Acamprosate Protects Against Adjuvant-Induced Arthritis in Rats via Blocking the ERK/MAPK and NF-κB Signaling Pathway
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Osteoarthritis is a type of joint disease that results from the breakdown of joint cartilage and underlying bone and is believed to be caused by mechanical stress on the joint and low-grade inflammatory processes. Acamprosate significantly ameliorates the pathological features of experimental autoimmune encephalomyelitis due to its anti-inflammatory effect. The aims of the present study were to investigate the anti-arthritis activities of acamprosate and elucidate the underlying mechanisms. Adjuvant-induced arthritis (AIA) was induced by intradermal injection of complete Freund’s adjuvant. Male Wistar rats were randomly divided into five groups: (1) sham control group, (2) AIA group, (3) acamprosate 10 mg/kg (AIA + ACA10), (4) acamprosate 30 mg/kg (AIA + ACA30), and (5) acamprosate 100 mg/kg (AIA + ACA100). Paw swelling and the arthritis index were measured, and the production of IL-1β, IL-6, and TNF-α was detected by ELISA in serum. The expression of inflammation-related molecules, including c-Raf, ERK1/2, and NF-κB, was determined by Western blotting. We found that acamprosate significantly suppressed paw swelling and the arthritis index in AIA rats. Moreover, acamprosate also significantly suppressed the production of TNF-α, IL-1β, and IL-6 in serum, which is elevated by AIA induction. Finally, acamprosate inhibited p-c-Raf and p-ERK1/2 and NF-κB activation after AIA treatment. These results indicate that acamprosate has an anti-inflammatory effect on adjuvant-induced arthritic rats via inhibiting the ERK/MAPK and NF-κB signaling pathways, and acamprosate may serve as a promising novel therapeutic agent for osteoarthritis.
KEY WORDSacamprosate adjuvant-induced arthritis osteoarthritis inflammation ERK/MAPK NF-κB
This study was supported by National Natural Science Foundation of China (No. 81772311).
Conceived and designed the experiments: XS. Performed the experiments: PJ JR. Analyzed the data: SM WR. Wrote the paper: XS PJ.
Compliance with Ethical Standards
The experiment was approved by the ethical guidelines of the Zhejiang University Animal Experimentation Committee.
Conflicts of Interest
The authors declare that they have no competing interests.
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