Differential effects of resveratrol and its natural analogs, piceatannol and 3,5,4′-trans-trimethoxystilbene, on anti-inflammatory heme oxigenase-1 expression in RAW264.7 macrophages

Authors

  • Yong Son,

    1. Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine, Iksan, Republic of Korea
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  • Hun-Taeg Chung,

    1. Department of Biological Science, University of Ulsan, Ulsan, Republic of Korea
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  • Hyun-Ock Pae

    Corresponding author
    1. Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Republic of Korea
    • Address for correspondence: Hyun-Ock Pae, Ph. D, Professor, Department of Microbiology and Immunology, Wonkwang University School of Medicine, 460 Iksandae-ro, Iksan 570–749, Republic of Korea. Tel.: +82-63-850–6925; Fax: +82-63-842–6925; E-mail: hopae@wku.ac.kr.

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Abstract

Resveratrol (Res) and its two natural analogs that are also related to Res metabolism, piceatannol (Pic) and 3,5,4′-trans-trimethoxystilbene (TMS), were compared in their ability to suppress lipopolysaccharide (LPS)-induced production of proinflammatory tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and to induce anti-inflammatory heme oxygenase-1 (HO-1) expression in RAW264.7 macrophages. At non-cytotoxic concentrations, they differentially suppressed LPS-induced production of TNF-α and IL-1β; the relative potency for suppression of TNF-α and IL-1β production was Pic > Res > TMS. Res and Pic differentially induced HO-1 expression; Pic, which possesses four hydroxyl groups, was more active in inducing HO-1 expression than Res that contains three hydroxyl groups. TMS, which has none of hydroxyl groups, failed to induce HO-1 expression. These findings suggest that the hydroxyl groups of Res analogs are important for suppression of TNF-α and IL-1β production and HO-1 expression. Interestingly, protoporphyrin-IX, a competitive inhibitor of HO-1 activity, partly attenuated the inhibitory effects of Res and Pic (but not TMS) on TNF-α and IL-1β production, suggesting that suppression of TNF-α and IL-1β production correlates at least in part with HO-1 expression. Overall, the ability of Res analogs to induce HO-1 expression may provide one of possible mechanisms of their anti-inflammatory action. © 2013 BioFactors, 40(1):138–145, 2014.

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