Disease modifying anti-rheumatic activity of the alkaloid montanine on experimental arthritis and fibroblast-like synoviocytes

作者：Farinon Mirian; Clarimundo Vanessa S; Pedrazza Graziele P R; Gulko Percio S; Zuanazzi Jose A S; Xavier Ricardo M; de Oliveira Patricia G

来源：European Journal of Pharmacology, 2017, 799: 180-187.

DOI：10.1016/j.ejphar.2017.02.013

• Experimental arthritis
• Collagen-induced arthritis
• Antigen-induced arthritis
• Fibroblast-like synoviocytes
• Alkaloids
• Montanine

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/1 J 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 48 h was performed with MTT assay, while FLS invasion in 24 h 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.

• 出版日期2017-3-15