title: Methyl salicylate 2-O-β-d-lactoside alleviates the pathological progression of pristane-induced systemic lupus erythematosus-like disease in mice via suppression of inflammatory response and signal transduction.
abstract: Systemic lupus erythematosus (SLE), with a high incidence rate and insufficient therapy worldwide, is a complex disease involving multiple organs characterized primarily by inflammation due to deposition of immunocomplexes formed by production of autoantibodies. The mechanism of SLE remains unclear, and the disease still cannot be cured. We used pristane to induce SLE in female BALB/c mice. Methyl salicylate 2-O-β-d-lactoside (MSL; 200, 400, and 800 mg/kg) was orally administered 45 days after pristane injection for 4.5 months. The results showed that MSL antagonized the increasing levels of multiple types of antibodies and cytokines in lupus mice. MSL was found to suppress joint swelling and have potent inhibitory effect on arthritis-like symptoms. MSL also significantly decreased the spleen index and expression of inflammatory markers in the lupus mice. MSL protected the kidneys of lupus mice from injury through inhibiting the expression of inflammatory cytokines and reducing the IgG and C3 immunocomplex deposits. Further Western blot assays revealed that the downregulation of the intracellular inflammatory signals of NFκB and JAK/STAT3 might be the potential molecular mechanisms of the pharmacological activity of MSL against SLE in vivo. These findings may demonstrate that MSL has the potential to be a useful and highly effective treatment for SLE.
authors.affiliation: Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: He
authors.affiliation: Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Yi-Huang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Yu-Cai
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine, Guangzhou, People's Republic of China.
authors.forename: Jian-Song
authors.initials: JS
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000737:chemistry / Q000276:immunology*; D016207:Cytokines / Q000737:chemistry / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006027:Glycosides / Q000737:chemistry / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012459:Salicylates / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013729:Terpenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D006027:Glycosides; D012459:Salicylates; D013729:Terpenes; C008245:lactosides; C009042:pristane; C033069:methyl salicylate
keywords: inflammatory response; lupus nephritis; methyl salicylate 2-O-β-d-lactoside; signal transduction; systemic lupus erythematosus