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Nutrition and Disease

Poly (ADP-ribose) Polymerase-1–Inhibiting Flavonoids Attenuate Cytokine Release in Blood from Male Patients with Chronic Obstructive Pulmonary Disease or Type 2 Diabetes^1,2

³ Department of Health Risk Analysis and Toxicology ⁴ Department of Pharmacology and Toxicology ⁵ Department of Human Movement Sciences ⁶ Department of Respiratory Medicine, Maastricht University Medical Centre+, Maastricht 6200 MD, The Netherlands ⁷ Centre for Integrated Rehabilitation Organ Failure, Haelen 6080 AB, The Netherlands

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-B 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 µg/L lipopolysaccharide (LPS) over 16 h with or without preincubation with 10 µmol/L of flavone, fisetin, morin, or tricetin. Concentrations of tumor necrosis factor (TNF)-, interleukin (IL)-6, -8, and -10 were measured in the supernatant. Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNF 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 0.001]. Moreover, LPS-induced changes in TNF 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.

^* To whom correspondence should be addressed. E-mail: a.weseler{at}farmaco.unimaas.nl.

Manuscript received 26 November 2008. Initial review completed 1 January 2009. Revision accepted 16 February 2009.