Effect of α-mangostin on Enhanced Transdermal Bioavailability of Gartanin via Efflux Transporters

Mangosteen (Garcinia mangostana L) is a tropical evergreen tree growing in Southeast Asia and has been used as traditional medicine treatment for skin wounds and infection. The pericarp crude extract can be isolated to fifty xanthone compounds, α-, β and γ-mangostins, gartanin etc. This study aimed to characterize and compare the transdermal transport of α-mangostin and gartanin when used alone and co-administered in human epidermal keratinocyte cells, neonatal (HEKn cells). The concentrations of the compounds were determined of by LC-MS/MS. In the absorptive direction, gartanin could not be detected during the entire 8 hour. Moreover, apparent permeability coefficient in secretory direction (Papp, B-A) was significantly higher than that of absorptive direction (Papp, A-B) but not found in α-mangostin. The results showed that after incubating the HEKn cells with rotenone, Papp, A-B of gartanin was significantly increased. In contrast, Papp, A-B of α-mangostin with and without rotenone was unchanged. For the mixture of gartanin and α-mangostin, α-mangostin had the similar inhibitory effect to the uptake and secretion of gartanin to the effect of rotenone. These indicated that the effect of efflux transporter of gartanin could be inhibited by α-mangostin and the permeability of gartanin in absorptive direction was achieved with co-administration of α-mangostin at high concentration. It is postulated that alpha-mangostin may act as a natural enhancer to improve the bioavailability of gartanin. The synergistic effect of the co-existing of the compounds in the natural extract may be important for therapy.