Partial agonistic effect of yokukansan on human recombinant serotonin 1A receptors expressed in the membranes of Chinese hamster ovary cells
Partial agonistic effect of yokukansan on human recombinant serotonin 1A receptors expressed in the membranes of Chinese hamster ovary cells
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DOI：
10.1016/j.jep.2009.11.003
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发表时间：
2010-02-03
影响因子：
5.4
通讯作者：
Kase, Yoshio
中科院分区：
文献类型：
--
作者：
Terawaki, Kiyoshi;Ikarashi, Yasushi;Kase, Yoshio
民族药理学相关性：Yokukansan （YKS）是一种传统的日本药物，由七种草药组成，在日本被用于治疗神经症、失眠和痴呆（BPSD）的行为和心理症状。研究目的：本研究的目的是阐明YKS对5-羟色胺（5-HT）1A和5-HT2A受体的内在活性，并确定YKS作用的成分草药。材料和方法：以YKS的干粉提取物、7种成分草药和YKS的类似物为评价对象，这些类似物是在生产过程中从YKS中去除其中一种成分草药而得到的。利用稳定表达人重组5-HT1A或5-HT2A受体的中国仓鼠卵巢细胞膜，进行了5-HT受体的竞争结合试验和[S-35]GTP γ S结合试验，以评估其激动/拮抗活性。结果：YKS （6.25 ~ 400 μ g/ml）呈浓度依赖性地抑制[H-3]8-OH-DPAT与5-HT1A受体的结合。IC50值估计为61.2 μ g/ml。相比之下，YKS未能抑制[H-3]酮色蛋白与5-HT2A受体的结合。7种成分提取物中，只有钩藤（3.13 ~ 50 μ g/ml）对[H-3]8-OH-DPAT与5-HT1A受体的结合具有浓度依赖性，IC50值估计为7.42 μ g/ml。YKS或钩藤提取物使[S-35]GTP γ S与5-HT1A受体的结合增加到完全激动剂5-HT的约50%。从YKS中去除钩藤后，YKS与5-HT1A受体的竞争结合和[S-35]GTP γ S结合都明显减弱，但当从YKS中去除其他成分草药时，这种结合几乎没有变化。结论：YKS对5-HT1A受体具有部分激动作用，其作用机制主要与钩藤钩有关。2009爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Yokukansan (YKS) is a traditional Japanese medicine consisted of seven medicinal herbs and has been used for treatment of neurosis, insomnia, and behavioral and psychological symptoms of dementia (BPSD) in Japan.Aim of the study: The aim of the present study is to clarify the intrinsic activity of YKS on serotonin (5-HT)1A and 5-HT2A receptors and also to determine the constituent herbs which are responsible for the effect of YKS.Materials and methods: The dry powdered extracts of YKS, seven constituent herbs, and YKS-analogues which were produced by eliminating one of the constituent herbs from YKS in the manufacturing process, were used for the evaluation. Competitive binding assays for 5-HT receptors and [S-35]GTP gamma S binding assays for the evaluation of agonistic/antagonistic activity were performed using Chinese hamster ovary cell membranes stably expressing human recombinant 5-HT1A or 5-HT2A receptors.Results: YKS (6.25-400 mu g/ml) concentration-dependently inhibited the binding of [H-3]8-OH-DPAT to 5-HT1A receptors. The IC50 value was estimated to be 61.2 mu g/ml. In contrast, YKS failed to inhibit the binding of [H-3]ketanserin to 5-HT2A receptors. Only Uncaria hook (3.13-50 mu g/ml), of the seven constituent herbal extracts, inhibited the [H-3]8-OH-DPAT binding to 5-HT1A receptors in a concentration-dependent manner, and the IC50 value was estimated to be 7.42 mu g/ml. The extracts of YKS or Uncaria hook increased [S-35]GTP gamma S binding to 5-HT1A receptors to approximately 50% of that of a full agonist, 5-HT. Both the competitive binding and [S-35]GTP gamma S binding of YKS to 5-HT1A receptors were remarkably attenuated by eliminating Uncaria hook from YKS, but it was almost unchanged when one of the other constituent herbs was eliminated from YKS.Conclusion: These results suggest that YKS has a partial agonistic effect on 5-HT1A receptors, which is mainly attributed to Uncaria hook. (C) 2009 Elsevier Ireland Ltd. All rights reserved.