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

Lipopolysaccharides released during bacterial infections induce the expression of proinflammatory 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 μg/mL. Among the pure compounds, IC 50 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) flavonoidaglycons are more potent than the corresponding glycosides, (ii) flavonoids with a 4"²-OH substitution in the B-ring are more potent than those with a 3"²-OH-4"²-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).