title: Boldine suppresses dextran sulfate sodium-induced mouse experimental colitis: NF-κB and IL-6/STAT3 as potential targets.
abstract: Ulcerative colitis (UC) is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration, and upregulation of inflammatory mediators. Boldine is an alkaloid compound found in Boldo tree, with multiple pharmacological actions, mainly anti-inflammatory, antioxidant, antitumor, and immunomodulatory activities. Hence, the effect of boldine for its anti-inflammatory properties against dextran sulfate sodium (DSS)-induced UC in BALB/c mice was studied. Administration of boldine to DSS-induced mice protects colon damage by reduced disease activity index, spleen weight, and increased colon length. Also administration of boldine showed a reduction in the activity of myeloperoxidase (MPO) and CD 68+ expression. Boldine reduced the colon damage, with significant reductions in both the extent and the severity of the inflammation as well as in crypt damage and leukocyte infiltration in the mucosa. Analysis in vivo showed clear decrease in the production of tumor necrosis factor (TNF)-α, Interleukin (IL)-6, IL-17, and signal transducer and activator of transcription-(p-STAT3)(Y705) with nuclear factor (p65-NF-κB) production being reduced significantly. Moreover, p65-NF-κB activation was reduced in mouse macrophage RAW 264.7 cells in vitro. The data demonstrated that boldine may be beneficial in colitis through selective immunomodulatory effects, which may be mediated, at least in part, by inhibition of p65-NF-κB and STAT3 signaling pathways. © 2016 BioFactors, 42(3):247-258, 2016.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50503 Kuala Lumpur, Malaysia.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Pandurangan
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50503 Kuala Lumpur, Malaysia.
authors.forename: Nooshin
authors.initials: N
authors.lastname: Mohebali
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50503 Kuala Lumpur, Malaysia.
authors.forename: Mohadeseh
authors.initials: M
authors.lastname: Hasanpourghadi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50503 Kuala Lumpur, Malaysia.
authors.forename: Chung Yeng
authors.initials: CY
authors.lastname: Looi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50503 Kuala Lumpur, Malaysia.
authors.forename: Mohd Rais
authors.initials: MR
authors.lastname: Mustafa
authors.affiliation: Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia.|Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia.
authors.forename: Norhaizan
authors.initials: N
authors.lastname: Mohd Esa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage; D001060:Aporphines / Q000008:administration & dosage*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics*; D000067996:RAW 264.7 Cells; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001060:Aporphines; D016264:Dextran Sulfate; D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D051996:Transcription Factor RelA; D000093242:Interleukin-6 Inhibitors; C498144:Rela protein, mouse; C494087:Stat3 protein, mouse; C011686:boldine
keywords: NF-κB; STAT3; boldine; enzymic antioxidants; ulcerative colitis