Dataset Information

Potent anti-inflammatory and antiproliferative effects of gambogic acid in a rat model of antigen-induced arthritis.

ABSTRACT:

Background

We have previously reported a continuous activation of caspase-1 and increased interleukin (IL)-1? levels in early rheumatoid arthritis (RA). These observations raised the hypothesis that drugs targeting the IL-1? pathway, in addition to tumour necrosis factor (TNF), may be particularly effective for early RA treatment. We have recently identified gambogic acid as a promising therapeutic candidate to simultaneously block IL-1? and TNF secretion. Our main goal here was to investigate whether gambogic acid administration was able to attenuate inflammation in antigen-induced arthritis (AIA) rats.

Methods

Gambogic acid was administered to AIA rats in the early and late phases of arthritis. The inflammatory score, ankle perimeter, and body weight were evaluated during the period of treatment. Rats were sacrificed after 19 days of disease progression and paw samples were collected for histological and immunohistochemical evaluation.

Results

We found that inflammation in joints was significantly suppressed following gambogic acid administration. Histological and immunohistochemical evaluation of treated rats revealed normal joint structures with complete abrogation of the inflammatory infiltrate and cellular proliferation.

Conclusions

Our results suggest that gambogic acid has significant anti-inflammatory properties and can possibly constitute a prototype anti-inflammatory drug with therapeutic efficacy in the treatment of inflammatory diseases such as RA.

SUBMITTER: Cascao R

PROVIDER: S-EPMC3929289 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Potent anti-inflammatory and antiproliferative effects of gambogic acid in a rat model of antigen-induced arthritis.

Cascão Rita R Vidal Bruno B Raquel Helena H Neves-Costa Ana A Figueiredo Nuno N Gupta Vineet V Fonseca João Eurico JE Moita Luis Ferreira LF

Mediators of inflammation 20140130

<h4>Background</h4>We have previously reported a continuous activation of caspase-1 and increased interleukin (IL)-1β levels in early rheumatoid arthritis (RA). These observations raised the hypothesis that drugs targeting the IL-1β pathway, in addition to tumour necrosis factor (TNF), may be particularly effective for early RA treatment. We have recently identified gambogic acid as a promising therapeutic candidate to simultaneously block IL-1β and TNF secretion. Our main goal here was to inves ...[more]

PMID: 24623960

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Project description:Background:Resveratrol is a natural polyphenol found in berries, roots and wine that is well known to have anti-inflammatory and anti-oxidative properties. The anti-inflammatory effect has been reported for both immune cells and connective tissues, but only few studies have investigated effects on immune mediated inflammatory arthritis. None of which have studied this effect when combining resveratrol with methotrexate or adalimumab, two major drugs in the treatment of immune mediated inflammatory arthritis.We therefore aimed to investigate the anti-inflammatory effect of resveratrol alone and in combination with methotrexate or adalimumab in ex vivo models of immune mediated inflammatory arthritis. We furthermore aimed to describe any variations in this effect based on disease activity and cellular composition of the synovial fluid infiltrate. Methods:Synovial fluid mononuclear cells from patients with rheumatoid arthritis (n?=?7) and spondyloarthritis (n?=?7) were cultured for either 48 h or 21 days. In both models, synovial fluid mononuclear cells were treated with resveratrol alone or in combination with methotrexate or adalimumab. Monocyte chemoattractant protein 1, matrix metalloproteinase 3 and tartrate resistant acidic phosphatase were measured to quantify inflammation, enzymatic degradation and osteoclast differentiation, respectively. Results:Resveratrol reduced monocyte chemoattractant protein 1 production by synovial fluid mononuclear cells significantly (p?=?0.005) compared to untreated controls. The effect of resveratrol was greatest in cultures from patients with low disease activity, i.e. DAS28CRP???3.2 (p?=?0.022), and in cultures dominated by lymphocytes (p?=?0.03). Further, the combination of methotrexate and resveratrol significantly reduced monocyte chemoattractant protein 1 levels compared with methotrexate alone in cultures from patients with low disease activity (p?=?0.016), and in cultures with high lymphocyte count (p?=?0.011). Resveratrol did not significantly affect matrix metalloproteinase 3 and tartrate resistant acidic phosphatase production. Conclusion:Resveratrol has anti-inflammatory properties in our ex vivo model of immune mediated inflammatory arthritis. Results show an additive effect of resveratrol, when combined with methotrexate in samples dominated by lymphocytes and samples from patients with low disease activity. This suggests further investigations in vitro and whether this effect may also be present in a clinical setting.

Dataset Information

Potent anti-inflammatory and antiproliferative effects of gambogic acid in a rat model of antigen-induced arthritis.

Background

Methods

Results

Conclusions

Publications

Potent anti-inflammatory and antiproliferative effects of gambogic acid in a rat model of antigen-induced arthritis.

Similar Datasets

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