Hyperpigmentation mechanism of methyl 3,5-di-caffeoylquinate through activation of p38 and MITF induction of tyrosinase.

Abstract

Methyl 3,5-di-caffeoylquinate (3,5-diCQM) has been used for the treatment of various diseases in oriental medicine, but its effect on melanogenesis has not been reported yet. In this study, the molecular mechanism of 3,5-diCQM-induced melanogenesis was investigated. It was found that 3,5-diCQM induced synthesis of melanin pigments in murine B16F10 melanoma cells in a concentration-dependent manner. Treatment of cells with 3,5-diCQM for 48 h increased extracellular and intracellular melanin production and tyrosinase activity. The expressions of tyrosinase, tyrosinase-related protein 1 (TRP1), and TRP2 were up-regulated in a dose-dependent manner 48 h after 3,5-diCQM treatment. Western blot analysis showed that 3,5-diCQM increased the phosphorylation of p38 mitogen-activated protein kinase and cAMP responsive element binding as well as the expression of microphthalmia-associated transcription factor. In addition, 3,5-diCQM-stimulated cAMP production, and 3,5-diCQM-induced tyrosinase activity and melanin synthesis were attenuated by H89, a protein kinase A inhibitor. These results suggested that 3,5-diCQM-mediated activation of the p38 pathway may represent a novel approach for an effective therapy for vitiligo and hair graying.

• Authors: Hyo Jung Kim, Jin Sook Kim, Je-Tae Woo, Ik-Soo Lee, Byung-Yoon Cha
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 47 Issue 7 Pg. 548-56 (Jul 2015) ISSN: 1745-7270 [Electronic] China
• PMID: 26018825 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Chemical References

• Caffeic Acids
• Microphthalmia-Associated Transcription Factor
• Quinic Acid
• Chlorogenic Acid
• 3,4-di-O-caffeoylquinic acid
• Monophenol Monooxygenase
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Caffeic Acids (pharmacology)
• Cell Line, Tumor
• Chlorogenic Acid (analogs & derivatives)
• Enzyme Activation
• Enzyme Induction
• Mice
• Microphthalmia-Associated Transcription Factor (physiology)
• Monophenol Monooxygenase (biosynthesis)
• Pigmentation Disorders (chemically induced)
• Quinic Acid (analogs & derivatives, pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)