The effects of twelve representative flavonoids on tissue factor expression in human monocytes: Structure-activity relationships

In this study, we examined the effects of 12 representative natural flavonoids from four different types on TF procoagulant activity in human monocytes stimulated by lipopolysaccharide (LPS). The results showed that eight flavonoids produced dose- dependently inhibitory activities, and in relative order of potency were as follows: luteolin-7, 3′, 4′-trimethyl ether > 3′-hydroxygenkwanin > kaempferol > (-)-epicatechin > persicogenin > quencetin > 5-hydroxy-7, 4′- dimethoxyflavone > genkwanin. However, luteolin, (+)-catechin, puerarin and baicalin showed no obvious effects on TF activity. Preliminary SAR analysis showed that a methoxyl group in the A ring and B ring played a key role in the inhibitory activity, and that a hydroxyl group at C-3 was also a functional group. Furthermore, it was found that an unsaturated bond of C-2 and C-3 in conjugation with a C = O functionality at the C-4 position were not essential. It was also important to note that the presence of a glycosylation group greatly reduced the inhibitory effects. We also found that 3′-hydroxygenkwanin suppressed TF mRNA accumulation. To our knowledge, this is the first time anyone has studied the SARs of several types of flavonoids as they relate to the inhibition of TF activity. These results will surely be helpful in exploring the therapeutic TF inhibitors from flavonoids and further understanding the mechanisms of flavonoids in protection from cardiovascular diseases. © 2009 Elsevier Ltd. All rights reserved.