Antiangiogenic Activity of Mangostins Isolated from Thailand Stingless Bee Propolis

Abstract

Background/Objective Propolis, a resinous substance collected by honeybees from origin plants to protect their beehive, has been reported to have various biological activities and gained popularity as an alternative medicine in recent years. We have previously reported the plant origin, the chemical composition and some biological activities of native Thailand stingless bee propolis. In this study, we further elucidated its active components and their mode of action. Methods/Results Among nine prenylated xanthones isolated from this propolis, α-mangostin and γ-mangostin were shown to strongly inhibit tube formation of human umbilical vein endothelial cells (HUVECs), an indication of antiangiogenic activity in vitro. Further investigation of their effects at a molecular level revealed that both mangostins inactivated extracellular signal-regulated kinase 1/2 (ERK1/2) and activated p38 in tube-forming HUVECs in a concentration-dependent manner. Taken together, the two mangostins were shown to inhibit angiogenesis in vitro by inactivating angiogenic signal ERK1/2 and activating stress signal p38. Detailed comparison revealed that α-mangostin seemed to have a slightly stronger effect than γ-mangostin in these experiments. Combined with the fact that being the most abundant component among the nine prenylated xanthones tested, α-mangostin might be responsible for the antiangiogenic activity of this Thailand stingless bee propolis. Conclusion These results indicate that α-mangostin isolated from Thailand stingless bee propolis may be a good candidate for future applications in the prevention of angiogenesis-related diseases.