Poly (ADP-ribose) Polymerase-1-Inhibiting Flavonoids Attenuate Cytokine Release in Blood from Male Patients with Chronic Obstructive Pulmonary Disease or Type 2 Diabetes
2009
Weseler, Antje R. | Geraets, Liesbeth | Moonen, Harald J.J. | Manders, Ralph J.F. | van Loon, Luc J.C. | Pennings, Herman-Jan | Wouters, Emiel F.M. | Bast, Aalt | Hageman, Geja J.
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-κB 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)-α, interleukin (IL)-6, -8, and -10 were measured in the supernatant. Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFα 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 [less-than or equal to] 0.001]. Moreover, LPS-induced changes in TNFα 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.
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