**6. References**


the Bcl-XL mRNA, possibly mediated by FOXO, which causes disruption of mitochondrial membrane potentials, allowing cytochrome c release from the mitochondria into the cytosol, leading to activation of caspase-9 and the effector caspase-3 in a sirtuin 1-dependent manner. This represents a mitochondria-mediated caspase-dependent apoptotic pathway. Upregulation of the AIF mRNA by resveratrol, alternatively, suggests resveratrol-induced MH7A cell apoptosis via a mitochondria-mediated caspase-independent pathway. Moreover, upregulation of the p21 and p27 mRNAs by resveratrol may account for

Resveratrol induces apoptosis in MH7A human rheumatoid arthritis synovial cells, and does so with much higher potency than other polyphenols. It achieves this effect by decreasing Bcl-XL expression, which disrupts mitochondrial membrane potentials, allowing cytochrome c release from the mitochondria into the cytosol, thereby activating caspase-9 and the effector caspase-3 in a sirtuin 1-dependent manner, which induces apoptosis. In addition, AIF, p21, and p27 may also participate in resveratrol-induced MH7A cell apoptosis and growth inhibition. These findings imply that resveratrol may be capable of preventing hyperplasia of synovial cells in human rheumatoid arthritis. Resveratrol, thus,

Byun, H.S., Song, J.K., Kim, Y.R., Piao. L., Won, M., Park, K.A., Choi, B.L., Lee, H., Hong,

den Broeder, A., van de Putte, L., Rau, R., Schattenkirchner, M., Van Riel, P., Sander, O.,

Chen, Q., Ganapathy, S., Singh, K.P., Shankar, S. & Srivastava, R.K. (2010). Resveratrol

Eastgate, J.A., Symons, J.A., Wood, N.C., Grinlinton, F.M., di Giovine, F.S. & Duff, G.W.

Elmali, N., Baysal, O., Harma, A., Esenkaya, I. & Mizrak, B. (2007). Effects of resveratrol in

Elliott, P.J. & Jirousek, M. (2008). Sirtuins: Novel targets for metabolic disease. Current

Franco, J.G., de Moura1, E.G., Koury, J.C., Trotta1, P.A., Cordeiro, A., Souza, L.L., Almeida,

J.H., Park, J., Seok, J.H., Lee, Y.J., Kang, S.W. & Hur, G.M. (2008). Caspase-8 has an essential role in resveratrol-induced apoptosis of rheumatoid fibroblast-like

Binder, C., Fenner, H., Bankmann, Y., Velagapudi, R., Kempeni, J. & Kupper, H. (2002). A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-antibody adalimumab (D2E7) in patients with rheumatoid arthritis.

induces growth arrest and apoptosis through activation of FOXO transcription

(1988). Correlation of plasma interleukin-1 levels with disease activity in

N.A., Lima, N.daS., Pazos-Moura, C.C., Lisboa, P.C. & Passos, M.C. (2010). Resveratrol reduces lipid peroxidation and increases sirtuin 1 expression in adult

could be developed as a promising drug for treatment of rheumatoid arthritis.

resveratrol-induced inhibition of MH7A cell growth.

synoviocytes. Rheumatology 47:301-308.

The Journal of Rheumatology 9:2288-2298.

rheumatoid arthritis. Lancet 2:706-709.

inflammatory arthritis. Inflammation 30:1-6.

Opinion in Investigational Drugs 9:371-378.

factors in prostate cancer cells. PLoS One 5(12):e15288.

**5. Conclusion** 

**6. References** 

animals programmed by neonatal protein restriction. The Journal of Endocrinology 207:319-328.


**Part 4** 

**Exercise and Alternative Therapies** 

