Methyl salicylate lactoside inhibits inflammatory response of fibroblast-like synoviocytes and joint destruction in collagen-induced arthritis in mice.

Abstract

BACKGROUND AND PURPOSE:

Methyl salicylate 2-O-β-d-lactoside (MSL), whose chemical structure is similar to that of salicylic acid, is a natural product derivative isolated from a traditional Chinese herb. The aim of this study was to investigate the therapeutic effect of MSL in mice with collagen-induced arthritis (CIA) and explore its underlying mechanism.

EXPERIMENTAL APPROACH:

The anti-arthritic effects of MSL were evaluated on human rheumatoid fibroblast-like synoviocytes (FLS) in vitro and CIA in mice in vivo by obtaining clinical scores, measuring hind paw thickness and inflammatory cytokine levels, radiographic evaluations and histopathological assessments.

KEY RESULTS:

Treatment with MSL after the onset of arthritis significantly prevented the progression and development of rheumatoid arthritis (RA) in CIA mice without megascopic gastric mucosa damage. In addition, MSL inhibited the production of pro-inflammatory mediators, the phosphorylation and translocation of NF-κB, and cell proliferation induced by TNF-α in FLS. MSL non-selectively inhibited the activity of COX in vitro, but was a more potent inhibitor of COX-2 than COX-1. MSL also inhibited the phosphorylation of inhibitor of NF-κB kinase, IκBα and p65, thus blocking the nuclear translocation of NF-κB in TNF-α-stimulated FLS.

CONCLUSION AND IMPLICATIONS:

MSL exerts therapeutic effects on CIA mice, suppressing the inflammatory response and joint destruction by non-selectively inhibiting the activity of COX and suppressing activation of the NF-κB signalling pathway, but without damaging the gastric mucosa. Therefore, MSL has great potential to be developed into a novel therapeutic agent for the treatment of RA.

• Authors: Wenyu Xin, Chao Huang, Xue Zhang, Sheng Xin, Yiming Zhou, Xiaowei Ma, Dan Zhang, Yongjie Li, Sibai Zhou, Dongming Zhang, Tiantai Zhang, Guanhua Du
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 171 Issue 14 Pg. 3526-38 (Jul 2014) ISSN: 1476-5381 [Electronic] England
• PMID: 24712652 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The British Pharmacological Society.

Chemical References

• Antirheumatic Agents
• Inflammation Mediators
• Salicylates
• Tumor Necrosis Factor-alpha
• methyl salicylate 2-O-lactoside
• Collagen
• Lactose

Topics

• Animals
• Ankle Joint (drug effects, metabolism, pathology)
• Antirheumatic Agents (chemistry, pharmacology)
• Arthritis, Experimental (chemically induced, drug therapy, pathology)
• Cell Proliferation (drug effects)
• Collagen
• Humans
• Inflammation (drug therapy, metabolism)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Lactose (analogs & derivatives, chemistry, pharmacology)
• Male
• Mice
• Mice, Inbred DBA
• Rats
• Rats, Wistar
• Salicylates (chemistry, pharmacology)
• Synovial Membrane (drug effects, metabolism, pathology)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism)