Ginsenosides Rb1 and Rg1 Stimulate Melanogenesis in Human Epidermal Melanocytes via PKA/CREB/MITF Signaling.

Mao Lin,Yun-Ying Zhang,Cai-Xia Tu,Bao-Xiang Zhang,Ao-Xue Wang,Ci Zhang,Nan Shen

doi:10.1155/2014/892073

Abstract

Reduced or defective melanin skin pigmentation may cause many hypopigmentation disorders and increase the risk of damage to the skin triggered by UV irradiation. Ginsenosides Rb1 and Rg1 have many molecular targets including the cAMP-response element-binding protein (CREB), which is involved in melanogenesis. This study aimed to investigate the effects of ginsenosides Rb1 and Rg1 on melanogenesis in human melanocytes and their related mechanisms. The effects of Rb1 and Rg1 on cell viability, tyrosinase activity, cellular melanin content and protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF), and activation of CREB in melanocytes were assessed. Results showed that Rb1 or Rg1 significantly increased cellular melanin content and tyrosinase activity in a dose-dependent manner. By contrast, the cell viability of melanocytes remained unchanged. After exposure to Rb1 or Rg1, the protein levels of tyrosinase, MITF, and phosphorylated CREB were significantly increased. Furthermore, pretreatment with the selective PKA inhibitor H-89 significantly blocked the Rb1- or Rg1-induced increase of melanin content. These findings indicated that Rb1 and Rg1 increased melanogenesis and tyrosinase activity in human melanocytes, which was associated with activation of PKA/CREB/MITF signaling. The effects and mechanisms of Rb1 or Rg1 on skin pigmentation deserve further study.

Highlights

The content of melanin in the skin determines the darkness of skin color
We first assessed the effects of ginsenosides Rb1 and Rg1 on cellular melanin content, tyrosinase activity, and cell viability
The results showed that H-89 pretreatment significantly inhibited Rb1or Rg1-induced phosphorylation of cAMP-response elementbinding protein (CREB) and expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (Figures 4(a) and 4(b)) and significantly blocked the increased melanin content that was induced by ginsenoside Rb1 or Rg1 (Figure 4(c))

Summary

Introduction

The content of melanin in the skin determines the darkness of skin color. Reduced melanin content or defective melanin metabolism may cause many hypopigmentation disorders and increase the risk of skin damage induced by UV irradiation. Many research groups are investigating the regulation of skin pigmentation with the goal of developing tanning cosmetics to reduce the risk of skin cancer and cure or prevent hypopigmentation diseases [1]. Melanin is synthesized in melanocytes via an enzymatic cascade with tyrosinase as a key enzyme. Enhanced tyrosinase activity may increase melanin production [2]. The microphthalmia-associated transcription factor (MITF) binds to the M-box within the tyrosinase promoter resulting in upregulation of tyrosinase gene expression [3,4,5].

Objectives

Methods

Results

Conclusion