Inhibition of nitric oxide synthase expression by a methanolic extract of Crescentia alata and its derived flavonols
Inhibition of nitric oxide synthase expression by a methanolic extract of Crescentia alata and its derived flavonols
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DOI：
10.1016/s0024-3205(01)01425-4
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发表时间：
2001-12-21
期刊：
影响因子：
6.1
通讯作者：
Aquino, R
中科院分区：
文献类型：
--
作者：
Autore, G;Rastrelli, L;Aquino, R
为了验证在危地马拉传统医学中Crescentia阿拉塔（Bignoniaceae）作为抗肿瘤药物的用途，在体内评价了甲醇（MeOH）提取物对大鼠角叉菜胶足水肿的抗肿瘤活性，并在体外评价了其对大肠杆菌脂多糖（LPS）诱导的一氧化氮（NO）产生和J774.A1巨噬细胞系中诱导型一氧化氮合酶（iNOS）表达的抗肿瘤活性。该提取物在最高测试剂量下在体内发挥显著的抗炎活性。相同的提取物在体外表现出对诱导型一氧化氮合酶表达和对LPS引发的J774.A1细胞中NO形成的抑制活性。提取物的后续分级和分析导致分离和表征为两种黄酮醇糖苷的主要成分：槲皮素3-O-alpha-L-吡喃鼠李糖基-（1->6）-beta-D-吡喃葡萄糖苷（芦丁）1、山奈酚3-O-alpha-L-吡喃鼠李糖基-（1->6）-beta-D-吡喃葡萄糖苷（山奈酚3-O-芸香糖苷）2和黄酮醇苷元山奈酚3。通过波谱方法鉴定了它们的结构。黄酮醇1-3的生物测定导向分析表明，山奈酚（3）是甲醇提取物中含有的最具活性的化合物，因为它在体外降低LPS致敏的J774.A1细胞中的NO产生和iNOS表达，而芦丁（1）和山奈酚3-O-芸香糖苷（2）没有显示出显著的活性。甲醇提取物和所有测试的黄酮类化合物在体外对J774.A1巨噬细胞系没有显示出显著的细胞毒性作用。(C)2001 Elsevier Science Inc. All rights reserved.
In order to validate the use of Crescentia alata (Bignoniaceae) in the traditional medicine of Guatemala as an antiinflammatory remedy, the methanolic (MeOH) extract has been evaluated in vivo for antiinflammatory activity on carrageenin paw edema in rats and in vitro on Escherichia coli lipopolysaccharide-(LPS)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in J774.A1 macrophage cell line. This extract exerted in vivo a significant anti-inflammatory activity at the highest dose tested. The same extract showed in vitro an inhibitory activity on inducible nitric oxide synthase expression and on NO formation in LPS-primed J774.A1 cells. Subsequent fractionation and analysis of the extract has led to the isolation and characterization as major constituents of two flavonol glycosides: quercetin 3-O-alpha-L-rhamnopyranosyl-(1->6)-beta-D-glucopyranoside (rutin) 1, kaempferol 3-O-alpha-L-rhamnopyranosyl-(1->6)-beta-D-glucopyranoside (kaempferol 3-O-rutinoside) 2, and flavonol aglycone, kaempferol 3. Their structures were elucidated by spectral methods. The bioassay-directed analysis of flavonols 1-3 indicated that kaempferol (3) was the most active compound contained in the MeOH extract because it reduced in vitro both NO production and iNOS expression in LPS-primed J774.A1 cells, whereas rutin (1) and kaempferol 3-O-rutinoside (2) showed no significant activity. The MeOH extract and all of flavonoids tested did not show in vitro significant cytotoxic effect in J774.A1 macrophage cell line. (C) 2001 Elsevier Science Inc. All rights reserved.