Skin protective effect of guava leaves against UV-induced melanogenesis via inhibition of ORAI1 channel and tyrosinase activity

Ultraviolet (UV) irradiation is a major environmental factor affecting photoageing, which is characterized by skin wrinkle formation and hyperpigmentation. Although many factors are involved in the photoageing process, UV irradiation is thought to play a major role in melanogenesis. Tyrosinase is the key enzyme in melanin synthesis; therefore, many whitening agents target tyrosinase through various mechanisms, such as direct interference of tyrosinase catalytic activity or inhibition of tyrosinase mRNA expression. Furthermore, the highly selective calcium channel ORAI1 has been shown to be associated with UV-induced melanogenesis. Thus, ORAI1 antagonists may have applications in the prevention of melanogenesis. Here, we aimed to identify the anti-melanogenesis agents from methanolic extract of guava leaves (Psidium guajava) that can inhibit tyrosinase and ORAI1 channel. The n-butanol (47.47%+/- 7.503% inhibition at 10 mu g/mL) and hexane (57.88%+/- 7.09% inhibition at 10 mu g/mL) fractions were found to inhibit ORAI1 channel activity. In addition, both fractions showed effective tyrosinase inhibitory activity (68.3%+/- 0.50% and 56.9%+/- 1.53% inhibition, respectively). We also confirmed that the hexane fraction decreased the melanin content induced by UVB irradiation and the ET-1-induced melanogenesis in murine B16F10 melanoma cells. These results suggest that the leaves of P. guajava can be used to protect against direct and indirect UV-induced melanogenesis.