| Abstract |
Studies on the chemical constituents of a gorgonian coral identified as Pinnigorgia sp. have resulted in the isolation of 5 new 4,5;5,6;9,11-triseco-4(5→6),5(6→7)-diabeo-ergostane, pinnigorgiols A−E (1−5); 11 new 9,11-secosteroids, pinnisterols A−K (6−16); five new sterols, (22R)-24-methyl-5-ene-3β-ol-22-acetate (17), (22E,24R)- ergosta-5,22-diene-3β,11α-diol (18), (24S)-ergosta-5-ene-3β,11α-diol (19), 5α,6α- epoxy-23-demethylgorgost-8(14)-ene-3β,7α-diol (20), 5α,6α-epoxy-23-demethyl- gorgost-8-ene-3β,7α-diol (21); and six known compounds, cerevisterol (22), 23-demethylgorgost-7-ene-3,5,6-triol (23), ergosterol peroxide (24), (22R,23R,24R)-5,8-epidioxy-22,23-methylene-24-methylcholest-6-en-3-ol (25), apo-9′-fucoxanthinone (26), and pubinernoid A (27). The structures of each metabolite were determined by spectroscopic methods, particular by the 1D and 2D NMR experiments. The configurations of metabolite 1−5 were further confirmed by comparative analysis of circular dichroism spectroscopic data.
Each metabolite was screened for anti-hepatofibric and anti-inflammatory activities. Metabolites 1, 2, 4−6, 9, 10, 12, 13, and 23 were found to exhibit cytotoxicity in HSC-T6. Activation of hepatic stellate cells (HSCs) plays a major role in liver fibrosis. During liver fibrosis, extracellular matrix proteins and pro-inflammatory growth factors are overexpressed by activated HSCs. Clearance of activated HSCs by inducing apoptosis is an efficient way to treat liver fibrosis. In the anti-inflammation assay, compounds 1−6, 8, 9, 12, and 15 inhibited the production of superoxide anion and decreased the release of elastase in the human neutrophils that stimulated by formyl-L-methionyl-L-leucyl- L-phenylalanine/cytochalasin B (fMLP/CB). The metabolite 13 only caused the inhibit superoxide anion generation, while the compounds 11 and 26 only resulted in inhibition of elastase release in human neutrophils. Although numerous studies have attempted to characterize marine bioactive compounds with the aim of curing human diseases, the focus on liver diseases is very limited. Further biomedical investigation of the 9,11-secosteroids may warrant the application to be promising bioactive agents for liver disease. |
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