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

Oleh:

Weseler, Antje R. ; Geraets, Liesbeth ; Moonen, Harald J. J.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 139 no. 05 (May 2009), page 952-957.
Topik: Nutrition and Disease

Ketersediaan

Perpustakaan FK Nomor Panggil: J42.K.2009.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

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-{kappa}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)-{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 TNF{alpha} 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{alpha} 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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