - 10.3892/ijmm.2026.6015
UR - https://doi.org/10.3892/ijmm.2026.6015
AB - Osteoarthritis (OA) is a chronic, degenerative disease affecting joint tissue. Resveratrol (RES), a natural polyphenolic compound, has anti-inflammatory, antioxidant and anti-apoptotic effects in chondrocytes and macrophages, suggesting therapeutic potential for OA. The present study investigated the molecular mechanisms of RES in OA treatment through network pharmacology analysis and in vitro and in vivo experiments. Network pharmacology was performed to identify potential therapeutic targets and pathways. An OA cell model was established by treating SW1353 cells with IL-1β, followed by RES intervention without or with AMPK inhibitor to evaluate the effects on the AMPK/PPARγ signaling pathway, NLRP3 inflammasome response, and extracellular matrix (ECM) metabolism. For in vivo assays, OA mice were established through the destabilization of the medial meniscus (DMM) surgery, and administered RES through oral gavage. Histopathological changes, serum inflammatory factors and the expression of target proteins in articular cartilage were analyzed. Network pharmacology identified the AMPK/PPARγ pathway as a key mechanism underlying the therapeutic effects of RES in OA. In vitro, RES activated the AMPK/PPARγ pathway and inhibited the NLRP3 inflammasome response, thereby preserving ECM homeostasis in SW1353 cells. In vivo, RES alleviated OA progression by suppressing cartilage degeneration and synovitis, and regulating serum inflammatory levels. The target protein changes were consistent with the in vitro findings. The present study demonstrates that RES effectively regulates the NLRP3 inflammasome response by activating the AMPK/PPARγ signaling pathway, providing a valuable experimental foundation and potential clinical utility for RES as a complementary and alternative therapy for OA.
SN - 1107-3756
SN - 1791-244X
ER -