Journal List > J Rheum Dis > v.22(2) > 1064245

Cheon, Kim, Suh, Hur, Jo, Lim, Hah, Sung, Kwon, and Lee: Inhibitory Effects for Rheumatoid Arthritis of Dietary Supplementation with Resveratrol in Collagen-induced Arthritis

Abstract

Objective

Resveratrol is well-known for its anti-inflammatory, anti-oxidant effects on several diseases. We investigated whether dietary supplementation with resveratrol may suppress joint inflammation and destruction in a mouse model of collagen-in-duced arthritis (CIA).

Methods

Mice were randomly divided into two groups; CIA mice with normal diet-fed and CIA mice fed a 0.05% resveratrol diet. The effect of resveratrol on arthritis was assessed by clinical scoring system. The plain radiographs of paws were obtained to evaluate the effects on preventing bone destruction. Joint inflammation, cartilage damage, and osteoclastic bone resorption were checked by staining with H&E, Safranin-O, and tartrate resistant acid phosphatase (TRAP). Levels of pro-inflammatory cytokines were checked by enzyme-linked immunosorbent assay. The level of expression of nuclear factor (NF)-κ B was measured by electrophoretic mobility shift assay (EMSA).

Results

Dietary supplementation with resveratrol led to mitigated severity of arthritis compared to the normal diet group (6.7±0.8 vs. 2.7±0.6, p<0.01). Resveratrol-fed mice showed decreased bone destruction on radiograph (3.4±0.3 vs. 2.0±0.2, p<0.01), and showed significantly inhibited pathological changes (inflammation 2.0±0.3 vs.3.2±0.2, p<0.01; cartilage damage 1.5±0.3 vs. 3.2±0.2, p<0.01; pannus formation 1.4±0.3 vs. 3.0±0.3, p<0.01; erosion; 1.4±0.2 vs. 3.3±0.3, p<0.01). Generation of TRAP-positive osteoclasts was inhibited in the resveratrol-fed mice (55.3±12.7 vs. 3.27±0.8, p<0.01). Resveratrol-fed mice showed decreased levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein 1, and the soluble receptor activator of NF-κ B ligand in joint tissues and sera. Expression of NF-κ B, measured by EMSA, was decreased in resveratrol-fed mice.

Conclusion

Dietary supplementation with resveratrol mitigates inflammation and bone destruction in CIA mice.

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Figure 1.
Resveratrol feeding mitigates erythema and joint swelling in collagen-induced arthritis mice. (A) Representative images show the gross features of the hind paws on day 49. The normal diet-fed mice show more severe erythema and swelling (upper panel) compared with resveratrol-fed mice (lower panel). (B) The cumulative incidence of arthritis. The mice were considered arthritic when inflammation was observed in any paw with ≥2, and the incidence of arthritic mice in each group is shown as a percentage.(C) Weight of mice checked in each group was checked until day 49. (D) Clinical scores, as assessed by a visual arthritis scoring system were checked until day 49. (E) The hind paw thickness was measured on the indicated days after the primary immunization. Values are mean±standard error, n=10 mice for each group. *p<0.01 versus normal diet-fed mice.
jrd-22-93f1.tif
Figure 2.
Resveratrol feeding suppresses bone destruction in collagen-induced arthritis (CIA). The hind paws from CIA mice were taken for radiological analysis on day 49. (A) Representative radiographs of hindpaws. Normal diet-fed mice show severe bone erosion and joint damage (arrows) compared with resveratrol-fed CIA mice. (B) Quantitative analysis of bone destruction. Values are mean±standard error, n=10 mice for each group. *p<0.01 versus normal di-et-fed mice.
jrd-22-93f2.tif
Figure 3.
Resveratrol feeding reduces pathologic findings and osteoclastogenesis. (A) Representative histological features of ankle joints, hind paws from collagen-induced arthritis mice were obtained on day 49, sectioned, and stained with H&E, safranin-O, or tartrate resistant acid phosphatase (TRAP) (×100). (B) Quantitative scores of histological abnormalities. (C) Total number of TRAP-positive cells per field. Values are mean±standard drror, n=10 mice for each group. *p<0.01 versus normal diet-fed mice.
jrd-22-93f3.tif
Figure 4.
Resveratrol feeding decreases production of proinflammatory cytokines in joint tissues and sera of collagen-in-duced arthritis mice. The levels of pro-inflammatory cytokines in the joint homogenates (A) and sera (B) were measured by enzyme-linked immunosorbent assay. Values are mean±standard error, n=10 mice for each group. p<0.05 and *p<0.01 versus normal diet-fed mice. (C) The expression of nuclear factor (NF)-κ B was measured by electrophoretic mobility shift assay and shown the level of expression of NF-κ B was significantly decreased in resveratrol-fed mice. IL: interleukin, MCP: monocyte chemoattractant protein, sRANKL: soluble receptor activator of NF-κ B ligand, TNF: tumor necrosis factor.
jrd-22-93f4.tif
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