2. Academic Validation
  3. Ginkgolide A enhances FoxO1 expression and reduces endoplasmic reticulum stress to mitigate osteoarthritis in mice

Ginkgolide A enhances FoxO1 expression and reduces endoplasmic reticulum stress to mitigate osteoarthritis in mice

  • Int Immunopharmacol. 2024 Dec 5;142(Pt B):113116. doi: 10.1016/j.intimp.2024.113116.
Heng Yu 1,  Jinghao Liang 1,  Yingying Bao 2,  Kaiye Chen 1,  Yangcan Jin 1,  Xiang Li 1,  Hao Chen 1,  Yong Gou 1,  Keyu Lu 1,  Zhongke Lin 3
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 2 The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 3 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: zhongkelinspine@163.com.
PMID: 39288630 DOI: 10.1016/j.intimp.2024.113116
Abstract

This study aimed to investigate the effects of Ginkgolide A (GA) on chondrocytes under oxidative stress and to elucidate its potential molecular mechanisms. Using a destabilization of the medial meniscus (DMM) model in mice and an in vitro osteoarthritis (OA) model induced by tert-butyl hydroperoxide (TBHP) in chondrocytes, we validated the therapeutic efficacy and underlying mechanisms of GA. Potential OA targets of GA were identified through network pharmacology, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Further exploration into the effects on endoplasmic reticulum stress (ERS), Apoptosis, extracellular matrix (ECM) degradation, and Forkhead Box O1 (FoxO1) related pathways was conducted using Western blotting, immunofluorescence, TUNEL staining, flow cytometry, X-ray, micro-computed tomography (Micro-CT) analysis, and histological staining. The results demonstrated that GA upregulated FoxO1 expression and inhibited ERS-related signaling pathways, thereby reducing Apoptosis and ECM degradation. In conclusion, GA significantly alleviated OA symptoms both in vitro and in vivo, suggesting its potential as a therapeutic agent for OA.

Keywords

Apoptosis; Endoplasmic reticulum stress; FoxO1; Ginkgolide A; Network pharmacology; Osteoarthritis.

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