The Development of Sugar-Based Anti-Melanogenic Agents.
The regulation of melanin production is important for managing skin darkness and hyperpigmentary disorders. Numerous anti-melanogenic agents that target tyrosinase activity/stability, melanosome maturation/transfer, or melanogenesis-related signaling pathways have been developed. As a rate-limiting enzyme in melanogenesis, tyrosinase has been the most attractive target, but tyrosinase-targeted treatments still pose serious potential risks, indicating the necessity of developing lower-risk anti-melanogenic agents. Sugars are ubiquitous natural compounds found in humans and other organisms. Here, we review the recent advances in research on the roles of sugars and sugar-related agents in melanogenesis and in the development of sugar-based anti-melanogenic agents. The proposed mechanisms of action of these agents include: (a) (natural sugars) disturbing proper melanosome maturation by inducing osmotic stress and inhibiting the PI3 kinase pathway and (b) (sugar derivatives) inhibiting tyrosinase maturation by blocking N-glycosylation. Finally, we propose an alternative strategy for developing anti-melanogenic sugars that theoretically reduce melanosomal pH by inhibiting a sucrose transporter and reduce tyrosinase activity by inhibiting copper incorporation into an active site. These studies provide evidence of the utility of sugar-based anti-melanogenic agents in managing skin darkness and curing pigmentary disorders and suggest a future direction for the development of physiologically favorable anti-melanogenic agents.
AmorePacific Corporation Research &amp; Deveolopment Center, Yongin, Gyeonggi-do 446-729, Korea. bbh82429@amorepacific.com.
Bum-Ho
BH
Bin
AmorePacific Corporation Research &amp; Deveolopment Center, Yongin, Gyeonggi-do 446-729, Korea. sungtae7@amorepacific.com.
Sung Tae
ST
Kim
Department of Chemical Engineering, POSTECH, Pohang 790-784, Korea. bynjh007@postech.ac.kr.
Jinhyuk
J
Bhin
AmorePacific Corporation Research &amp; Deveolopment Center, Yongin, Gyeonggi-do 446-729, Korea. trlee@amorepacific.com.
Tae Ryong
TR
Lee
AmorePacific Corporation Research &amp; Deveolopment Center, Yongin, Gyeonggi-do 446-729, Korea. egcho@amorepacific.com.
Eun-Gyung
EG
Cho
D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D002241:Carbohydrates / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects*
D000951:Antigens, Neoplasm; D002241:Carbohydrates; D008543:Melanins; D026901:Membrane Transport Proteins; C510061:SLC45A2 protein, human
anti-melanogenic agent; melanin; osmotic stress; stress N-glycosylation; sugar