title: Quercetin-3-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside suppresses melanin synthesis by augmenting p38 MAPK and CREB signaling pathways and subsequent cAMP down-regulation in murine melanoma cells.
abstract: In this study, the effect of purified quercetin-3-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosid (QCGG) on melanogenesis was investigated. QCGG was isolated from the calyx of a traditional Korean medicinal herb, Persimmon (Diospyros kaki). The hypopigmentation effects of QCGG were determined by examination of cellular melanin contents, tyrosinase activity assay, cAMP assay, and Western blotting of α-MSH-stimulated B16F10 mouse melanoma cells. Our results showed that QCGG inhibited both melanin synthesis and tyrosinase activity in a concentration-dependent manner as well as significantly reduced the expression of melanogenic proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1, tyrosinase-related protein-2, and tyrosinase. Moreover, QCGG inhibited intracellular cAMP levels, cAMP response element-binding protein (CREB), and p38 MAPK expression in α-MSH-stimulated B16F10 cells. Taken together, the suppressive effects of QCGG on melanogenesis may involve down-regulation of MITF and its downstream signaling pathway via phosphorylation of p38 MAPK and CREB along with reduced cAMP levels. These results indicate that QCGG reduced melanin synthesis by reducing expression of tyrosine and tyrosine-related proteins via extracellular signal-related protein kinase (ERK) activation, followed by down-regulation of CREB, p38, and MITF.
authors.affiliation: Department of Cosmeceutical Science, Daegu Hanny University, Gyeongbuk 712-715, Republic of Korea.
authors.forename: Hyun Gug
authors.initials: HG
authors.lastname: Jung
authors.affiliation: Department of Pharmacognosy, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors.forename: Han Hyuk
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook, 712-714, Republic of Korea.
authors.forename: Souren
authors.initials: S
authors.lastname: Paul
authors.affiliation: Department of Cosmeceutical Science, Daegu Hanny University, Gyeongbuk 712-715, Republic of Korea.
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Cosmeceutical Science, Daegu Hanny University, Gyeongbuk 712-715, Republic of Korea.
authors.forename: Yong Hun
authors.initials: YH
authors.lastname: Cho
authors.affiliation: Department of Cosmeceutical Science, Daegu Hanny University, Gyeongbuk 712-715, Republic of Korea ; Institute of Technology, Herbnoori, Daegu 702-062, Republic of Korea.
authors.forename: Hyeon Jeong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Cosmeceutical Science, Daegu Hanny University, Gyeongbuk 712-715, Republic of Korea.
authors.forename: Jae Myo
authors.initials: JM
authors.lastname: Yu
authors.affiliation: Department of Cosmeceutical Science, Daegu Hanny University, Gyeongbuk 712-715, Republic of Korea.
authors.forename: Eun Su
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Cosmeceutical Science, Daegu Hanny University, Gyeongbuk 712-715, Republic of Korea.
authors.forename: Bong Jeun
authors.initials: BJ
authors.lastname: An
authors.affiliation: Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook, 712-714, Republic of Korea.
authors.forename: Sun Chul
authors.initials: SC
authors.lastname: Kang
authors.affiliation: Department of Food and Nutrition, Eulji University, 553, Sanseong-Dero, Sugeong-Gu, Seongnam-Si, Gyeong-Do 461-713, Republic of Korea.
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Bang
keywords: CREB; Melanogenesis; Persimmon calyx; TRPs; cAMP; p38 MAPK