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“术”(白术和苍术)对1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷(DOI)诱导的小鼠头部抽搐反应的药理作用(I)。

Pharmacological effects of "jutsu" (Atractylodis rhizome and Atractylodis lanceae rhizome) on 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head twitch response in mice (I).

作者信息

Murayama Chiaki, Wang Ching-Chiung, Michihara Seiwa, Norimoto Hisayoshi

机构信息

Kampo Research Laboratories, Kracie Pharma Ltd., Kanebo machi 3-1, Takaoka, Toyama 933-0856, Japan.

School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.

出版信息

Molecules. 2014 Sep 18;19(9):14979-86. doi: 10.3390/molecules190914979.

Abstract

Hallucinations are a common non-motor symptom of Parkinson's disease and various forms of dementias. Yokukansan and Yokukansankachimpihange have attracted attention due to their effectiveness in the treatment of hallucinations of dementia. To clarify which component in these formulas contribute to the effects, at first, we focused on their differences in compositions to examine the pharmacological effects on the selective 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head-twitch response (HTR) in mice that has been used as animal hallucination model. Results indicated that water extract of Byaku-jutsu (Atractylodes japonica) showed a stronger inhibitory effect on DOI-induced HTR than that of So-jutsu (A. lancea) corresponding to their major constituents of atractylenolide III and β-eudesmol, and suggested that the major constituents should be active constituents contributing to the antihallucination effects of Byaku- and So-jutsu. Besides, the part B-C ring (butenolide) in atractylenolide III was found to be similar to the structure of serotonin and suggested that the B-C ring may partially play role in antagonistic activity against serotonin receptors. Thus, a novel, rational design of butenolide-related compounds may as potential lead compounds for new drug development. Analysis of the chemical components of Byaku- and So-jutsu and further study on their structure-activity relationships are currently in progress.

摘要

幻觉是帕金森病和各种形式痴呆症常见的非运动症状。由于其在治疗痴呆症幻觉方面的有效性, yokukansan和yokukansankachimpihange已引起关注。为了阐明这些方剂中的哪些成分起作用,首先,我们关注它们在成分上的差异,以研究对选择性5-HT2A/2C激动剂1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷(DOI)诱导的小鼠头部抽搐反应(HTR)的药理作用,该反应已被用作动物幻觉模型。结果表明,白术(Atractylodes japonica)的水提取物对DOI诱导的HTR的抑制作用比苍术(A. lancea)更强,这与它们的主要成分苍术内酯III和β-桉叶醇相对应,表明主要成分应该是白术和苍术抗幻觉作用的活性成分。此外,发现苍术内酯III中的B-C环(丁烯内酯)与血清素的结构相似,表明B-C环可能部分参与对血清素受体的拮抗活性。因此,丁烯内酯相关化合物的新颖、合理设计可能作为新药开发的潜在先导化合物。白术和苍术化学成分的分析及其构效关系的进一步研究目前正在进行中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79e2/6271365/5896621963be/molecules-19-14979-g001.jpg

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