title: Novel inhibitory effect of the antidiabetic drug voglibose on melanogenesis.
abstract: Overproduction of melanin can lead to medical disorders such as postinflammatory melanoderma and melasma. Therefore, developing antimelanogenic agents is important for both medical and cosmetic purposes. In this report, we demonstrated for the first time that the antidiabetic drug voglibose is a potent antimelanogenic agent. Voglibose is a representative antidiabetic drug possessing inhibitory activity towards human α-glucosidase; it blocked the proper N-glycan modification of tyrosinase, resulting in a dramatic reduction of the tyrosinase protein level by altering its stability and subsequently decreasing melanin production. Acarbose, another antihyperglycaemic drug that has a lower inhibitory effect on human intracellular α-glucosidase compared with voglibose, did not cause any changes in either the N-glycan modification of tyrosinase or the tyrosinase protein level, indicating that voglibose was the most efficient antimelanogenic agent among the widely used antihyperglycaemic agents. Considering that voglibose was originally selected from the valiolamine derivatives in a screen for an oral antidiabetic drug with a strong inhibitory activity towards intestinal α-glucosidase and low cell permeability, we propose an alternative strategy for screening compounds from valiolamine derivatives that show high inhibitory activity towards human intracellular α-glucosidases and high cell permeability, with the goal of obtaining antimelanogenic agents that are effective inside the cells.
authors.affiliation: Bioscience Research Institute, AmorePacific Corporation R&D Center, Yongin, Korea.
authors.forename: Bum-Ho
authors.initials: BH
authors.lastname: Bin
authors.forename: Juyeon
authors.initials: J
authors.lastname: Seo
authors.forename: Seung Ha
authors.initials: SH
authors.lastname: Yang
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Lee
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Choi
authors.forename: Kyu-Han
authors.initials: KH
authors.lastname: Kim
authors.forename: Eun-Gyung
authors.initials: EG
authors.lastname: Cho
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Lee
mesh_terms: D020909:Acarbose / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007249:Inflammation; D007294:Inositol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008361:Mannosidases; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000166:cytology* / Q000187:drug effects*; D046529:Microscopy, Electron, Transmission; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010539:Permeability; D011134:Polysaccharides / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects; D050111:Imino Sugars
chemical_list: D020909:Acarbose; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007294:Inositol; D008361:Mannosidases; D008543:Melanins; D014442:Monophenol Monooxygenase; D011134:Polysaccharides; C043270:valiolamine; D050111:Imino Sugars; C102817:voglibose
keywords: N-glycan processing; antidiabetic drug; antihyperglycaemic agent; melanin; melanocyte; melanogenesis; valiolamine; voglibose; α-glucosidase