ABSTRACT
Many plant-derived natural compounds have been reported previously to inhibit the production of important pro-inflammatory mediators such as nitric oxide, prostaglandin E2, TNF-alpha and reactive oxygen species by suppressing inducible enzyme expression via inhibition of the mitogen-activated protein kinase pathway and nuclear translocation of critical transcription factors. This study evaluates the effects of atrovirinone [2-(1-methoxycarbonyl-4,6-dihydroxyphenoxy)-3-methoxy-5,6-di-(3-methyl-2-butenyl)-1,4-benzoquinone)], a benzoquinone that we have previously isolated from Garcinia atroviridis, on two cellular systems that are repeatedly used in the analysis of anti-inflammatory bioactive compounds, namely, RAW 264.7 macrophage cells and whole blood. Atrovirinone inhibited the production of both nitric oxide and prostaglandin E2 from LPS-induced and IFN-gamma-induced RAW 264.7 cells and whole blood, with inhibitory concentration (IC)50 values of 4.62 +/- 0.65 and 9.33 +/- 1.47 micromol/L, respectively. Analysis of thromboxane B2 (TXB2) secretion from whole blood stimulated by either the cyclooxygenase (COX)-1 or the COX-2 pathway showed that atrovirinone inhibits the generation of TXB2 by both pathways, with IC50 values of 7.41 +/- 0.92 and 2.10 +/- 0.48 micromol/L, respectively. Analysis of IC50 ratios showed that atrovirinone was more COX-2 selective in its inhibition of TXB2, with a ratio of 0.32. Atrovirinone also inhibited the generation of intracellular reactive oxygen species and the secretion of TNF-alpha from RAW 264.7 cells in a dose-responsive manner, with IC50 values of 5.99 +/- 0.62 and 11.56 +/- 0.04 micromol/L, respectively. Lipoxygenase activity was also moderately inhibited by atrovirinone. Our results suggest that atrovirinone acts on important pro-inflammatory mediators possibly by the inhibition of the nuclear factor-kappaB pathway and also by the inhibition of the COX/lipoxygenase enzyme activity.
Subject(s)
Benzoquinones/pharmacology , Dinoprostone/metabolism , Erythrocytes/drug effects , Macrophages/drug effects , Nitric Oxide/metabolism , Animals , Cell Line , Cells, Cultured , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , Humans , Interferon-gamma/pharmacology , Lipopolysaccharides/pharmacology , Lipoxygenase/chemistry , Lipoxygenase/metabolism , Mice , NF-kappa B/metabolism , Nitrites/metabolism , Oxidative Stress , Signal Transduction , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Two new prenylated compounds, the benzoquinone atrovirinone (1) and the depsidone atrovirisidone (2), were isolated from the roots of Garcinia atroviridis. Their structures were determined on the basis of the analysis of spectroscopic data. While compound 2 showed some cytotoxicity against HeLa cells, both compounds 1 and 2 were only mildly inhibitory toward Bacillus cereus and Staphylococcus aureus.
Subject(s)
Anti-Infective Agents/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Benzoquinones/isolation & purification , Lactones/isolation & purification , Plants, Medicinal/chemistry , Adolescent , Anti-Bacterial Agents , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Aspergillus ochraceus/drug effects , Bacillus cereus/drug effects , Benzoquinones/chemistry , Benzoquinones/pharmacology , Candida albicans/drug effects , Colchicine/pharmacology , Doxorubicin/pharmacology , Escherichia coli/drug effects , Gas Chromatography-Mass Spectrometry , HeLa Cells , Humans , Lactones/chemistry , Lactones/pharmacology , Magnetic Resonance Spectroscopy , Malaysia , Molecular Structure , Plant Roots/chemistry , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Staphylococcus aureus/drug effects , Streptomycin/pharmacology , Tumor Cells, Cultured/drug effectsABSTRACT
A new anthraquinone, 2-hydroxymethyl-10-hydroxy-1,4-anthraquinone (1), was isolated from Hedyotis herbacea along with three other known derivatives: 1,4-dihydroxy-2-hydroxymethylanthraquinone (2); 2, 3-dimethoxy-9-hydroxy-1,4-anthraquinone; and 1,4-dihydroxy-2, 3-dimethoxyanthraquinone. The structure of 1 was determined based on analysis of its spectroscopic data.
