Indole alkaloids of a Thai medicinal herb, Mitragyna speciosa, that has opioid agonistic effect in guinea-pig ileum
Indole alkaloids of a Thai medicinal herb, Mitragyna speciosa, that has opioid agonistic effect in guinea-pig ileum
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DOI：
10.1055/s-2005-837822
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发表时间：
2005-03-01
期刊：
影响因子：
2.7
通讯作者：
Murayama, T
中科院分区：
文献类型：
--
作者：
Horie, S;Koyama, F;Murayama, T
最近，我们发现大花叶菊中的主要成分米曲吉宁具有阿片激动剂活性，但其微弱的药效并不能解释该植物的鸦片样作用。在本研究中，采用生物测定指导的方法对大叶连翘叶的粗提物进行分级，以寻找除美托宁之外的有效的阿片类激动剂。用电刺激引起的豚鼠回肠痉挛收缩来评价阿片激动剂的活性。大草粗提物以浓度依赖的方式抑制小鼠的抽动收缩。这种抑制作用可被纳洛酮逆转。只有粗碱部分有阿片类物质的作用，其次是分离出5种吲哚生物碱。在这些生物碱中，7-羟基米曲吉宁对电刺激的收缩有最强的阿片作用(PD(2)=8.38+/-0.12)。根据Pd(2)值计算出的药效分别是三氯甲烷和吗啡的30倍和17倍。纳洛酮对7-羟基米曲宁的量效曲线的拮抗作用证实了其阿片类作用。这些结果表明，大刺五加的阿片类作用主要是通过7-羟基美的宁的活性实现的。
Recently, we found that mitragynine, a major constituent of Mitragyna speciosa, has an opioid agonistic activity, but its weak potency could not explain the opium-like effect of this plant. In the present study, bioassay-guided fractionation of the crude extract of the leaves of M. speciosa was carried out to search for potent opioid agonists other than mitragynine. Opioid agonistic activities were evaluated using twitch contraction induced by electrical stimulation in guinea-pig ileum. The crude extract of M. speciosa inhibited the twitch contraction in a concentration-dependent manner. The inhibition was reversed by naloxone. The opioid effect was detected only in the crude base fraction, which was followed by the isolation of five indole alkaloids. Among these alkaloids, 7-hydroxymitragynine showed the most potent opioid effect on the electrically-stimulated contraction (pD(2) = 8.38 +/- 0.12). The potency, calculated using pD(2) values, was 30- and 17-fold higher than that of mitragynine and morphine, respectively. Antagonism of naloxone on concentration-response curves for 7-hydroxymitragynine confirmed its opioid effect. These results suggest that the opioid effect of M. speciosa is mostly based on the activity of 7-hydroxymitragynine.