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This dissertation, Effects of Ganoderma Lucidum on Rheumatoid Synovial Fibroblasts by Yee-wa, Eva, Ho, 何綺華, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Effects of Ganoderma Lucidum on Rheumatoid Synovial Fibroblasts submitted by EVA YEE WA HO for the Degree of Master of Philosophy at the University of Hong Kong in December 2003 Rheumatoid arthritis (RA) is a prototypical chronic inflammatory disease manifested by progressive synovial joint inflammation and erosion of the subchondral bone. The severity of the joint inflammation fluctuates over time, and the outcome in uncontrolled disease is progressive joint destruction, deformity, and disability. Efficacy of currently used antirheumatic therapy is often limited and frequent problems are side effects, either cumulative or idiosyncratic, and high cost. Abnormal proliferation of synovial fibroblasts and excessive secretion of pro-inflammatory cytokines such as interleukin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1 are the main destructive effects of synovial fibroblasts in RA joint. Ganoderma lucidum (Leyss, Ex Fr.), is a medicinal mushroom. G. lucidum polysaccharides, one of the main effective components of G. lucidum, have been reported to be effective in modulating immune functions. The reactions of different types of cells in the immune system to G. lucidum were not the same (Zhu & Mori 1994). This may explain the reason that G. lucidum has been used in various human diseases such as hepatitis, hypertension, arthritis, bronchitis and tumorigenic diseases in oriental folk medicine (Seong et al 1999). Many RA patients have claimed G. lucidum can to some extent alleviate the symptoms of their arthritis condition. In addition, G. lucidum has been shown to have immuno-modulatory, anti-inflammatory and analgesic effects in preclinical studies (Wasser and Weis 1999; Giner-Larza et al 2001). G. lucidum has been shown to modulate production of several cytokines, such as tumor necrosis factor (TNF)-α and ILs such as IL-1β, IL-2 and IL-6, which are all associated with the pathogenesis of RA (Ye et al 2001). Up to my knowledge, there has been no research of G. lucidum on RA synovial fibroblast. Therefore, I would like to find out the scientific evidence to support the potential use of G. lucidum in RA therapy. The aim of this project is to elucidate the effects of G. lucidum polysaccharides on RA synovial fibroblasts. Synovial tissues were obtained from patients with RA at the time of surgery; isolated synovial fibroblasts were used at passage of 6 or over. Preliminary experiments have shown that G. lucidum had significant inhibitory effect on the proliferation of RA synovial fibroblast. G. lucidum did not have any stimulatory effects on RA synovial fibroblasts in the production of IL-10, IL-1β and TNF-α. On the other hand, G. lucidum had slight stimulatory effects on the basal production of IL-6 and MCP-1. However, the actual stimulatory effects were minimal due to the low basal values. IL- 1β and LPS were used to mimic the actual environment in active RA joints. Results showed that G. lucidum significantly suppressed either IL-1β or LPS induced IL-8 and MCP-1 production. The inhibitory effects of G. lucidum on RA synovial fibroblast are at least in part, by inhibiting NF-κB transcription pathway. More experiments are required for further investigation on the potential use of G. lucidum in RA therapy. This pilot study demonstrated that G. lucidum is a non-toxic medicine and has immunomodulatory effects on cytokine produ

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