| Rosemary (Rosmarinus officinalis L.) leaves are widely used as food ingredient, and have been focused on their strong antioxidant, anti-inflammatory, and anti-cancer activities. Rosmanol is transformed from carnosol, one of strong antioxidant in rosemary extract, in the presence of oxygen and demonstrated that it has a potential for anti-inflammatiory activities.;Our study consists of two parts: Anti-inflammatory activity of rosmanol on LPS induced iNOS and COX-2 in RAW 264.7 cells and inhibition activity of rosmanol and carnosol on TPA inflammation in mouse ear.;In first study, rosmanol markedly inhibited LPS-stimulated iNOS and COX-2 protein and gene expression, as well as their regulated products, NO and PGE 2. Treatment with rosmanol also reduced translocation of NF-kappaB through preventing degradation and phosphorylation of IkappaB. Western blot analysis showed that rosmanol significantly inhibited translocation and phosphorylation of NF-kappaB and STAT3, and the protein expression of C/EBPbeta and C/EBPdelta. Our results showed that rosmanol downregulates iNOS and COX-2 gene expression by inhibiting the activation of NF-kappaB through interfering with the activation of PI3K/Akt and MAPK signal pathway.;Based on the positive results of in vitro activity of rosmanol and the similarity of chemical structure with carnosol, we designed and performed in vivo study with rosmanol and carnosol. In inhibitory activity of rosmanol and carnosol on TPA-induced persistent inflammation in mouse ear, we examined inhibitory activity of rosmanol and carnosol on production of pro-inflammatory cytokines such as Il-1beta and Il-6. The expression of inflammatory COX-2 and its upstream regulators such as NF-kappaB and IKK-beta, and its product, PGE2 were also examined. A large amount of COX-2 expression and its upstream regulators were detected in LPS induced mouse ear. In rosmanol and carnosol treated group, expression of pro-inflammatory cytokines and PGE2 were decreased markedly. The expression of COX-2 was also reduced, which was resulted from inhibiting up-stream regulators such as NF-kappaB and IKK-beta. In histology of rosmanol and carnosol treated groups their all inflammatory parameters are shown to be much milder condition. Also, there is significant reduced in degree of inflammation index.;Taken together, rosmanol and carnosol, abundant ingredient in rosemary might be a potent anti-inflammatory reagent. |
