Plant-derived polyphenols attenuate lipopolysaccharide-induced nitric oxide and tumour necrosis factor production in murine microglia and macrophages
Shanmugam, Kirubakaran, Holmquist, Lina, Steele, Megan, Stuchbury, Grant, Berbaum, Katrin, Schulz, Oliver, Garcia, Obdulio Benavente, Castillo, Julian, Burnell, Jim, Garcia Rivas, Vernon, Dobson, Geoff, and Muench, Gerald (2008) Plant-derived polyphenols attenuate lipopolysaccharide-induced nitric oxide and tumour necrosis factor production in murine microglia and macrophages. Molecular Nutrition & Food Research, 52 (4). pp. 427-438.
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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 g/mL. Among the pure compounds, IC50 values for apigenin, diosmetin and silybin were 15, 19 and 12 M, in N-11 murine microglia, and 7, 16 and 25 M, 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).
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||bacterial meningitis; flavonoids; inflammation; Lipopolysaccharide; septic shock|
|Date Deposited:||15 Feb 2010 03:55|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110999 Neurosciences not elsewhere classified @ 100%|
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920112 Neurodegenerative Disorders Related to Ageing @ 100%|
|Citation Count from Web of Science||