NPI-031G (puerarin) reduces anxiogenic effects of alcohol withdrawal or benzodiazepine inverse or 5-HT2C agonists
NPI-031G (puerarin) reduces anxiogenic effects of alcohol withdrawal or benzodiazepine inverse or 5-HT2C agonists
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DOI：
10.1016/s0091-3057(03)00114-x
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发表时间：
2003-06-01
影响因子：
3.6
通讯作者：
Lee, DY
中科院分区：
文献类型：
--
作者：
Overstreet, DH;Kralic, JE;Lee, DY
由于葛根提取物在中国已被用作解酒药物已有多个世纪，因此我们测试了 NPI-031G（葛根素）（一种从葛根中分离出的异黄酮）抵抗与长期饮酒戒断相关的焦虑作用的能力。 NPI-031G（50 和 150 mg/kg ip）显着增加了因戒酒 17 天（7%）饮食而减少的社交互动和运动活动。 NPI-031G 的作用类似于苯二氮卓类拮抗剂氟马西尼 (5 mg/kg) 和 5-HT2C 拮抗剂 SB 242084 (1 mg/kg)。在另一项研究中，对照大鼠接受 NPI-031G 预处理（30 分钟），然后给予致焦虑化合物 DMCM（一种苯二氮卓反向激动剂）或 Ro 60 0175（一种 5-HT2C 激动剂）。 NPI-031G 显着抵消了这两种化合物引起的社交互动的减少。为了确定 NPI-031G 的潜在作用机制，从未经治疗的大鼠的大脑皮层中分离出突触神经体，并进行了氯离子吸收测定。 NPI-031G 对刺激 GABA(A) 激动剂蝇蕈醇吸收氯离子没有任何影响。然而，它降低了浓度为 100 μM 的苯二氮卓类激动剂氟硝西泮对蝇蕈醇刺激的氯离子吸收的增强作用。在此浓度下还观察到[H-3]氟硝西泮结合减少。这些发现与 NPI-031G 是弱苯二氮卓位点拮抗剂一致。 (C) 2003 Elsevier Science Inc. 保留所有权利。
Because extracts of kudzu have been used as a hangover remedy in China for many centuries, we tested the ability of NPI-031G (puerarin), an isoflavone isolated from kudzu, to counteract anxiogenic effects associated with withdrawal from chronic alcohol exposure. NPI-031G (50 and 150 mg/kg ip) significantly increased the social interaction and locomotor activity reduced by withdrawal from 17 days of alcohol (7%) diet. The effects of NPI-031G resembled those of the benzodiazepine antagonist, flumazenil (5 mg/kg), and the 5-HT2C antagonist, SB 242084 (1 mg/kg). In a separate study, control rats were pretreated with NPI-031G (30 min) and then given the anxiogenic compounds DMCM, a benzodiazepine inverse agonist, or Ro 60 0175, a 5-HT2C agonist. NPI-031G significantly counteracted the reduction in social interaction induced by either compound. To identify a potential mechanism of action of NPI-031G, synaptoneurosomes were isolated from the cerebral cortex of untreated rats and chloride uptake assays were carried out. NPI-031G did not have any effect on the stimulation of chloride uptake by muscimol, a GABA(A) agonist. However, it reduced the potentiation of muscimol-stimulated chloride uptake by flunitrazepam, a benzodiazepine agonist, at a concentration of 100 muM. A reduction in [H-3]flunitrazepam binding was also seen at this concentration. These findings are consistent with NPI-031G being a weak benzodiazepine site antagonist. (C) 2003 Elsevier Science Inc. All rights reserved.