p-coumaric acid not only inhibits human tyrosinase activity in vitro but also melanogenesis in cells exposed to UVB.
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.
An
Sang Mi
SM
Department of Molecular Medicine and Cell and Matrix Research Institute, BK21 Medical Education Program for Human Resources, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Koh
Jae-Sook
JS
Boo
Yong Chool
YC
D000363:Agaricales / Q000201:enzymology; D000818:Animals; D001104:Arbutin / Q000494:pharmacology; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D000078404:Epidermal Cells; D006801:Humans; D008544:Melanocytes / Q000187:drug effects* / Q000201:enzymology; D008546:Melanoma, Experimental; D051379:Mice; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010858:Pigmentation / Q000187:drug effects; D011422:Propionates; D011753:Pyrones / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D014466:Ultraviolet Rays
D003373:Coumaric Acids; D011422:Propionates; D011753:Pyrones; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; C011890:kojic acid; D001104:Arbutin; D014442:Monophenol Monooxygenase; C495469:p-coumaric acid