Tanshinone IIA, a melanogenic ingredient basis of Salvia miltiorrhiza Bunge

Background: The roots of Salvia miltiorrhiza Bunge ( Lamiaceae ) have been often used to treat vitiligo in clinical for many years. However, the main ingredient basis of efficacy has not been known. Objectives: We investigated whether the two main constituents of S. miltiorrhiza , major hydrophobic compound tanshinone IIA (Tan IIA) and the major hydrophilic compound salvianolic acid B (Sal B), had the same melanogenic activity. Methods: To testify the potential roles of Tan IIA and Sal B in pigmentation, tyrosinase (Tyr) activity, melanin synthesis ability, and the molecular mechanisms stimulating melanin production were determined in B16F10 melanoma cells. Results: Tan IIA promoted melanogenesis and enhanced Tyr activity at its maximum concentration (10 μM), whereas that of Sal B had no effect. Furthermore, the color of cell pellets and morphological observation of B16F10 cells were visibly darkened. Regarding molecular mechanisms, Western blot results showed that Tan IIA (1, 3, and 10 μM) dose dependently increased the level of phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase MAPK, respectively. However, it decreased phosphorylation in extracellular signal-regulated protein kinase 1/2 MAPK signaling. Meanwhile, Tan IIA promoted the expression of microphthalmia-associated transcription factor and Tyr. Conclusion: Tan IIA might be a melanogenic ingredient basis of S. miltiorrhiza to increase the Tyr activity by activating the upstream MAPK signaling pathways, thereby contributing to pigmentary processing.