2. Academic Validation
  3. Gastrodin targets the system Xc-/GPX4 axis to inhibit abnormal proliferation of fibroblast-like synoviocytes and improve rheumatoid arthritis

Gastrodin targets the system Xc-/GPX4 axis to inhibit abnormal proliferation of fibroblast-like synoviocytes and improve rheumatoid arthritis

  • Phytomedicine. 2025 Feb 13:139:156493. doi: 10.1016/j.phymed.2025.156493.
Yanlu Li 1,  Aoyun Li 1,  Yanchao Xing 1,  Yingshan Jiang 1,  Hongyan Pei 1,  Zhongmei He 2,  Jianming Li 2,  Yan Zhao 2,  Kun Shi 2,  Ying Zong 3,  Rui Du 4
Affiliations

Affiliations

  • 1 College of Chinese Medicinal Material, Jilin Agricultural University, Changchun, Jilin Province, 130118, China.
  • 2 College of Chinese Medicinal Material, Jilin Agricultural University, Changchun, Jilin Province, 130118, China; Laboratory of Production and Product Application of Sika Deer of Jilin Province, Jilin Agricultural University, Changchun Jilin Province, 130118, PR China.
  • 3 College of Chinese Medicinal Material, Jilin Agricultural University, Changchun, Jilin Province, 130118, China; Laboratory of Production and Product Application of Sika Deer of Jilin Province, Jilin Agricultural University, Changchun Jilin Province, 130118, PR China. Electronic address: zongying@jlau.edu.cn.
  • 4 College of Chinese Medicinal Material, Jilin Agricultural University, Changchun, Jilin Province, 130118, China; Laboratory of Production and Product Application of Sika Deer of Jilin Province, Jilin Agricultural University, Changchun Jilin Province, 130118, PR China; Key Lab of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, Jilin Province, 130118, China. Electronic address: durui197101@sina.com.
PMID: 39970857 DOI: 10.1016/j.phymed.2025.156493
Abstract

Background: Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by the abnormal proliferation of Fibroblast-like Synoviocytes (FLS), leading to synovial hyperplasia and progressive joint destruction in an inflammatory environment. Gastrodin (GAS), the main active ingredient of Gastrodia elata, is also the basis for its anti-inflammatory, anti-tumor, and Other pharmacological effects. However, GAS's effects on RA and its specific molecular mechanisms remain to be thoroughly explored.

Purpose: This study combines transcriptomics and modern pharmacological methods to explore the molecular mechanism of GAS to ameliorate RA and provide a theoretical basis for the development of new therapeutic strategies for rheumatoid arthritis.

Methods: A rat Adjuvant arthritis (AA) model was established to further determine the molecular mechanism by which GAS affects RA based on transcriptomics and molecular docking. The pharmacological activity of GAS against RA was evaluated by in vivo experiments such as micro-CT, histopathological examination, transmission electron microscopy and Elisa. Primary FLS cells were also extracted from AA rats for in vitro experiments to reveal the potential of GAS in treating RA.

Results: Transcriptomic and molecular docking analyses suggested Ferroptosis as a potential mechanism for GAS to ameliorate RA. In vitro and in vivo studies demonstrated that GAS downregulates SLC7A11, impacts the antioxidant system, and inhibits GPX4. It facilitates lipopolysaccharide-induced Ferroptosis in RA-FLS (rheumatoid arthritis fibroblast-like synoviocytes) cells, suppresses synovial proliferation, and ameliorates rheumatoid arthritis.

Conclusion: This study reveals the molecular mechanism of the anti-RA action of GAS from a novel perspective, suggesting that GAS is a promising drug candidate for the treatment of RA.

Keywords

Gastrodin; Molecular docking; Rheumatoid arthritis; System Xc-/GPX4 Axis; Transcriptomics.

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