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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.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Farinon M,Clarimundo VS,Pedrazza GP,Gulko PS,Zuanazzi JA,Xavier RM,de Oliveira PG

doi

10.1016/j.ejphar.2017.02.013

subject

Has Abstract

pub_date

2017-03-15 00:00:00

pages

180-187

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(17)30080-8

journal_volume

799

pub_type

杂志文章

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