Xanthones with pancreatic lipase inhibitory activity from the pericarps of Garcinia mangostana L. (Guttiferae)

Abstract

Bioactivity-guided isolation of natural compounds from the pericarps of Garcinia mangostana, using a pancreatic lipase assay, led to the identification of 13 xanthones including α-mangostin (1), β-mangostin (2), γ-mangostin (3), 1-isomangostin (4), gartanin (5), garcinone D (6), 9-hydroxycalabaxanthone (7), smeathxanthone A (8), tovophyllin A (9), 8- deoxygartanin (10), mangostanin (11), calocalabaxanthone (12), and 1,7-dihydroxy-3-methoxy-2-(3-methylbut-2-enyl) xanthen-9-one (13). The inhibitory activities of the isolated xanthones against pancreatic lipase were evaluated and α-mangostin (1) was found to possess the most potent inhibitory activity (IC50 5.0 μM) in a non-competitive manner, compared with the positive control, orlistat (IC50 3.9 μM). Practical applications: Pancreatic lipase is a key enzyme in lipid absorption. A total of 13 compounds were isolated from the pericarps of G. mangostana. Their structures were characterized by HRESI-MS, and 1D and 2D-NMR spectroscopic data. Our results show that all the isolates exhibited inhibitory activity against pancreatic lipase. Of the active xanthones, α-mangostin displayed the most potent lipase inhibition, with an IC50 value of 5.0 μM. Furthermore, kinetic analysis of α-mangostin was carried out. In the Lineweaver？Burk plot, the apparent Vmax values in the presence of 1, 2, 4, and 10 μM α-mangostin were decreased compared with those without α-mangostin, whereas the Km values of 4-MU oleate with and without α-mangostin were both close to 3.22 μM. Finally, it is evident that xanthone derivatives isolated from G. mangostana possess pancreatic lipase inhibitory activities. A total of 13 compounds are isolated from the pericarps of Garcinia mangostana. α-Mangostin is found to possess the most potent lipase inhibitory activity.