Tyrosinase (TYR) catalyzes rate-limiting steps of melanogenesis and thus its inhibitors are potentially useful as hypopigmenting agents. Recently, p-coumaric acid (p-CA) has been suggested to interfere with the pro-melanogenic actions of tyrosine due to its structural similarity with tyrosine (An SM et al., Br J Dermatol 2008. 159: 292). In this study, we compared the inhibitory effects of p-CA and two other well known TYR inhibitors used in cosmetics--arbutin and kojic acid--on the catalytic activities of mushroom, murine and human TYRs in vitro, using tyrosine and 3,4-dihydroxyphenylalanine (DOPA) as substrates. The results showed that p-CA is a weaker inhibitor of mushroom TYR but much stronger inhibitor of human or murine TYR in comparison with kojic acid and arbutin. In addition, p-CA inhibited human TYR at much lower concentrations than those required for the inhibition of murine or mushroom TYRs. Enzyme kinetics analysis indicated that p-CA is a mixed type (for tyrosine) or competitive inhibitor (for DOPA) of human TYR. Potent antimelanogenic effects of p-CA were observed in human epidermal melanocytes exposed to UVB. The present study demonstrated that p-CA is a potent and selective inhibitor of human TYR and is potentially useful as a hypopigmenting agent.

Resveratrol has a variety of bioactivities that include its anti-melanogenic effects, but its use in cosmetics has been challenging partly because of its chemical instability. Resveratryl triacetate (RTA) is a prodrug that can enhance stability. The purpose of this study was to examine the skin safety and whitening effects of RTA in human subjects. The primary skin irritation potentials of RTA and resveratrol were tested at 0.1 and 0.5 % on human subjects. Resveratrol at a concentration of 0.5 % induced weak skin irritation, whereas RTA did not induce any skin responses. The skin-whitening efficacy of a cosmetic formulation containing 0.4 % RTA was evaluated in two different test models. In the artificial tanning model, the test product and the control product were applied twice daily to the skin of the forearms of 22 human subjects after pigmentation induction by ultraviolet irradiation. Applying the test and the control products to the artificial tanning model for 8 weeks increased the individual topology angles (ITA°) by 17.06 and 13.81 %, respectively, a difference that was statistically significant (p < 0.05). In the hyperpigmentation model, the test product and the control product were applied twice daily to the faces of 21 human subjects. The averaged intensity of the hyperpigmented spots decreased by 2.67 % in the test group and 1.46 % in the control group, a difference that was statistically significant (p < 0.05). Therefore, RTA incorporated into cosmetic formulations can whiten human skin without inducing skin irritation.

Alcohol drinking during pregnancy results in abnormal fetal development, including fetal alcohol syndrome (FAS) in humans and experimental animals. FAS is characterized by two major effects, including central nervous system (CNS) dysfunction and multiple anomalies recognizable mainly as a typical face. However, the mechanisms of alcohol-induced embryotoxicity have not been clearly demonstrated. The aim of the present study was to investigate the possible mechanisms underlying ethanol-induced FAS in the developing embryo. First, ethanol-induced developmental abnormalities were investigated in vitro. Postimplantation embryos at gestation day (GD) 9.5 were cultured for 48 h and observed for morphological changes. Ethanol-mediated changes in proteins regulated apoptosis (p53 and bcl-2), antioxidant (vitamin E and catalase) activities, generation of reactive oxygen species (ROS), and oxidative DNA damage shown as 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured in embryonic midbrain cells. Alcohol or acetaldehyde significantly induced cytotoxicity in cultured rat embryonic midbrain cells. The levels of p53, bcl-2, and 8-OHdG were concomitantly changed by alcohol and acetaldehyde treatment in midbrain cells. Injured cells induced by ROS were increased by alcohol or acetaldehyde treatment in midbrain cells. Cotreatment with alcohol or acetaldehyde and catalase decreased cytotoxicity in midbrain cells. In postimplantation embryo culture, alcohol or acetaldehyde-treated embryos showed retardation of embryonic growth and development in a concentration-dependent manner. These results indicate that alcohol and its metabolite acetaldehyde induce fetal developmental abnormalities by disrupting cellular differentiation and growth. Data demonstrate that some antioxidants can partially protect against the alcohol-induced embryonic developmental toxicity.

Litter size is among the most important traits in swine breeding. However, information on the genetics of litter size in pigs is lacking. In this study, we identified single nucleotide polymorphisms (SNPs) in the insulin-like growth factor binding protein 2 and 3 (IGFBP2 and IGFBP3) genes in Berkshire pigs and analyzed their association with litter size traits. The IGFBP2 SNP was located on chromosome 15 intron 2 (455, A > T) and the IGFBP3 SNP was on chromosome 18 intron 2 (53, A > G). The AT type of IGFBP2 and the GG type of IGFBP3 had the highest values for all litter size traits including total number born (TNB), number of pigs born alive, and breeding value according to TNB. Homozygous GG pigs expressed higher levels of IGFBP3 mRNA in the endometrium than pigs of other genotypes, and a positive correlation was observed between litter size traits and IGFBP3 but not IGFBP2 expression level. These results suggest that SNPs in the IGFBP2 and the IGFBP3 gene are useful biomarkers for increasing the reproductive productivity of Berkshire pigs.