2. Academic Validation
  3. Wogonin inhibits the migration and invasion of fibroblast-like synoviocytes by targeting PI3K/AKT/NF-κB pathway in rheumatoid arthritis

Wogonin inhibits the migration and invasion of fibroblast-like synoviocytes by targeting PI3K/AKT/NF-κB pathway in rheumatoid arthritis

  • Arch Biochem Biophys. 2024 Mar 27:109965. doi: 10.1016/j.abb.2024.109965.
Haixin Yang 1,  Cuizhen Liu 2,  Xiujuan Lin 3,  Xing Li 4,  Shan Zeng 5,  Zhaohui Gong 6,  Qiang Xu 7,  Detang Li 8,  Nan Li 9
Affiliations

Affiliations

  • 1 School of Traditional Chinese Medicine, Jinan University, 510632, Guangzhou, China. Electronic address: [email protected].
  • 2 The First Clinical College of Guangzhou University of Chinese Medicine, 510405, Guangzhou, China. Electronic address: [email protected].
  • 3 The First Clinical College of Guangzhou University of Chinese Medicine, 510405, Guangzhou, China. Electronic address: [email protected].
  • 4 Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University, 510630, Guangzhou, China. Electronic address: [email protected].
  • 5 Department of Rheumatology, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, China. Electronic address: [email protected].
  • 6 Department of Cardiovascular, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, 510405, Guangzhou, China. Electronic address: [email protected].
  • 7 Department of Rheumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address: [email protected].
  • 8 The First Clinical College of Guangzhou University of Chinese Medicine, 510405, Guangzhou, China; Department of Pharmacy, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, 510405, China. Electronic address: [email protected].
  • 9 School of Traditional Chinese Medicine, Jinan University, 510632, Guangzhou, China. Electronic address: [email protected].
PMID: 38552763 DOI: 10.1016/j.abb.2024.109965
Abstract

Background: Rheumatoid arthritis (RA) is currently an autoimmune inflammatory disease with an unclear pathogenesis. Fibroblast-like synoviocytes (FLSs) have tumor-like properties, and their activation and secretion of pro-inflammatory factors are important factors in joint destruction. Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid isolated from Scutellaria baicalensis root, has been shown to have significant anti-inflammatory, anti-oxidative stress, and anti-tumor effects in a variety of diseases. However, the role of wogonin in RA has not yet been demonstrated.

Purpose: To investigate the inhibitory effect of wogonin on the invasive behavior of fibroblast-like synoviocytes and to explore the mechanism of action of wogonin in RA.

Methods: CCK-8, EdU, cell migration and invasion, immunofluorescence staining, RT-qPCR, and protein blot analysis were used to study the inhibitory effects of wogonin on migration, invasion, and pro-inflammatory cytokine overexpression in the immortalized rheumatoid synovial cell line MH7A. The therapeutic effects of wogonin were validated in vivo using arthritis scores and histopathological evaluation of collagen-induced arthritis mice.

Results: Wogonin inhibited the migration and invasion of MH7A cells, reduced the production of TNF-α, IL-1β, IL-6, MMP-3 and MMP-9, and increased the expression of IL-10. Moreover, wogonin also inhibited the myofibrillar differentiation of MH7A cells, increased the expression of E-cadherin (E-Cad) and decreased the expression of α-smooth muscle actin (α-SMA). In addition, wogonin treatment effectively ameliorated joint destruction in CIA mice. Further molecular mechanism studies showed that wogonin treatment significantly inhibited the activation of PI3K/Akt/NF-κB signaling pathway in TNF-α-induced arthritic FLSs.

Conclusion: Wogonin effectively inhibits migration, invasion and pro-inflammatory cytokine production of RA fibroblast-like synoviocytes through the PI3K/Akt/NF-κB pathway, and thus wogonin, as a natural flavonoid, has great potential for treating RA.

Keywords

Fibroblast-like synoviocyte; Invasion; Migration; Rheumatoid arthritis; Wogonin.

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