The in vitro and in vivo anti-flammatory properties and cytotoxicity of extracts of Euphorbia hirta

Asthma is considered one of the most common respiratory complaints in the world today but a medical cure for this condition is currently not available. The use of herbal medicines to treat asthma has however been reported and Euphorbia hirtais one such herb. The alkaloids, flavonoids, glycosides, sterols, tannins and triterpenoids in E. hirta appear to exert the anti-asthma effects reported. In the first part of this study, the aqueous, acetone, dichloromethane and hexane extracts of E. hirta were evaluated for their effects on the lysosomal membrane integrity, cell viability and cell number of MRC-5 cell-line using the NR/MTT/CV assay. Hydrocortisone was used as a pharmaceutical control. The differences between the effects of the different extracts were investigated and the effects of the extracts were compared with hydrocortisone. Results obtained showed that hydrocortisone was relatively toxic to the MRC-5 cells whereas all four extracts studied showed very limited cytotoxic effects, with the aqueous extracts generally exhibiting the least effects. In the second part of this study, the effects of the aqueous E. hirta extract on the blood coagulation system and general airway wall microstructure and ultrastructure were investigated using the BALB/c mouse asthma model. Hydrocortisone was also used as a pharmaceutical control. Parameters studied included inflammatory cell population in peripheral blood and their migration into the lung parenchyma; platelet aggregation and fibrin fibre morphology; fibroblast and mucous cell proliferation; alveolar cell numbers, lamellar body formation as well as filopodia formation. The animal weights were continuously being monitored throughout the study. Results from the animal studies showed that the aqueous extract of E. hirta had limited effects on changes in the animal weights and did not cause fragility of blood fibrin fibres nor change the integrity and morphology of the platelets in the mice as seen in those treated with hydrocortisone. E. hirta extracts also significantly reduced the number of active inflammatory cells (especially neutrophils, eosinophils and basophils); restored the histological alterations observed in respiratory structures studied and had diverse, dose-dependent beneficial ultrastructural effects like reduction of smooth muscle hypertrophy, inhibition of macrophages into the airway parenchyma, among others. The final judgment and conclusion of this study was that the aqueous E. hirta extract did not show cytotoxic effects and could be used for the treatment of asthma in the BALB/c mice at doses ranging 25-62.5mg/kg. Further research leading to clinical trials is recommended after testing the potency of equivalent doses of this extract in other animal asthma models.Thesis (PhD)--University of Pretoria, 2008.AnatomyPhDUnrestricte

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

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