Atrovirinone inhibits pro-inflammatory mediator release from murine macrophages and human whole blood

• Published in: Immunology and cell biology Vol. 84; no. 3; pp. 250 - 258
• Main Authors: Syahida, A, Israf, Daud A, Permana, D, Lajis, NH, Khozirah, S, Afiza, AW, Khaizurin, TA, Somchit, MN, Sulaiman, MR, Nasaruddin, AA
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.06.2006; Blackwell Science Ltd
• Subjects: Animals; atrovirinone; Benzoquinones - pharmacology; Cell Line; Cells, Cultured; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Dinoprostone - metabolism; Erythrocytes - drug effects; Garcinia atroviridis; Humans; inflammatory mediator; Interferon-gamma - pharmacology; Lipopolysaccharides - pharmacology; Lipoxygenase - chemistry; Lipoxygenase - metabolism; macrophage; Macrophages - drug effects; Mice; NF-kappa B - metabolism; Nitric Oxide - metabolism; Nitrites - metabolism; Oxidative Stress; Signal Transduction; Tumor Necrosis Factor-alpha - metabolism; whole blood
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1111/j.1440-1711.2006.01426.x

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‐α 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‐γ‐induced RAW 264.7 cells and whole blood, with inhibitory concentration (IC)50 values of 4.62 ± 0.65 and 9.33 ± 1.47 μmol/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 μmol/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‐α from RAW 264.7 cells in a dose‐responsive manner, with IC50 values of 5.99 ± 0.62 and 11.56 ± 0.04 μmol/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‐κB pathway and also by the inhibition of the COX/lipoxygenase enzyme activity.