Depigmenting Effects of <i>Vitex rotundifolia</i> Cone Essential Oil in Melanocytes and Its Chemical Composition

Vitex rotundifolia L.f. (VRL) is a plant belonging to the Verbenaceae family with antipyretic, analgesic, and anti-inflammatory properties, but research on the melanocyte-targeted skin depigmenting-related responses of VRL is lacking. In this study, VRL cone essential oil (VRLCEO) was obtained through steam distillation, and its effects on melanin synthesis and transport-related responses were investigated. Gas chromatography-mass spectrometry analysis identified 15 components from VRLCEO. In all biological activity experiments, VRLCEO was used at noncytotoxic concentrations (≤ 50 µg/mL) to ensure cell viability. VRLCEO inhibited serum-induced cell proliferation of B16BL6 mouse melanoma cells. VRLCEO suppressed tyrosinase enzyme activity and melanin synthesis in B16BL6 melanoma cells induced by α-MSH. VRLCEO also reduced the expression of MITF, tyrosinase, and TRP-2 proteins in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16BL6 cells, but did not affect TRP-1 protein expression. Moreover, it increased the p38 MAPK and ERK1/2 phosphorylation levels in α-MSH-exposed B16BL6 cells, but not the JNK phosphorylation level. Furthermore, VRLCEO decreased α-MSH-upregulated Rab27a and melanophilin expression in B16BL6 cells. Therefore, VRLCEO may exert an anti-pigmentation effect by inhibiting melanin production and transfer in melanocytes. Accordingly, VRLCEO may be a natural material for the development of skin whitening agents.