Misane I, Ogren S O
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Pharmacopsychiatry. 2001 Jul;34 Suppl 1:S89-97. doi: 10.1055/s-2001-15449.
Along with traditional pharmacotherapies, extracts of Hypericum perforatum L. (St. John's wort) are used in the treatment of mild to moderately severe depression. Hypericum is a nonspecific inhibitor of the neuronal uptake of monoamines (serotonin, 5-HT; noradrenaline, NA; dopamine, DA) as well as GABA and glutamate. Hypericum extracts have been shown to be active in several different "animal models for antidepressant drugs". As one of a large number of chemical constituents, the phoroglucinol derivative hyperforin might be an important "antidepressant component" of hypericum. However, the exact role of neurochemical mechanisms underlying in vivo actions of hypericum and hyperforin are not well defined. In the present study, we compared the effects of hypericum, hyperforin and hyperforin-free hypericum and the three conventional antidepressants paroxetine, imipramine and desipramine using the passive avoidance (PA) task in the rat. The 5-HT-releasing compound p-chloroamphetamine (PCA), which operates through the 5-HT neuronal transporter, was used to reveal the potential in vivo effects on 5-HT uptake mechanisms. To examine the ability of the test-compounds to enhance noradrenaline (NA) transmission in vivo, subeffective doses of scopolamine were used. Taken together, our results suggest that (1) hypericum given at high doses can probably affect the neuronal 5-HT uptake mechanisms in a manner more reminiscent of TCAs than SSRIs; (2) similar to TCAs and SSRIs, hypericum and hyperforin are active in the scopolamine test. Hyperforin appears to play a major role in the action of hypericum in this model. Both 5-HT and NA might concomitantly contribute to the effects of different antidepressants in the "low-dose scopolamine" model; (3) hypericum might enhance both 5-HT and NA transmission in forebrain limbic brain circuits important for mood control, which could underly its antidepressant effects. However, the relative contribution of different constituents and exact mechanisms of action require further evaluation.
除了传统药物疗法外，贯叶连翘提取物（圣约翰草）还用于治疗轻度至中度严重抑郁症。贯叶连翘是单胺（血清素、5-羟色胺；去甲肾上腺素、NA；多巴胺、DA）以及GABA和谷氨酸神经元摄取的非特异性抑制剂。贯叶连翘提取物已被证明在几种不同的“抗抑郁药物动物模型”中具有活性。作为大量化学成分之一，间苯三酚衍生物金丝桃素可能是贯叶连翘的一种重要“抗抑郁成分”。然而，贯叶连翘和金丝桃素体内作用的神经化学机制的确切作用尚未明确界定。在本研究中，我们使用大鼠被动回避（PA）任务比较了贯叶连翘、金丝桃素和不含金丝桃素的贯叶连翘以及三种传统抗抑郁药帕罗西汀、丙咪嗪和地昔帕明的作用。通过5-羟色胺神经元转运体起作用的5-羟色胺释放化合物对氯苯丙胺（PCA）用于揭示对5-羟色胺摄取机制的潜在体内作用。为了检查受试化合物在体内增强去甲肾上腺素（NA）传递的能力，使用了亚有效剂量的东莨菪碱。综上所述，我们的结果表明：（1）高剂量给予贯叶连翘可能以比选择性5-羟色胺再摄取抑制剂（SSRI）更类似于三环类抗抑郁药（TCA）的方式影响神经元5-羟色胺摄取机制；（2）与TCA和SSRI类似，贯叶连翘和金丝桃素在东莨菪碱试验中具有活性。在该模型中，金丝桃素似乎在贯叶连翘的作用中起主要作用。5-羟色胺和NA可能同时促成不同抗抑郁药在“低剂量东莨菪碱”模型中的作用；（3）贯叶连翘可能增强对情绪控制很重要的前脑边缘脑回路中的5-羟色胺和NA传递，这可能是其抗抑郁作用的基础。然而，不同成分的相对贡献和确切作用机制需要进一步评估。
