Plant-derived polyphenols attenuate lipopolysaccharide-induced nitric oxide and tumour necrosis factor production in murine microglia and macrophages

Molecular Nutrition & Food Research
Kirubakaran ShanmugamGerald Münch

Abstract

Lipopolysaccharides released during bacterial infections induce the expression of pro-inflammatory cytokines and lead to complications such as neuronal damage in the CNS and septic shock in the periphery. While the initial infection is treated by antibiotics, anti-inflammatory agents would be advantageous add-on medications. In order to identify such compounds, we have compared 29 commercially available polyphenol-containing plant extracts and pure compounds for their ability to prevent LPS-induced up-regulation of NO production. Among the botanical extracts, bearberry and grape seed were the most active preparations, exhibiting IC(50) values of around 20 mug/mL. Among the pure compounds, IC(50) values for apigenin, diosmetin and silybin were 15, 19 and 12 muM, in N-11 murine microglia, and 7, 16 and 25 muM, in RAW 264.7 murine macrophages, respectively. In addition, these flavonoids were also able to down-regulate LPS-induced tumour necrosis factor production. Structure-activity relationships of the flavonoids demonstrated three distinct principles: (i) flavonoid-aglycons are more potent than the corresponding glycosides, (ii) flavonoids with a 4'-OH substitution in the B-ring are more potent than those with a 3'-OH-4'-methoxy...Continue Reading

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