2. Academic Validation
  3. Coptisine inhibits aggressive and proliferative actions of fibroblast like synoviocytes and exerts a therapeutic potential for rheumatoid arthritis

Coptisine inhibits aggressive and proliferative actions of fibroblast like synoviocytes and exerts a therapeutic potential for rheumatoid arthritis

  • Int Immunopharmacol. 2024 Jan 4:128:111433. doi: 10.1016/j.intimp.2023.111433.
Fangqiu Xu 1,  Chuyu Shen 2,  Shuoyang Zhang 2,  Yingli Liu 2,  Di Liu 2,  Yu Kuang 2,  Ruiru Li 2,  Cuicui Wang 3,  Xiaoyan Cai 4,  Maohua Shi 5,  Youjun Xiao 6
Affiliations

Affiliations

  • 1 Department of Clinical Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 2 Department of Rheumatology and Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 3 Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
  • 4 Department of Rheumatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China. Electronic address: [email protected].
  • 5 Department of Rheumatology, The First People's Hospital of Foshan, Foshan, Guangdong, China. Electronic address: [email protected].
  • 6 Department of Rheumatology and Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: [email protected].
PMID: 38181676 DOI: 10.1016/j.intimp.2023.111433
Abstract

Objective: Coptisine, a natural bioactive small molecular compound extracted from traditional Chinese herb Coptis chinensis, has been shown to exhibit anti-tumor effect. However, its contribution to autoimmune diseases such as rheumatoid arthritis (RA) is unknown. Here, we evaluate the effect of coptisine in controlling fibroblast-like synoviocytes (FLS)-mediated synovial proliferation and aggression in RA and further explore its underlying mechanism(s).

Methods: FLS were separated from synovial tissues obtained from patients with RA. Protein expression was measured by Western blot or immunohistochemistry. Gene expression was detected by quantitative RT-PCR. The EdU incorporation was used to measure cell proliferation. Migration and invasion were determined by Boyden chamber assay. RNA sequencing analysis was used to seek for the target of coptisine. The in vivo effect of coptisine was evaluated in collagen-induced arthritis (CIA) model.

Results: Treatment with coptisine reduced the proliferation, migration, and invasion, but not Apoptosis of RA FLS. Mechanistically, we identified PSAT1, an Enzyme that catalyzes serine/one-carbon/glycine biosynthesis, as a novel targeting gene of coptisine in RA FLS. PSAT1 expression was increased in FLS and synovial tissues from patients with RA compared to healthy control subjects. Coptisine treatment or PSAT1 knockdown reduced the TNF-α-induced phosphorylation of p38, ERK1/2, and JNK MAPK pathway. Interestingly, coptisine administration improved the severity of arthritis and reduced synovial PSAT1 expression in mice with CIA.

Conclusions: Our data demonstrate that coptisine treatment suppresses aggressive and proliferative actions of RA FLS by targeting PSAT1 and sequential inhibition of phosphorylated p38, ERK1/2, and JNK MAPK pathway. Our findings suggest that coptisine might control FLS-mediated rheumatoid synovial proliferation and aggression, and be a novel potential agent for RA treatment.

Keywords

Aggression; Coptisine; Fibroblast-like synoviocyte; PSAT1; Proliferation; Rheumatoid arthritis.

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