Inhibitory effect of p-coumaric acid by Rhodiola sachalinensis on melanin synthesis in B16F10 cells.
Rhodiola has been widely used in traditional Asian medicine. In this study, we tested the hypopigmentation effects of R. sachalinensis and its active compounds including catechin, chlorogenic acid, p-coumaric acid, and p-tyrosol. Results have shown that only p-coumaric acid inhibits melanin synthesis in B16F10 cells. However, p-coumaric acid did not inhibit tyrosinase activity when L-DOPA was used as a substrate. Instead, p-coumaric acid inhibited tyrosinase activity when L-tyrosine was used as a substrate. We further analyzed the changes of cAMP responsive element binding protein (CREB) phosphorylation and tyrosinase gene expression. The results indicate that p-coumaric acid does not affect CREB phosphorylation or tyrosinase protein production. In turn, these findings demonstrate that p-coumaric acid has no effect on the upstream regulation of tyrosinase gene expression, although p-coumaric acid showed a significant inhibitory effect on melanogenesis. Because p-coumaric acid showed different effects on tyrosinase activity according to different substrates, we tested whether tyrosinase can utilize p-coumaric acid as a substrate. Our findings revealed that competitive inhibition occurs between p-coumaric acid and tyrosine. Consequently, this finding could be a primary mechanism for the hypopigmenting action of p-coumaric acid.
Park
So-Hee
SH
Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kim
Dong-Seok
DS
Park
Seo-Hyoung
SH
Shin
Jung-Won
JW
Youn
Sang-Woong
SW
Park
Kyoung-Chan
KC
D015153:Blotting, Western; D002392:Catechin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002726:Chlorogenic Acid / Q000494:pharmacology; D003373:Coumaric Acids / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000378:metabolism; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation; D011422:Propionates; D029771:Rhodiola / Q000737:chemistry*; D014443:Tyrosine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000521:alpha-MSH / Q000494:pharmacology
D003373:Coumaric Acids; D017362:Cyclic AMP Response Element-Binding Protein; D008543:Melanins; D011422:Propionates; C011867:4-hydroxyphenylethanol; D002726:Chlorogenic Acid; D014443:Tyrosine; D007980:Levodopa; D000521:alpha-MSH; D002392:Catechin; D014442:Monophenol Monooxygenase; C495469:p-coumaric acid; D010626:Phenylethyl Alcohol