Horie Syunji, Koyama Fumi, Takayama Hiromitsu, Ishikawa Hayato, Aimi Norio, Ponglux Dhavadee, Matsumoto Kenjiro, Murayama Toshihiko
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Planta Med. 2005 Mar;71(3):231-6. doi: 10.1055/s-2005-837822.
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.
最近，我们发现帽柱木碱（一种美丽帽柱木的主要成分）具有阿片样激动活性，但其较弱的效力无法解释这种植物的鸦片样作用。在本研究中，对美丽帽柱木叶粗提物进行了生物测定导向的分级分离，以寻找除帽柱木碱之外的强效阿片样激动剂。使用豚鼠回肠电刺激诱导的抽搐收缩来评估阿片样激动活性。美丽帽柱木粗提物以浓度依赖性方式抑制抽搐收缩。这种抑制作用可被纳洛酮逆转。仅在粗碱级分中检测到阿片样作用，随后从中分离出了五种吲哚生物碱。在这些生物碱中，7-羟基帽柱木碱对电刺激收缩表现出最强的阿片样作用（pD(2)=8.38±0.12）。使用pD(2)值计算，其效力分别比帽柱木碱和吗啡高30倍和17倍。纳洛酮对7-羟基帽柱木碱浓度-反应曲线的拮抗作用证实了其阿片样作用。这些结果表明，美丽帽柱木的阿片样作用主要基于7-羟基帽柱木碱的活性。
