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

Kirubakaran Shanmugam, Lina Holmquist, Megan Steele, Grant Stuchbury, Katrin Berbaum, Oliver Schulz, Obdulio Benavente García, Julián Castillo, Jim Burnell, Vernon Garcia Rivas, Geoff Dobson, Gerald Münch
Mol. Nutr. Food Res.. 2008-04-01; 52(4): 427-438
DOI: 10.1002/mnfr.200700180

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1. Mol Nutr Food Res. 2008 Apr;52(4):427-38. doi: 10.1002/mnfr.200700180.

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

Shanmugam K(1), Holmquist L, Steele M, Stuchbury G, Berbaum K, Schulz O,
Benavente García O, Castillo J, Burnell J, Garcia Rivas V, Dobson G, Münch G.

Author information:
(1)Biochemistry and Molecular Biology, James Cook University, Townsville,
Australia. Fax: + 61-7-4781-6078.

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 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).

DOI: 10.1002/mnfr.200700180
PMID: 18186104 [Indexed for MEDLINE]


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