The effects of genistein and puerarin on the activation of nuclear factor-kappaB and the production of tumor necrosis factor-alpha in asthma patients.
Oxidative stress might play an essential role in the pathogenesis of chronic airway inflammatory diseases, indicating that antioxidant therapy may have a potential effect in controlling chronic airway inflammatory diseases. The aim of the present study was to investigate the effect of antioxidants genistein and puerarin on the activation of nuclear factor-kappaB (NF-kappaB) and the production of tumor necrosis factor-alpha (TNF-alpha) in peripheral blood mononuclear cells (PBMCs) in asthma patients. PBMCs were isolated from blood samples of 32 asthma patients and 31 healthy persons, and randomly divided into four groups, control group, dexamethasone group, genistein group and puerarin group. The expression of NF-kappaB in nuclei was analysed by immunocytochemical staining. The level of TNF-alpha was measured by radioimmunoassay. Results showed that the percentage of NF-kappaB positive cells in PBMCs and the level of TNF-alpha in PBMCs supernatants were significantly higher in asthma patients 23.1 +/- 6.7%, 2.10 +/- 0.38 microg/L than in those of healthy persons 7.2 +/- 2.9%, 0.86 +/- 0.53 microg/L (p all < 0.01). There was a positive correlation between the percentage of NF-kappaB positive cells and the level of TNF-alpha in asthma patients (r = 0.709, p < 0.01). The percentages of NF-kappaB positive cells in PBMCs were significantly decreased in the genistein group 15.2 +/- 5.4% and in the puerarin group 16.2 +/- 5.1% than those in control groups 23.1 +/- 6.7% in asthma patients (p respectively < 0.01, < 0.05). The levels of TNF-alpha in PBMCs supernatants were remarkably decreased in genistein group 1.08 +/- 0.40 microg/L and in puerarin group 1.24 +/- 0.29 microg/L than those in control group 2.10 +/- 0.38 microg/L in asthma patients (p all < 0.01). There were positive correlations between the percentages of NF-kappaB positive cells and the levels of TNF-alpha in genistein group (r = 0.579, p < 0.01) and in puerarin group (r = 0.665, p < 0.01) in asthma patients. These results show that the activation of NF-kappaB and TNF-alpha pathway of PBMCs may play an important role in the pathogenesis of asthma. Genistein, and puerarin could inhibit the pathway of NF-kappaB and TNF-alpha in asthma patients, so it was implicated that asthma patients will benefit from the antioxidants genistein and puerarin.
Department of Gerontal Respiratory Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, PR China. liu_xiaoju@yahoo.com.cn
Xiao-Ju
XJ
Liu
Jin
J
Zhao
Xing-Yu
XY
Gu
D000328:Adult; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001249:Asthma / Q000378:metabolism*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014665:Vasodilator Agents / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D007529:Isoflavones; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D019833:Genistein; C033607:puerarin