title: The Glutathione Derivative, GSH Monoethyl Ester, May Effectively Whiten Skin but GSH Does Not.
abstract: Glutathione in its reduced form (GSH) is an antioxidant and also is involved in pheomelanin formation. Thus, it has been long believed that GSH has a skin whitening effect. However, its actual or direct effect is unproven. We evaluated the anti-melanogenic effects of GSH and its derivatives in vitro. We examined change of melanogenesis and its related proteins by GSH itself and its derivatives, including GSH monoethyl ester (GSH-MEE), GSH diethyl ester (GSH-DEE) and GSH monoisopropyl ester (GSH-MIPE) in Melan-A cells, Mel-Ab cells, and B16F10 cells. GSH and GSH-MEE did not display cytotoxic activity, but GSH-MIPE and GSH-DEE did. Intriguingly, GSH itself had no inhibitory effect on melanin production or intracellular tyrosinase activity. Rather, it was GSH-MEE and GSH-MIPE that profoundly reduced the amount of melanin and intracellular tyrosinase activity. Thus, GSH-MEE was selected as a suitable candidate skin-whitening agent and it did not alter melanogenesis-associated proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, but it did increase the amount of suggested pheomelanin and suggested pheomelanin/eumelanin ratio. GSH-MEE was effective for anti-melanogenesis, whereas GSH itself was not. GSH-MEE could be developed as a safe and efficient agent for the treatment of hyperpigmentation skin disorders.
authors.affiliation: Department of Dermatology, College of Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul 07441, Korea. victoryby@naver.com.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Chung
authors.affiliation: Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. libesora@gmail.com.
authors.forename: So Ra
authors.initials: SR
authors.lastname: Choi
authors.affiliation: Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. ikjun.moon@gmail.com.
authors.forename: Ik Jun
authors.initials: IJ
authors.lastname: Moon
authors.affiliation: Department of Dermatology, College of Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul 07441, Korea. dermap@hanmail.net.
authors.forename: Chun Wook
authors.initials: CW
authors.lastname: Park
authors.affiliation: Department of Pharmacology, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. kimyh@amc.seoul.kr.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. csesnumd@gmail.com.
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Chang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D006801:Humans; D008543:Melanins / Q000032:analysis; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D012867:Skin / Q000378:metabolism*; D013053:Spectrophotometry
chemical_list: D008543:Melanins; C042431:S-ethyl glutathione; D005978:Glutathione
keywords: glutathione derivatives; glutathione monoethyl ester; melanogenesis; pheomelanin