Bioactive monoterpene glycosides conjugated with gallic acid from the leaves of Eucalyptus globulus

Abstract

Two monoterpene glycosides, conjugated with gallic acid [globulusin A ( 1) and B ( 2)], together with four known compounds, cypellocarpin A ( 3), eucaglobulin ( 4), cuniloside ( 5) and (1 S, 2 S, 4 R)- trans-2-hydroxy-1,8-cineole β- d-glucopyranoside ( 6), were isolated from hot-water extracts of the leaves of Eucalyptus globulus. The structures of compounds 1 and 2 were determined by 1D, 2D NMR and MS spectroscopic analyses. The absolute stereochemistry of 1 was determined by correlating the spectroscopic data with those of synthetic compound 6 with a known configuration. Globulusin A ( 1) and B ( 2), cypellocarpin A ( 3) and eucaglobulin ( 4), scavenged DPPH free radicals and globulusin A ( 1) showed a higher antioxidant activity than the other tested compounds, with an IC 50 of 3.8 μM. Globulusin A ( 1) and eucaglobulin ( 4) concentration-dependently suppressed inflammatory cytokine production, tumor-necrosis factor-α and interleukin-1β in cultured human myeloma THP-1 cells co-stimulated with phorbol myristate acetate. These compounds also inhibited melanogenesis in cultured murine melanoma B16F1 cells, without any significant cytotoxicity. These results suggested that globulusin A ( 1) and eucaglobulin ( 4), which were isolated as antioxidants from E. globulus, also had anti-inflammatory as well as anti-melanogenesis activity.