title: Honokiol, a natural plant product, inhibits inflammatory signals and alleviates inflammatory arthritis.
abstract: Honokiol (HNK), a phenolic compound isolated and purified from magnolia, has been found to have a number of pharmacologic benefits, including anti-angiogenic and anti-inflammatory properties. HNK has long been used in traditional Asian medicine without toxic side effects. We and others have extensively studied signaling to B cells by CD40 and its Epstein Barr viral mimic, latent membrane protein 1 (LMP1), which has been implicated in exacerbation of chronic autoimmune disease. We asked whether HNK could inhibit CD40 and LMP1 inflammatory signaling mechanisms. In vivo, HNK stabilized the severity of symptomatic collagen-induced arthritis in both CD40-LMP1 transgenic mice and their congenic C57BL/6 counterparts. Ex vivo studies, including collagen-specific serum Ab and Ag recall responses, as well as CD40 or LMP1-mediated activation of splenic B cells, supported the anti-inflammatory effects of HNK. In mouse B cell lines expressing the human CD40-LMP1 chimeric receptor, CD40- and LMP1-mediated NF-kappaB and AP-1 activation were abrogated in a dose-dependent manner, with a concomitant decrease in TNF-alpha and IL-6. These promising findings suggest that the nontoxic anti-inflammatory properties of HNK could be valuable for blocking the autoimmune response.
authors.affiliation: Department of Microbiology, University of Iowa, IA 52242, USA.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Munroe
authors.forename: Jack L
authors.initials: JL
authors.lastname: Arbiser
authors.forename: Gail A
authors.initials: GA
authors.lastname: Bishop
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D019013:CD40 Antigens / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D017705:Lignans / Q000627:therapeutic use*; D031566:Magnolia / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000187:drug effects; D008517:Phytotherapy; D028321:Plant Preparations / Q000627:therapeutic use; D047992:TNF Receptor-Associated Factor 2 / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000187:drug effects; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D018926:Anti-Allergic Agents; D001713:Biphenyl Compounds; D019013:CD40 Antigens; D017705:Lignans; D016328:NF-kappa B; D028321:Plant Preparations; D047992:TNF Receptor-Associated Factor 2; D018808:Transcription Factor AP-1; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols