TY - JOUR
T1 - Effects of plant-derived polyphenols on TNF-α and nitric oxide production induced by advanced glycation endproducts
AU - Chandler, Dave
AU - Woldu, Ameha
AU - Rahmadi, Anton
AU - Shanmugam, Kirubakaran
AU - Steiner, Nicole
AU - Wright, Elise
AU - Benavente-García, Obdulio
AU - Schulz, Oliver
AU - Castillo, Julián
AU - Münch, Gerald
PY - 2010
Y1 - 2010
N2 - Advanced glycation endproducts (AGEs) accumulate on protein deposits including the β-amyloid plaques in Alzheimer's disease. AGEs interact with the "receptor for advanced glycation endproducts", and transmit their signals using intracellular reactive oxygen species as second messengers. Ultimately, AGEs induce the expression of a variety of pro-inflammatory markers including the tumor necrosis factor (TNF-α) and inducible nitric oxide (NO) synthase. Antioxidants that act intracellularly, including polyphenols, have been shown to scavenge these "signaling" reactive oxygen species, and thus perform in an anti-inflammatory capacity. This study tested the pure compounds apigenin and diosmetin as well as extracts from silymarin, uva ursi (bearberry) and green olive leaf for their ability to attenuate AGE-induced NO and TNF-α production. All five tested samples inhibited BSA-AGE-induced NO production in a dose-dependent manner. Apigenin and diosmetin were most potent, and exhibited EC50 values ~10μM. In contrast, TNF-α expression was only reduced by apigenin, diosmetin and silymarin; not by the bearberry and green olive leaf extracts. In addition, the silymarin and bearberry extracts caused significant cell death at concentrations ≥10μg/mL and ≥50μg/mL, respectively. In conclusion, we suggest that plant-derived polyphenols might offer therapeutic opportunities to delay the progression of AGE-mediated and receptor for advanced glycation endproducts-mediated neuro-inflammatory diseases including Alzheimer's disease.
AB - Advanced glycation endproducts (AGEs) accumulate on protein deposits including the β-amyloid plaques in Alzheimer's disease. AGEs interact with the "receptor for advanced glycation endproducts", and transmit their signals using intracellular reactive oxygen species as second messengers. Ultimately, AGEs induce the expression of a variety of pro-inflammatory markers including the tumor necrosis factor (TNF-α) and inducible nitric oxide (NO) synthase. Antioxidants that act intracellularly, including polyphenols, have been shown to scavenge these "signaling" reactive oxygen species, and thus perform in an anti-inflammatory capacity. This study tested the pure compounds apigenin and diosmetin as well as extracts from silymarin, uva ursi (bearberry) and green olive leaf for their ability to attenuate AGE-induced NO and TNF-α production. All five tested samples inhibited BSA-AGE-induced NO production in a dose-dependent manner. Apigenin and diosmetin were most potent, and exhibited EC50 values ~10μM. In contrast, TNF-α expression was only reduced by apigenin, diosmetin and silymarin; not by the bearberry and green olive leaf extracts. In addition, the silymarin and bearberry extracts caused significant cell death at concentrations ≥10μg/mL and ≥50μg/mL, respectively. In conclusion, we suggest that plant-derived polyphenols might offer therapeutic opportunities to delay the progression of AGE-mediated and receptor for advanced glycation endproducts-mediated neuro-inflammatory diseases including Alzheimer's disease.
UR - http://handle.uws.edu.au:8081/1959.7/553906
U2 - 10.1002/mnfr.200900504
DO - 10.1002/mnfr.200900504
M3 - Article
SN - 1613-4125
VL - 54
SP - S141-S150
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - Suppl. 2
ER -