Zhang Xue, Sun Jialin, Xin Wenyu, Li Yongjie, Ni Lin, Ma Xiaowei, Zhang Dan, Zhang Dongming, Zhang Tiantai, Du Guanhua
Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100050, China.
Pharmacy Department of the Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Int Immunopharmacol. 2015 Mar;25(1):88-95. doi: 10.1016/j.intimp.2015.01.024. Epub 2015 Jan 28.
Methyl salicylate 2-O-β-D-lactoside (MSL) is a derivative of natural salicylate isolated from Gaultheria yunnanensis (Franch.) Rehder, which is widely used for treating rheumatoid arthritis (RA), swelling and pain. The aim of the present study was to investigate the effect of MSL on the progression of adjuvant-induced arthritis (AIA) in rat in vivo and explore the anti-inflammatory effects and mechanism of MSL in lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells in vitro. Our results showed that MSL significantly inhibited the arthritis progression in AIA rats, decreasing the right hind paw swelling and ankle diameter, attenuating histopathological changes and suppressing the plasma levels of TNF-α and IL-1β in AIA rats. Besides, MSL had potent anti-inflammatory effects on the LPS-activated RAW264.7. MSL dose-dependently inhibited the activity of COX-1, and COX-2. Moreover, MSL prominently inhibited LPS-induced activation of MAPK in RAW264.7 cells by blocking phosphorylation of p38 and ERK. Our study suggests that MSL may be effective in the treatment of inflammatory diseases by inhibiting the pro-inflammatory cytokine production and regulating the MAPK signal pathway.
水杨酸甲酯2 - O -β - D -乳糖苷(MSL)是从滇白珠树(Gaultheria yunnanensis (Franch.) Rehder)中分离出的天然水杨酸盐衍生物,广泛用于治疗类风湿性关节炎(RA)、肿胀和疼痛。本研究旨在探讨MSL对大鼠体内佐剂性关节炎(AIA)进展的影响,并在体外探索MSL对脂多糖(LPS)处理的小鼠巨噬细胞RAW264.7细胞的抗炎作用及机制。我们的结果表明,MSL显著抑制AIA大鼠的关节炎进展,减小右后爪肿胀和踝关节直径,减轻组织病理学变化,并抑制AIA大鼠血浆中TNF-α和IL-1β的水平。此外,MSL对LPS激活的RAW264.7细胞具有强大的抗炎作用。MSL剂量依赖性地抑制COX-1和COX-2的活性。此外,MSL通过阻断p38和ERK的磷酸化,显著抑制LPS诱导的RAW264.7细胞中MAPK的激活。我们的研究表明,MSL可能通过抑制促炎细胞因子的产生和调节MAPK信号通路,有效地治疗炎症性疾病。