title: MAPK/AP-1-Targeted Anti-Inflammatory Activities of Xanthium strumarium.
abstract: Xanthium strumarium L. (Asteraceae), a traditional Chinese medicine, is prescribed to treat arthritis, bronchitis, and rhinitis. Although the plant has been used for many years, the mechanism by which it ameliorates various inflammatory diseases is not yet fully understood. To explore the anti-inflammatory mechanism of methanol extracts of X. strumarium (Xs-ME) and its therapeutic potential, we used lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells and human monocyte-like U937 cells as well as a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model. To find the target inflammatory pathway, we used holistic immunoblotting analysis, reporter gene assays, and mRNA analysis. Xs-ME significantly suppressed the up-regulation of both the activator protein (AP)-1-mediated luciferase activity and the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor (TNF)-[Formula: see text]. Moreover, Xs-ME strongly inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW264.7 and U937 cells. Additionally, these results highlighted the hepatoprotective and curative effects of Xs-ME in a mouse model of LPS/D-GalN-induced acute liver injury, as assessed by elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and histological damage. Therefore, our results strongly suggest that the ethnopharmacological roles of Xs-ME in hepatitis and other inflammatory diseases might result from its inhibitory activities on the inflammatory signaling of MAPK and AP-1.
authors.affiliation: * Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.|† Department of Animal Science, Patuakhali Science and Technology University, Patuakhali 8602, Bangladesh.
authors.forename: Muhammad Jahangir
authors.initials: MJ
authors.lastname: Hossen
authors.affiliation: ‡ School of Systems Biomedical Science, Soongsil University, Seoul 06978, Republic of Korea.
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.affiliation: * Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000502:physiology*; D058990:Molecular Targeted Therapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000502:physiology*; D020298:U937 Cells; D031210:Xanthium / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases
keywords: AP-1; Hepatoprotectivity; MAPK; Pro-inflammatory Cytokines; Xanthium strumarium