RESUMEN
The anti-inflammatory properties of Euphol (EU) a diterpene, isolated from the rhizomes of the plant Euphorbia acaulis, were evaluated. This study was designed to examine the effects of EU on inflammation in a rat model of pleurisy compared with a steroidal anti-inflammatory drug (DEX, dexamethasone). The rat model of pleurisy was used to evaluate the effectiveness of EU on leukocyte migration, exudation volume, proinflammatory cytokines i.e. Tumor Necrosis factor α (TNFα), Interleukin-1 (IL-1β) and Interleukin-6 (IL-6) as well as on proinflammatory mediators PGE2, nitrite/nitrate levels, and LTB4. Pleurisy was induced by carrageenan (cg ), administered by intra pleural route (i.pl.) and the leukocyte infiltration and inflammatory parameters analyzed 4 h after pleurisy induction. EU (8mg/kg-1, p.o.) treated groups caused significant decrease in the infiltration of neutrophils and exudate volume . There was an observed marked reduction in TNFα, IL-1β and IL-6 levels. Flow cytometric analysis of intracellular TNFα by leukocytes present in pleural exudates showed a significant decrease relative to the total extracellular TNFα inhibition in the pleural fluid. The proinflammatory mediators PGE2, LTB4 release and the nitrite/nitrate levels were remarkably deregulated which are interrelated to TNFα and IL-1β levels.
RESUMEN
The premise of the present investigation was to evaluate the detailed anti-inflammatory properties of chlorogenic acid (CGA) and to delineate the possible mode of action. To explore the anti-inflammatory profile, we evaluated the effect of CGA on TNF-alpha expression (in vitro); carrageenan induced rat paw edema and carrageenan induce pleurisy (in vivo). In our studies, CGA significantly inhibited the TNF-alpha expression, paw edema and antioxidant enzymes in livers of rats in pre-treatment schedule but failed to exert any effect when administered 1 h after carrageenan injection. CGA was also found to be safe, as confirmed by the results of acute toxicity studies and MTT assay. CGA also caused reduction in total leucocytes count most probably by inhibiting neutrophils, but could not alter mononuclear cells count in carrageenan induced pleurisy. Inhibition of exudation was evidenced by the less exudate formation in CGA treated animals, which may be due to decrease in vascular permeability which was further confirmed in acetic acid induced vascular permeability model in mice where significant decrease in vascular permeability was observed. CGA was highly effective in reducing the arachidonic acid metabolites, nitric oxide and pro-inflammatory cytokines production in a dose dependent manner and in some conditions effect observed was almost comparable to ibuprofen. Result of the present investigation shows the anti-inflammatory effects of CGS in different models.