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.

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The objective of this research was to identify the existence of root exudation of organic acid in Lotus corniculatus germplasms subjected to toxic aluminum (Al) levels and investigate the effect of this mechanism on the Al content in the root tissue and in morphological parameters of plant development. Two experiments were performed in nutrient solution to evaluate the Al accumulation and exudation of organic acids, using cultivars INIA Draco and São Gabriel and genotypes UFRGS and UF-T2. The plants were cultivated in Al-free solution, which was applied on the 45th day in half of the pots of each genotype. Root exudation was highly correlated with the reduced accumulation of Al in the root tissue (r 2 = 0.75 at 72 h). Genotype UF-T2, selected for Al tolerance, extruded 80% more oxalic acid in the presence of Al compared with the other germplasms, indicating that this mechanism is involved with Al tolerance in L. corniculatus. This experiment showed strong evidence that L. corniculatus exhibits Type I tolerance, in which anionic channels are rapidly activated by Al exposure. Exudation of oxalic acid is likely a crucial mechanism that allows the maintenance of L. corniculatus growth when exposed to toxic Al conditions, and this characteristic should be used to identify tolerant genotypes in the future.