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

• Published in: Molecular nutrition & food research 2008-04, Vol.52 (4), p.427-438
• Main Authors: Shanmugam, Kirubakaran, Holmquist, Lina, Steele, Megan, Stuchbury, Grant, Berbaum, Katrin, Schulz, Oliver, Benavente García, Obdulio, Castillo, Julián, Burnell, Jim, Garcia Rivas, Vernon, Dobson, Geoff, Münch, Gerald
• Format: Article
• Language: English
• Subjects: Animals; Bacterial meningitis; Biological and medical sciences; Cell Survival - drug effects; Flavonoids; Flavonoids - pharmacology; Food industries; Fundamental and applied biological sciences. Psychology; Inflammation; Lipopolysaccharide; Lipopolysaccharides - toxicity; Macrophage Activation - drug effects; Macrophage Activation - physiology; Macrophages - cytology; Macrophages - drug effects; Macrophages - physiology; Mice; Microglia - cytology; Microglia - drug effects; Microglia - physiology; Nitric Oxide - metabolism; Phenols - pharmacology; Plant Extracts - pharmacology; Polyphenols; Septic shock; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - drug effects; Vitaceae
• ISSN: 1613-4125; 1613-4133; 1521-3803
• DOI: 10.1002/mnfr.200700180

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 IC₅₀ values of around 20 μg/mL. Among the pure compounds, IC₅₀ values for apigenin, diosmetin and silybin were 15, 19 and 12 μM, in N-11 murine microglia, and 7, 16 and 25 μM, 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 substitution, (iii) flavonoids of the flavone type (with a C2=C3 double bond) are more potent than those of the flavanone type (with a at C2-C3 single bond).