Effects of naturally occurring prenylated flavonoids on enzymes metabolizing arachidonic acid: Cyclooxygenases and lipoxygenases

被引:206
作者
Chi, YS
Jong, HG
Son, KH
Chang, HW
Kang, SS
Kim, HP [1 ]
机构
[1] Kangweon Natl Univ, Coll Pharm, Chunchon 200701, South Korea
[2] Andong Natl Univ, Dept Food & Nutr, Andong, South Korea
[3] Yeungnam Univ, Coll Pharm, Gyongsan, South Korea
[4] Seoul Natl Univ, Inst Nat Prod Res, Seoul 151742, South Korea
关键词
flavonoid; prenylated flavonoid; sophoraflavanone; sanggenon; cyclooxygenases; lipoxygenases; anti-inflammatory activity;
D O I
10.1016/S0006-2952(01)00773-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Prenylated flavonoids are chemical entities having an isoprenyl, a geranyl, a 1, 1-dimethylallyl, and/or a lavandulyl moiety as part of their flavonoid backbone structure. In this study, the effects of 19 naturally occurring prenylated flavonoids, isolated from medicinal plants, on cyclooxygenase (COX)-1 and COX-2 and on 5-lipoxygenase (5-LOX) and 12-LOX were investigated using [C-14]arachidonic acid as a substrate. The homogenates of bovine platelets and polymorphonuclear leukocytes were used as COX-1, 12-LOX, and 5-LOX enzyme sources; the homogenate of aspirin-pretreated lipopolysaccharide-induced RAW 264.7 cells was used for the COX-2 enzyme source. Among the 19 prenylated flavonoids, morusin, kuwanon C, sanggenon B, sanggenon D and kazinol B inhibited COX-2 activity (IC50 = 73-100 muM), but the potencies were far less than that of NS-398 (IC50 = 2.9 muM). In contrast, many prenylated flavonoids, such as kuraridin, kuwanon C and sophoraisoflavanone A, inhibited COX-1 activity. Of the COX-1 inhibiting prenylated flavonoids, kuraridin, kurarinone, and sophoraflavanone G, all having a C-8 lavandulyl moiety, showed potent activity (IC50 = 0.1 to 1 muM) comparable to that of indomethacin (IC50 = 0.7 muM). Most of the prenylated flavonoids tested: inhibited 5-LOX activity with ic,o values ranging from 0.09 to 100 AM. Of these, only kuwanon C, papyriflavonol A and sophoraflavanone G showed inhibitory activity against 12-LOX at low concentration ranges (IC50 = 19-69 muM) comparable to that of NDGA (IC50 = 2.6 muM). Our results suggest that the position and the nature of the prenyl substitution greatly influence in vitro biological activities of these molecules. (C) 2001 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:1185 / 1191
页数:7
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