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

Haixin Yang; Cuizhen Liu; Xiujuan Lin; Xing Li; Shan Zeng; Zhaohui Gong; Qiang Xu; Detang Li; Nan Li

doi:10.1016/j.abb.2024.109965

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

Arch Biochem Biophys. 2024 May:755:109965. doi: 10.1016/j.abb.2024.109965. Epub 2024 Mar 27.

Authors

Haixin Yang¹, Cuizhen Liu², Xiujuan Lin³, Xing Li⁴, Shan Zeng⁵, Zhaohui Gong⁶, Qiang Xu⁷, Detang Li⁸, Nan Li⁹

Affiliations

¹ School of Traditional Chinese Medicine, Jinan University, 510632, Guangzhou, China. Electronic address: 1765320026@qq.com.
² The First Clinical College of Guangzhou University of Chinese Medicine, 510405, Guangzhou, China. Electronic address: 18320429912@163.com.
³ The First Clinical College of Guangzhou University of Chinese Medicine, 510405, Guangzhou, China. Electronic address: linxiujuan0302@163.com.
⁴ Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University, 510630, Guangzhou, China. Electronic address: eandclx@163.com.
⁵ Department of Rheumatology, The First Affiliated Hospital of Jinan University, 510632, Guangzhou, China. Electronic address: zs870103@126.com.
⁶ Department of Cardiovascular, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, 510405, Guangzhou, China. Electronic address: 403978194@qq.com.
⁷ State Key Laboratory of Traditional Chinese Medicine Syndrome, Department of Rheumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address: fjksg@163.com.
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: lidetang2002@163.com.
⁹ School of Traditional Chinese Medicine, Jinan University, 510632, Guangzhou, China. Electronic address: linandada@126.com.

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.