A chemical compound from fruit extract of Juglans mandshurica inhibits melanogenesis through p-ERK-associated MITF degradation

Background: Trials for regulation of abnormal hyperpigmentation from the use of natural products have been going on for years. Leaf and root extracts from Juglans mandshurica are reported to function as antioxidants and to suppress allergic dermatitis. However, studies evaluating its fruit extract and the chemical compounds from the fruit extract are lacking in dermatology fields, including melanogenesis. Purpose: The aim of this study is to understand the effect of the fruit extract from J. mandshurica on pigmentation and to search for specific chemical compounds that affect melanogenesis. Methods: After screening out any anti-melanotic effects of the fruit extract from J. mandshurica in B16F10 melanoma cells, three major phenolic compounds isolated from the fruit extract were tested by western blot analysis for expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. Their effect on B16F10 melanoma cells with regard to melanogenesis was also confirmed in primary human epidermal melanocytes (PHEMs). PD98059 was tested to observe the compounds’ signaling role in the extracellular signal-regulated protein kinase (ERK)-pathway. Results: Fruit extract from J. mandshurica showed anti-melanotic effects in B16F10 melanoma cells. After chemical compounds were isolated from the fruit extracts, three phenolic compounds were evaluated for anti-melanotic effects. 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol (compound 1) showed the highest suppression effect among the three compounds. In B16F10 melanoma cells and PHEMs, reduced melanin contents were observed after treatment with the compound (1). Experiments using a blocker of ERK showed that the inhibitory effect of the compound (1) on melanogenesis was dependent on ERK-associated MITF degradation. Conclusion: A chemical constituent of Juglans mandshurica Maxim. induces an inhibitory mechanism to melanogenesis. It has the potential to become a whitening agent in the medical field, though this requires further clinical investigation.