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Effects of plant‐derived polyphenols on TNF‐α and nitric oxide production induced by advanced glycation endproducts
Author(s) -
Chandler Dave,
Woldu Ameha,
Rahmadi Anton,
Shanmugam Kirubakaran,
Steiner Nicole,
Wright Elise,
BenaventeGarcía Obdulio,
Schulz Oliver,
Castillo Julián,
Münch Gerald
Publication year - 2010
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200900504
Subject(s) - nitric oxide , polyphenol , chemistry , glycation , tumor necrosis factor alpha , biochemistry , pharmacology , medicine , immunology , antioxidant , organic chemistry , receptor
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 EC 50 values ∼10 μM. 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 ≥10 μg/mL and ≥50 μg/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.