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**13** 

*Japan* 

**Resveratrol: A Candidate Drug for** 

Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation of multiple joints, with disruption of joint cartilage. Accumulating evidence has pointed to inflammatory cytokines inducing hyperplasia of synovial cells in joints as an etiology for rheumatoid arthritis. High concentrations of cytokines such as tumor necrosis factor- (TNF-) and interleukin-1 (IL-1) are found in synovial fluid and plasma from patients with rheumatoid arthritis (Eastgate et al., 1988; Saxne et al., 1998) and those cytokines produce matrix metalloproteinases or activate osteoclasts, causing irreversible damage to soft tissues and bones (Olsen & Stein, 2004). Challenges for rheumatoid arthritis treatment, therefore, have been attempted using TNF- inhibitors, anti-TNF antibodies, a soluble TNF receptor-fusion protein, or an IL-1 receptor antagonist. A concern with these therapies, however, are side effects such as serious infections and inducible malignant

Resveratrol (Fig. 8), a phytoalexin that is present in grape skin and red wine, exerts a variety of actions to reduce superoxides, suppress carcinogenesis and angiogenesis, prevent diabetes mellitus, inhibit inflammation, and prolong life span (Elliott & Jirousek, 2008). Furthermore, resveratrol decreases plaque formation relevant to neurodegenerative diseases such as Alzheimer's disease and Huntington's disease (Karuppagounder et al., 2009). Of particular interest is that resveratrol is a potent and specific inhibitor of NF-B activation induced by TNF- or IL-1, and therefore, resveratrol might be a potential therapy for rheumatoid arthritis (Elmali et al., 2007; Molnar & Garai, 2005; Penberthy,

MH7A human rheumatoid arthritis synovial cells were obtained from the Riken cell bank (Ibaraki, Japan). Cells were cultured in a culture medium; RPMI-1640 (Wako, Osaka, Japan) supplemented with 10% heat-inactivated fetal bovine serum (FBS), penicillin (final concentration, 100 U/ml), and streptomycin (final concentration, 0.1 mg/ml), in a

**1. Introduction** 

2007).

**2.1 Cell culture** 

tumors (den Broeder et al., 2002).

**2. Materials and methods** 

humidified atmosphere of 5% CO2 and 95% air at 37°C.

**Treating Rheumatoid Arthritis** 

Tomoyuki Nishizaki and Takeshi Kanno *Division of Bioinformation, Department of Physiology, Hyogo College of Medicine* 

