Influence of Gungguitang-gamibang on the Regulation of Melanogenesis through JNK Signaling Pathway in B16 Melanoma Cells

Gunggui-tang has been used for the therapy of blood disorders in Hangbang medicine for long time. Also, Glycyrrhiza uralensis has been used for deficientblood patterns with an irregular pulse or palpitations, coughing and wheezing, and heat or cold in the lungs. Melanogenesis is a physiological process resulting in the synthesis of melanin pigments. We investigated whether the water extract of Gunggui-tang plus G. uralensis inhibited melanogenesis in B16 melanoma cells. Because the molecular events connecting the regulation in tyrosinase activity remain to be elucidated, we also aimed to determine whether Gunggui-tang gamibang(GTG) affects tyrosinase at the gene activation level in the cells. First, we showed that GTG inhibited the tyrosinase promoter activity and further, down-regulated the tyrosinase protein activity in ${\alpha}-melanocyte-stimulating$ hormone $({\alpha}-MSH)-treated$ B16 melanoma cells. GTG also resulted in a decrease of melanin content in MSH-induced melanogenesis, indicating that GTG may be a useful drug in studying the regulation of melanogenesis. The pretreatment of GTG significantly prevented phosphotransferase activity of c-Jun N-terminal kinase (JNK1) and transcriptional activation of activating protein-1 (AP-1) in MSH-treated B16 melanoma cells. These findings indicate that GTG inhibits melanogenesis of B16 melanoma cells via suppression of phosphotransferase activity of JNK1 and transcriptional activation of AP-1.