Effects of plant‐derived polyphenols on TNF‐α and nitric oxide production induced by advanced glycation endproducts

Abstract

Advanced glycation endproducts (AGEs) accumulate on protein deposits including the beta-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-alpha) 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-alpha 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 approximately 10 microM. In contrast, TNF-alpha 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 >or=10 microg/mL and >or=50 microg/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.

Determination of anti-inflammatory activities of standardised preparations of plant- and mushroom-based foods

“…The activation of macrophages and microglia leads to secretion of inflammatory molecules such as the proinflammatory cytokine TNF-α and the free radical NO, which play an important role in inflammation and nitroxidative stress in many age-related diseases, including Alzheimer's disease (AD) [14]. In the assay systems used here, the bacterial surface molecule lipopolysaccharide and the cytokine IFN-γ were used to activate microglia, and NO and TNF-α release were used as readouts [15].…”

Molecular mechanisms for anti‐aging by natural dietary compounds

“…Pretreatment of neuron cells and retinal pigment epithelium cells with baicalein prevents the H 2 O 2 -induced oxidative damage, mitochondrial dysfunction and cell death that may prevent age-associated eye pathology and neurodegeneration [123,124]. Diosmetin is a methoxy flavone commonly presented in citrus fruits, reduces AGEs-induced inflammatory cytokines production thus may reduce neuroinflammation [125].…”

Polyphenols in Regulation of Redox Signaling and Inflammation During Cardiovascular Diseases

“…Phenolic compounds are known to modify NO content in tissues. A recent study by Chandler et al [53], 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 (advanced glycation endproducts)-induced NO and TNF-alpha production. All five tested samples inhibited BSA-AGE-induced NO production in a dose-dependent manner with apigenin and diosmetin being most potent and exhibited EC [50] values approximately 10 lM.…”