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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Curcumin induces glutathione biosynthesis and inhibits NF-kappaB activation and interleukin-8 release in alveolar epithelial cells: mechanism of free radical scavenging activity.

Authors: Biswas, Saibal K; McClure, Danny; Jimenez, Luis A; Megson, Ian L; Rahman, Irfan

Published In Antioxid Redox Signal, (2005 Jan-Feb)

Abstract: Oxidants and tumor necrosis factor-alpha (TNF-alpha) activate transcription factors such as nuclear factor-kappaB (NF-kappaB), which is involved in the transcription of proinflammatory mediators, including interleukin-8 (IL-8). Curcumin (diferuloylmethane) is a naturally occurring flavonoid present in the spice turmeric, which has a long traditional use as a chemotherapeutic agent for many diseases. We hypothesize that curcumin may possess both antioxidant and antiinflammatory properties by increasing the glutathione levels and inhibiting oxidant- and cytokine-induced NF-kappaB activation and IL-8 release from cultured alveolar epithelial cells (A549). Treatment of A549 cells with hydrogen peroxide (H2O2; 100 microM) and TNF-alpha (10 ng/ml) significantly increased NF-kappaB and activator protein-1 (AP-1) activation, as well as IL-8 release. Curcumin inhibited both H2O2- and TNF-alpha-mediated activation of NF-kappaB and AP-1, and IL-8 release. Furthermore, an increased level of GSH and glutamylcysteine ligase catalytic subunit mRNA expression was observed in curcumin-treated cells as compared with untreated cells. Curcumin interacted directly with superoxide anion (O2*-) and hydroxyl radical (*OH) as shown by electron paramagnetic resonance, quenching the interaction of the radicals with the spin trap, Tempone-H. This suggests that curcumin has multiple properties: as an oxygen radical scavenger, antioxidant through modulation of glutathione levels, and antiinflammatory agent through inhibition of IL-8 release in lung cells.

PubMed ID: 15650394 Exiting the NIEHS site

MeSH Terms: Anti-Inflammatory Agents/pharmacology; Antineoplastic Agents/pharmacology*; Antioxidants/pharmacology; Cell Line, Tumor; Cell Nucleus/metabolism; Curcumin/pharmacology*; Electron Spin Resonance Spectroscopy; Enzyme Inhibitors/pharmacology*; Enzyme-Linked Immunosorbent Assay; Epithelial Cells/cytology*; Epithelial Cells/drug effects; Free Radical Scavengers/pharmacology*; Free Radicals; Glutamate-Cysteine Ligase/metabolism; Glutathione/metabolism*; Humans; Hydrogen Peroxide/pharmacology; Interleukin-8/metabolism*; Models, Chemical; NF-kappa B/metabolism*; Oxygen/metabolism; Piperidines/pharmacology; Pulmonary Alveoli/cytology*; Pulmonary Alveoli/drug effects; RNA, Messenger/metabolism; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Trans-Activation (Genetics); Transcription Factor AP-1/metabolism; Tumor Necrosis Factor-alpha/metabolism

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