Piperlonguminine from Piper longum with inhibitory effects on alpha-melanocyte-stimulating hormone-induced melanogenesis in melanoma B16 cells

Skin hyperpigmentations such as melasma, freckles and senile lentigines can be subjectively treated by depigmenting agents. In our ongoing study to find melanogenesis inhibitors from natural sources, Piper longum L (fruits, Piperaceae) was discovered to have an inhibitory effect on alpha-melanocyte- stimulating hormone (α-MSH)-induced melanogenesis in melanoma B16 cells. Piperlonguminine has been identified as the melanogenesis inhibitor from P. longum by activity-guided extraction and isolation. The compound showed dose-dependent inhibitory effects with 85.1 ± 4.9% inhibition at 25 μM, 62.1 ± 6.1 % at 12.5 μM, 36.4 ± 4.6% at 6.3 μM and 18.4 ± 5.1 % at 3.1 μM on α-MSH-induced melanogenesis, showing an IC₅₀ value of 9.6 μM. As a positive control, kojic acid exhibited an IC₅₀ value of 44.6 μM on the melanogenesis. As to the mode of action, piperlonguminine showed an inhibitory effect on α-MSH-induced tyrosinase synthesis, documented by Western immunoblot analysis. However, piperlonguminine did not show an inhibitory effect on tyrosinase activity or a direct depigmenting effect of melanin.