title: A novel naturally occurring salicylic acid analogue acts as an anti-inflammatory agent by inhibiting nuclear factor-kappaB activity in RAW264.7 macrophages.
abstract: Methyl salicylate 2-O-β-D-lactoside (DL0309), is a molecule chemically related to salicylic acid that is isolated from Gaultheria yunnanensis (FRANCH.) REHDER (G. yunnanensis). G. yunnanensis, a traditional Chinese herbal medicine, is widely used for treating rheumatoid arthritis, swelling, pain, trauma, and chronic tracheitis. In the present study, we explored the mechanism whereby DL0309 exerts anti-inflammatory effects, using the model of lipopolysaccharide (LPS)-treated RAW264.7 cells. We examined the effects of DL0309 on LPS-induced nuclear factor-kappaB (NF-κB) activity by Western blot analysis, cell imaging analysis and an electrophoretic mobility shift assay (EMSA). Production of pro-inflammatory cytokines was also measured. Our observations indicate that DL0309 suppressed production of nitric oxide (NO), reactive oxygen species (ROS) and the pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), in a concentration-dependent manner. The phosphorylation of IKK-β and degradation of IκB-α by LPS were both inhibited by DL0309 in the cytoplasm. The increased protein level of NF-κB by LPS in the nucleus was also reduced by DL0309. Consistent with these results, we found that DL0309 prevents the nuclear translocation and DNA binding activity of NF-κB. Finally, our results demonstrate that DL0309 exerts anti-inflammatory effects, by inhibiting the production of pro-inflammatory cytokines and suppressing of the activation of the NF-κB signaling pathway in LPS-treated macrophage cells. Therefore, DL0309 may have therapeutic potential for treating inflammatory diseases by regulating the NF-κB pathway and pro-inflammatory cytokine production.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No 1 Xiannongtan Street, Xicheng District, Beijing 100050, PR China.
authors.forename: Tiantai
authors.initials: T
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Lan
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.forename: Wenyu
authors.initials: W
authors.lastname: Xin
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhang
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D031282:Gaultheria / Q000737:chemistry; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020156:Salicylic Acid / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D020156:Salicylic Acid