Soyasaponin-I Attenuates Melanogenesis through Activation of ERK and Suppression of PKA/CREB Signaling Pathways

Soyasaponin-I (SS-I), a sialyltransferase inhibitor naturally found in soybeans, has antioxidant, anticarcinogenic, and hepatoprotective properties. In this study, we explored the possibility to use SS-I as an antimelanogenic agent for the treatment of skin hyperpigmentation disorders. When melanoma cell lines, MNT-1 and B16F10, were treated with SS-I, significant suppression of both α-2,3 and α-2,6 sialylations was observed by using lectin fluorescence staining with sialic acid-binding lectins-<i>Sambucus nigra</i> agglutinin (SNA) and <i>Maackia amurensis</i> lectin-II (MAL-II). SS-I significantly attenuated the α-MSH-induced melanogenesis of MNT-1 and B16F10 cells without a cytotoxic effect. SS-I could activate ERK and suppress the PKA/CREB signaling pathways of melanoma cells. Moreover, SS-I treatment caused significant downregulation of the expression of melanosome-related proteins; tyrosinase-related protein 1 (TRP1), TRP2, and premelanosome protein (PMEL) and the melanogenic-related transcription factor microphthalmia-associated transcription factor (MITF). Consequently, the expression of tyrosinase-the key enzyme regulating melanin production-was significantly suppressed after SS-I treatment. These results suggest the role of sialylation in melanogenesis and the possibility of using SS-I as an alternative antimelanogenic agent. In conclusion, we have demonstrated the antimelanogenic effect of SS-I, an active compound produced in soybeans. SS-I can be an antimelanogenic agent in cosmetic products for the treatment of hyperpigmentation disorders.