Polymethoxyflavones from Kaempferia parviflora stimulate melanogenesis by blocking the TPC2 channel

Kaempferia parviflora, well-known as Thai ginseng (Krachaidum), has been used as a medicinal plant and food source for centuries. Its rhizome contains several flavonoids, particularly poly-O-methylated flavones (also known as polymethoxyflavones). We previously found that K. parviflora extract had a strong stimulatory effect on melanogenesis in B16F10 mouse melanoma cells. The aim of this study was to investigate the melanogenic stimulation exerted by various O-methylated flavonoids from K. parviflora in human melanoma cells and elucidate the mechanism of action of the most active compound. MNT-1 cells were used to screen for the most potent O-methylated flavonoid, and its effects on some key steps in melanin biosynthesis would subsequently be investigated. The poly-O-methylated flavone 3,5,7,3',4'-pentamethoxyflavone (PMF) exhibited the strongest melanogenesis-stimulating activity among the 13 O-methylated flavones isolated from K. parviflora. It was shown to enhance tyrosinase (TYR) activity by upregulating the levels of TYR and TYR-related protein 1 (TRP-1) via its inhibitory effect on two-pore channel 2 (TPC2). In conclusion, poly-O-methylated flavones, especially PMF, were suggested as a potential group of flavonoids that could stimulate melanin production by inhibiting the activity of the TPC2 channel, leading to increased TYR and TRP-1 activities.