Regulation of cellar cytokine production and NF-κB pathway by ginseng and ginsenosides

Zhou, Y 2012, Regulation of cellar cytokine production and NF-κB pathway by ginseng and ginsenosides, Doctor of Philosophy (PhD), Health Sciences, RMIT University.


Document type: Thesis
Collection: Theses

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Title Regulation of cellar cytokine production and NF-κB pathway by ginseng and ginsenosides
Author(s) Zhou, Y
Year 2012
Abstract COPD is characterised by persistent inflammation in the airway and the lung which results in airway obstruction. Various inflammatory cells and mediators have been involved in the pathogenesis of COPD, in particular TNF-α through NF-κB signalling pathway. Current treatments for COPD are still not satisfactory and there is a need to develop new therapies targeting inflammatory mechanisms of COPD. Ginseng is a well-known medicinal herb and has been used in the treatment of COPD. Understanding the anti-inflammatory mechanism of ginseng and ginseng based formulas will facilitate the development of novel agents for treating COPD and other inflammatory diseases. In my project, we found G115, GHMF-III, Rb1, Rg1, Rg3, CK and Rh1, but not Rh2 significantly inhibited the release of TNF-α in LPS-induced u937 cells. GHMF-III, G115, Rb1 and Rg1 also inhibited the release of IL-1β and IL-6. Among the GHMFs tested, GHMF-III seemed to be the most potent. In addition, G115, GHMF-III, Rb1, Rg1, Rh1 and CK, but not Rh2 significantly inhibited the expression of IKK, p-IKK, IκBα, p-IκBα, p65 and p-p65 and decreased the transcriptional activity of NF-κB. G115, GHMF-III and Rg1, but not Rb1, Rh1, CK and Rh2 significantly increased the cellular level of cAMP and the expression of p-CREB, but inhibited the activity of PDE4 induced by LPS. These findings indicate that ginseng and ginseng related products have a significant inhibition of cytokine release and activation of NF-κB pathway in LPS-induced U937 cells. In addition, they may also act as PDE4 inhibitor to regulate cAMP pathway. Such actions of ginseng and ginseng related products may contribute to its therapeutic efficacy against COPD.

A separate research objective in the present study was to evaluate the clinical efficacy of TNF-α inhibitors in the treatment of the progression of joint damage (JD) in active rheumatoid Arthritis (RA). The rational of this research is that there is a wide use TNF-α inhibitors in the management of JD in active RA, although it is not clear if there are differences between these inhibitors when used alone or in combination with Methotrexate (MTX), and which factors may affect their efficacy. A meta-analysis was conducted to compare the effects of TNF-α inhibitors on the radiological progression (RP) of active RA when used alone or combined with MTX, and to study the correlation between the degree of activity of RA and the efficacy of TNF-α inhibitors on the progression of JD. It was found that TNF-α inhibitors showed a better efficacy than TNF-α inhibitors used alone. Among different types of TNF-α inhibitors, infliximab in combination with MTX exhibited a better efficacy than other types of TNF-α inhibitors. CRP, ESR and DAS28 were factors affecting the efficacy of TNF-α inhibitors on the progression of JD in active RA. These findings may help to guide clinical use of TNF-α inhibitors to control the progression of JD in active RA.
Degree Doctor of Philosophy (PhD)
Institution RMIT University
School, Department or Centre Health Sciences
Keyword(s) TNF-α
NF-κB
cAMP
Ginseng
G115
Ginsenoside
RA
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