title: Disease modifying anti-rheumatic activity of the alkaloid montanine on experimental arthritis and fibroblast-like synoviocytes.
abstract: Montanine is an alkaloid isolated from Rhodophiala bifida bulb with potential anti-arthritic activity. In this context, we evaluated whether montanine has a disease modifying anti-rheumatic activity in two arthritis models and its effect in vitro on lymphocyte proliferation and on invasiveness of fibroblast-like synoviocytes (FLS). Antigen-induced arthritis (AIA) was performed in Balb/C mice with methylated bovine serum albumin, and nociception and leukocytes migration into the knee joint were evaluated. Collagen-induced arthritis (CIA) was performed in DBA/1J mice, and arthritis development and severity were assessed by clinical and histological scoring and articular nociception. Montanine was administered intraperitoneally twice a day. Lymphocyte proliferation stimulated by concanavalin A in 48h was performed with MTT assay, while FLS invasion in 24h was assayed in a Matrigel-coated transwell system. Administration of montanine decreased nociception (P<0.001) and leukocyte articular migration (P<0.001) in mice with AIA. In mice with CIA, treatment with montanine reduced severity of arthritis and joint damage assessed by clinical (P<0.001) and histological (P<0.05) scores and ameliorated articular nociception (P<0.05). In vitro, montanine inhibited lymphocyte proliferation stimulated with ConA (P<0.001) and decreased FLS invasion (P<0.05) by 54%, with an action independent of cytotoxicity. Our findings suggest that montanine can be further explored as an innovative pharmacological approach for autoimmune diseases such as arthritis.
authors.affiliation: Serviço de Reumatologia, Laboratório de Doenças Autoimunes, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Departamento de Medicina Interna, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: mirianfarinon@hotmail.com.
authors.forename: Mirian
authors.initials: M
authors.lastname: Farinon
authors.affiliation: Serviço de Reumatologia, Laboratório de Doenças Autoimunes, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Departamento de Medicina Interna, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: vaclarimundo@gmail.com.
authors.forename: Vanessa S
authors.initials: VS
authors.lastname: Clarimundo
authors.affiliation: Departamento de Produção de Matéria Prima, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: grazielepereiraramos@gmail.com.
authors.forename: Graziele P R
authors.initials: GP
authors.lastname: Pedrazza
authors.affiliation: Department of Medicine, Division of Rheumatology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: percio.gulko@mssm.edu.
authors.forename: Pércio S
authors.initials: PS
authors.lastname: Gulko
authors.affiliation: Departamento de Produção de Matéria Prima, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: zuanazzi@ufrgs.br.
authors.forename: José A S
authors.initials: JA
authors.lastname: Zuanazzi
authors.affiliation: Serviço de Reumatologia, Laboratório de Doenças Autoimunes, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Departamento de Medicina Interna, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: rxavier10@gmail.com.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Xavier
authors.affiliation: Serviço de Reumatologia, Laboratório de Doenças Autoimunes, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Departamento de Medicina Interna, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: patty.go@gmail.com.
authors.forename: Patricia G
authors.initials: PG
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000473:pathology*; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000070918:Synoviocytes / Q000187:drug effects* / Q000473:pathology*
chemical_list: D007546:Isoquinolines; C517208:montanine
keywords: Alkaloids; Antigen-induced arthritis; Collagen-induced arthritis; Experimental arthritis; Fibroblast-like synoviocytes; Montanine; Montanine (PubChem CID: 11087935); Saline (PubChem CID: 5234)