Ultraviolet A (UVA) irradiation is suggested to contribute to melanogenesis through promoting cellular oxidative stress and impairing antioxidant defenses. An overproduction of melanin can be associated with melanoma skin cancer and hyperpigmentation. Therefore, developing effective antimelanogenic agents is of importance. Alpinia galanga (AG) and Curcuma aromatica (CA) are traditional medicinal plants widely used for skin problems. Hence, this study investigated the antimelanogenic effects of AG and CA extracts (3.8-30 microg/ml) by assessing tyrosinase activity, tyrosinase mRNA levels, and melanin content in human melanoma cells (G361) exposed to UVA. The roles in protecting against melanogenesis were examined by evaluating their inhibitory effects on UVA-induced cellular oxidative stress and modulation of antioxidant defenses including antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx), and intracellular glutathione (GSH). In addition, possible active compounds accountable for biological activities of the extracts were identified by thin layer chromatography (TLC)-densitometric analysis. Our study demonstrated that UVA (8 J/cm(2)) induced both tyrosinase activity and mRNA levels and UVA (16 J/cm(2))-mediated melanin production were suppressed by the AG or CA extracts at noncytotoxic concentrations. Both extracts were able to protect against UVA-induced cellular oxidant formation and depletion of CAT and GPx activities and GSH content in a dose-dependent manner. Moreover, TLC-densitometric analysis detected the presence of eugenol and curcuminoids in AG and CA, respectively. This is the first report representing promising findings on AG and CA extract-derived antityrosinase properties correlated with their antioxidant potential. Inhibiting cellular oxidative stress and improving antioxidant defenses might be the mechanisms by which the extracts yield the protective effects on UVA-dependent melanogenesis.

Our data showed that 17beta-estradiol increased the release of PGI2 from HUVEC via the induction of COX-2 which was mediated through protein kinase C. The results suggested that COX-2 might have a role in the cardiovascular protective effect of estrogen.

Prostaglandins (PGs) have numerous cardiovascular and inflammatory effects. Cyclooxygenase (COX), which exists as COX-1 and COX-2 isoforms, is the first enzyme in the pathway in which arachidonic acid is converted to PGs. Prostaglandin E2 (PGE2) exerts a variety of biological activities for the maintenance of local homeostasis in the body. Elucidation of PGE2 involvement in the signalling molecules such as COX could lead to potential therapeutic interventions. Here, we have investigated the effects of PGE2 on the induction of COX-2 in human umbilical vein endothelial cells (HUVEC) treated with interleukin-1beta (IL-1beta 1 ng/ml). COX activity was measured by the production of 6-keto-PGF1alpha, PGE2, PGF2alpha and thromboxane B2 (TXB2) in the presence of exogenous arachidonic acids (10 microM for 10 min) using enzyme immunoassay (EIA). COX-1 and COX-2 protein was measured by immunoblotting using specific antibody. Untreated HUVEC contained only COX-1 protein while IL-1beta treated HUVEC contained COX-1 and COX-2 protein. PGE2 (3 microM for 24h) did not affect on COX activity and protein in untreated HUVEC. Interestingly, PGE2 (3 microM for 24h) can inhibit COX-2 protein, but not COX-1 protein, expressed in HUVEC treated with IL-1beta. This inhibition was reversed by coincubation with forskolin (100 microM). The increased COX activity in HUVEC treated with IL-1beta was also inhibited by PGE2 (0.03, 0.3 and 3 microM for 24h) in a dose-dependent manner. Similarly, forskolin (10, 50 or 100 microM) can also reverse the inhibition of PGE2 on increased COX activity in IL-1beta treated HUVEC. The results suggested that (i) PGE2 can initiate negative feedback regulation in the induction of COX-2 elicited by IL-1beta in endothelial cells, (ii) the inhibition of PGE2 on COX-2 protein and activity in IL-1beta treated HUVEC is mediated by cAMP and (iii) the therapeutic use of PGE2 in the condition which COX-2 has been involved may have different roles.