Butterweck Veronika, Nahrstedt Adolf, Evans Jon, Hufeisen Sandy, Rauser Laura, Savage Jason, Popadak Beth, Ernsberger Paul, Roth Bryan L
Institute of Pharmacology and Toxicology, Westfälische Wilhelms-Universität Muenster, Domagkstrasse 12, 48149 Muenster, Germany.
Psychopharmacology (Berl). 2002 Jul;162(2):193-202. doi: 10.1007/s00213-002-1073-7. Epub 2002 May 9.
Hypericum perforatum L. (St. John's wort; SJW) is one of the leading psychotherapeutic phytomedicines and great effort has been devoted to clarifying its mechanism of action.
We have undertaken a comprehensive analysis of several pure compounds isolated from the crude extract to gain further insight into the molecular actions of various substituents of SJW.
We characterized the in vitro pharmacology of the naphthodianthrones hypericin and pseudohypericin, the phloroglucinol derivative hyperforin, and several flavonoids at 42 biogenic amine receptors and transporters using the resources of the National Institute of Mental Health Psychoactive Drug Screening Program.
The biflavonoid amentoflavone significantly inhibited binding at serotonin (5-HT(1D), 5-HT(2C)), D(3)-dopamine, delta-opiate, and benzodiazepine receptors. The naphthodianthrone hypericin had significant activity at D(3)- and D(4)-dopamine receptors and beta-adrenergic receptors. With the exception of the D(1)-dopamine receptor, the phloroglucinol derivative hyperforin was less active than other SJW constituents tested on all screened receptors.
Our present in vitro data clearly show that several pure substances in SJW are potential CNS psychoactive agents and may contribute to the antidepressant efficacy of the plant in a complex manner. Our data also reveal novel and heretofore unexpected interactions of pure compounds in SJW at a number of GPCRs, transporters, and ion channels. We hypothesize that additive or synergistic actions of different single compounds may be responsible for the antidepressant efficacy of SJW. These results and this general approach may impact our understanding of phytomedicines in general and H. perforatum specifically.
贯叶连翘是主要的用于心理治疗的植物药之一，人们为阐明其作用机制付出了巨大努力。
我们对从粗提取物中分离出的几种纯化合物进行了全面分析，以进一步深入了解贯叶连翘各种取代基的分子作用。
利用美国国立精神卫生研究所精神活性药物筛选项目的资源，我们对萘骈二蒽酮金丝桃素和假金丝桃素、间苯三酚衍生物贯叶连翘素以及几种黄酮类化合物在42种生物胺受体和转运体上的体外药理学特性进行了表征。
双黄酮穗花杉双黄酮显著抑制血清素（5-HT(1D)、5-HT(2C)）、D(3)-多巴胺、δ-阿片样物质和苯二氮䓬受体的结合。萘骈二蒽酮金丝桃素在D(3)-和D(4)-多巴胺受体以及β-肾上腺素能受体上具有显著活性。除D(1)-多巴胺受体外，间苯三酚衍生物贯叶连翘素在所有筛选的受体上的活性均低于其他受试的贯叶连翘成分。
我们目前的体外数据清楚地表明，贯叶连翘中的几种纯物质是潜在的中枢神经系统精神活性药物，可能以复杂的方式促成该植物的抗抑郁功效。我们的数据还揭示了贯叶连翘中纯化合物在许多G蛋白偶联受体、转运体和离子通道上存在新颖且此前未预料到的相互作用。我们推测不同单一化合物的相加或协同作用可能是贯叶连翘抗抑郁功效的原因。这些结果和这种总体方法可能会影响我们对一般植物药尤其是贯叶连翘的理解。
