Inhibitory Effect of Four Triterpenoids from <i>Trichilia connaroides</i> on Nitric Oxide Production in Lipopolysaccharide-Stimulated RAW264.7 Cells

Abstract

Two new highly rearranged trichiliton-type limonoids (trichilitons G-H, 1-2), and two new cycloartane-type triterpenoids, 21-(E)-coumaroyloxy-5α-cycloart-24-ene-3,23-dione (3) and 21-(E)-feruloyloxy-5α-cycloart-24-ene-3,23-dione (4), were isolated from the stem and bark of Trichilia connaroides. These isolates were elucidated on the basis of detailed spectroscopic analysis, and inhibitory effect of these compounds on lipopolysaccharide-induced nitric oxide production in mouse macrophage RAW264.7 cells was evaluated.Key words Trichilia connaroides; Meliaceae; triterpenoid; nitric oxide production inhibition Trichilia connaroides (WIGHT et ARNOTT) BENTV (Meliaceae), has been used as folk medicine in China for treatment of arthritis, pharyngitis, tonsillitis, and other ailments. 1)Previous chemical investigations on the constituents of T. connaroides led to the discovery of many structurally diverse triterpenoids with complex ring systems, 2-7) which inspired a continuing interest of this plant. Searching for structurally unique and biologically interesting secondary metabolites, we investigated the dichloromethane extract of the stem and bark of this plant. As a result, two new highly rearranged trichiliton-type limonoids (trichilitons G-H, 1-2), and two new cycloartane-type triterpenoids, 21-(E)-coumaroyloxy-5α-cycloart-24-ene-3,23-dione (3) and 21-(E)-feruloyloxy-5α-cycloart-24-ene-3,23-dione (4) were isolated and identificated. Herein we described the isolation, structure elucidation of these compounds, and their inhibitory effects on lipopolysaccharide-induced nitric oxide production in mouse macrophage RAW264.7 cells. Results and DiscussionThe dichloromethane extract of the stem and bark of T. connaroides was chromatographed on MCI, silica gel, and octadecyl silica (ODS) and followed by semi-preparative HPLC to afford four new triterpenoids (1-4) (Fig. 1). The chemical structures of these compounds were determined on the basis of detailed spectroscopic analysis, including high resolutionelectrospray ionization-mass spectrum (HR-ESI-MS), one dimensional (1D)-and 2D-NMR experiments.