Xin Wenyu, Huang Chao, Zhang Xue, Xin Sheng, Zhou Yiming, Ma Xiaowei, Zhang Dan, Li Yongjie, Zhou Sibai, Zhang Dongming, Zhang Tiantai, Du Guanhua
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai, China; Binzhou Medical University, Yantai, China.
Br J Pharmacol. 2014 Jul;171(14):3526-38. doi: 10.1111/bph.12715.
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.
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.
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.
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.
水杨酸甲酯2 - O-β - d - 乳糖苷（MSL）的化学结构与水杨酸相似，是从一种传统中药中分离出的天然产物衍生物。本研究旨在探讨MSL对胶原诱导性关节炎（CIA）小鼠的治疗作用，并探究其潜在机制。
通过获取临床评分、测量后爪厚度和炎症细胞因子水平、影像学评估和组织病理学评估，在体外对人类风湿性成纤维细胞样滑膜细胞（FLS）以及在体内对CIA小鼠评估MSL的抗关节炎作用。
关节炎发作后用MSL治疗可显著阻止CIA小鼠类风湿性关节炎（RA）的进展和发展，且不会造成肉眼可见的胃黏膜损伤。此外，MSL抑制促炎介质的产生、NF - κB的磷酸化和转位，以及FLS中TNF - α诱导的细胞增殖。MSL在体外非选择性地抑制COX的活性，但对COX - 2的抑制作用比对COX - 1更强。MSL还抑制NF - κB激酶抑制剂、IκBα和p65的磷酸化，从而阻断TNF - α刺激的FLS中NF - κB的核转位。
MSL对CIA小鼠具有治疗作用，通过非选择性抑制COX活性和抑制NF - κB信号通路的激活来抑制炎症反应和关节破坏，但不会损伤胃黏膜。因此，MSL具有很大的潜力被开发成为治疗RA的新型治疗药物。
