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Poly (ADP-ribose) polymerase-1-inhibiting flavonoids attenuate cytokine release in blood from male patients with chronic obstructive pulmonary disease or type 2 diabetes.

Weseler, AR, Geraets, L, Moonen, HJ, Manders, RJ, van Loon, LJ, Pennings, HJ, Wouters, EF, Bast, A and Hageman, GJ (2009) Poly (ADP-ribose) polymerase-1-inhibiting flavonoids attenuate cytokine release in blood from male patients with chronic obstructive pulmonary disease or type 2 diabetes. J Nutr, 139 (5). pp. 952-957.

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Abstract

Recently, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo. PARP-1 is recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D). In this study, we assessed the antiinflammatory effects of flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men. A total of 10 COPD, 10 T2D patients, and 10 healthy volunteers matched for age and BMI were recruited. Blood from each participant was exposed to 1 microg/L lipopolysaccharide (LPS) over 16 h with or without preincubation with 10 micromol/L of flavone, fisetin, morin, or tricetin. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, -8, and -10 were measured in the supernatant. Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/- SEM): -41 +/- 4% (fisetin) and -31 +/- 4% (tricetin); P < 0.001] and IL-6 in blood from T2D patients [-31 +/- 5% (fisetin) and -29 +/- 6% (tricetin); P < or = 0.001]. Moreover, LPS-induced changes in TNFalpha and IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin. The PARP-1-inhibiting flavonoids fisetin and tricetin were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as nutraceutical agents for these patient groups.

Item Type: Article
Authors :
NameEmailORCID
Weseler, ARUNSPECIFIEDUNSPECIFIED
Geraets, LUNSPECIFIEDUNSPECIFIED
Moonen, HJUNSPECIFIEDUNSPECIFIED
Manders, RJr.manders@surrey.ac.ukUNSPECIFIED
van Loon, LJUNSPECIFIEDUNSPECIFIED
Pennings, HJUNSPECIFIEDUNSPECIFIED
Wouters, EFUNSPECIFIEDUNSPECIFIED
Bast, AUNSPECIFIEDUNSPECIFIED
Hageman, GJUNSPECIFIEDUNSPECIFIED
Date : May 2009
Identification Number : https://doi.org/10.3945/jn.108.102756
Uncontrolled Keywords : Aged, Chromones, Cytokines, Diabetes Mellitus, Type 2, Enzyme Inhibitors, Flavonoids, Humans, Interleukin-1, Interleukin-10, Interleukin-8, Lipopolysaccharides, Male, Middle Aged, Poly(ADP-ribose) Polymerase Inhibitors, Pulmonary Disease, Chronic Obstructive, Tumor Necrosis Factor-alpha
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:26
Last Modified : 17 May 2017 14:49
URI: http://epubs.surrey.ac.uk/id/eprint/827788

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