Next Article in Journal
Next Article in Special Issue
Previous Article in Journal
Previous Article in Special Issue
Int. J. Mol. Sci. 2014, 15(5), 8293-8315; doi:10.3390/ijms15058293
Review

Inhibitors of Intracellular Signaling Pathways that Lead to Stimulated Epidermal Pigmentation: Perspective of Anti-Pigmenting Agents

1,*  and 2
Received: 14 March 2014; in revised form: 17 April 2014 / Accepted: 29 April 2014 / Published: 12 May 2014
View Full-Text   |   Download PDF [5096 KB, uploaded 19 June 2014]
Abstract: Few anti-pigmenting agents have been designed and developed according to their known hyperpigmentation mechanisms and corresponding intracellular signaling cascades. Most anti-pigmenting agents developed so far are mechanistically involved in the interruption of constitutional melanogenic mechanisms by which skin color is maintained at a normal and unstimulated level. Thus, owing to the difficulty of confining topical application to a specific hyperpigmented skin area, potent anti-pigmenting agents capable of attenuating the natural unstimulated pigmentation process have the risk of leading to hypopigmentation. Since intracellular signaling pathways within melanocytes do not function substantially in maintaining normal skin color and are activated only by environmental stimuli such as UV radiation, specifically down-regulating the activation of melanogenesis to the constitutive level would be an appropriate strategy to develop new potent anti-pigmenting agents with a low risk of hypopigmentation. In this article, we review the hyperpigmentation mechanisms and intracellular signaling pathways that lead to the stimulation of melanogenesis. We also discuss a screening and evaluation system to select candidates for new anti-melanogenic substances by focusing on inhibitors of endothelin-1 or stem cell factor-triggered intracellular signaling cascades. From this viewpoint, we show that extracts of the herbs Withania somnifera and Melia toosendan and the natural chemicals Withaferin A and Astaxanthin are new candidates for potent anti-pigmenting substances that avoid the risk of hypopigmentation.
Keywords: intracellular signaling pathway; signaling inhibitors; endothelin; stem cell factor; ultraviolet B-melanosis; solar lentigo; melasma intracellular signaling pathway; signaling inhibitors; endothelin; stem cell factor; ultraviolet B-melanosis; solar lentigo; melasma
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Imokawa, G.; Ishida, K. Inhibitors of Intracellular Signaling Pathways that Lead to Stimulated Epidermal Pigmentation: Perspective of Anti-Pigmenting Agents. Int. J. Mol. Sci. 2014, 15, 8293-8315.

AMA Style

Imokawa G, Ishida K. Inhibitors of Intracellular Signaling Pathways that Lead to Stimulated Epidermal Pigmentation: Perspective of Anti-Pigmenting Agents. International Journal of Molecular Sciences. 2014; 15(5):8293-8315.

Chicago/Turabian Style

Imokawa, Genji; Ishida, Koichi. 2014. "Inhibitors of Intracellular Signaling Pathways that Lead to Stimulated Epidermal Pigmentation: Perspective of Anti-Pigmenting Agents." Int. J. Mol. Sci. 15, no. 5: 8293-8315.



Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert