Franklin M, Cowen P J
University of Oxford Department of Psychiatry, Warneford Hospital, UK.
Pharmacopsychiatry. 2001 Jul;34 Suppl 1:S29-37. doi: 10.1055/s-2001-15443.
We have studied the effect of acute and sub-chronic treatments of a formulation of a methanolic extract of hypericum perforatum (HP, also known as St John's wort) on plasma hormones and brain neurotransmitters in healthy human volunteers and rats. Also studied were the effects of equivalent acute doses of two constituents of HP (with respect to LI 160 extract), hypericin and hyperforin in rats. In acute treatment studies in normal volunteers subjects received 9 tablets of the finished product Jarsin 300 and placebo in the pilot study (unblinded) and in the main study (a double blind, balanced order, cross-over design). Results in normal volunteer studies show that HP caused significant increases of salivary cortisol and plasma growth hormone (GH) whereas it decreased plasma prolactin versus placebo. Plasma hormone levels were associated with a rise in plasma hyperforin but not with hypericin, however no significant correlation was found. In the animal studies, acute treatment with LI 160, hyperforin and hypericin all caused significant increases in plasma corticosterone. This was associated with significant increases in brain cortical tissue 5-HT content. The corticosterone responses were attenuated by the 5-HT2 receptor antagonist, ketanserin but not by the 5-HT1A antagonist, WAY-100635. This suggests that the corticosterone responses may be mediated via a 5-HT2 mechanism of action. When sub-chronic and acute treatment using two different doses of LI 160 were compared, plasma corticosterone level were significantly decreased. Thus suggesting a down-regulation or desensitisation of post-synaptic 5-HT2 receptors. Plasma prolactin was significantly reduced by acute treatment with LI 160 and hyperforin treatment but not by hypericin. This was associated with a concomitant rise in brain cortical tissue DA. Both LI 160 and hyperforin treatments decreased the plasma prolactin responses to the DA antagonist, haloperidol, suggesting that this may be associated with a DA-mediated mechanisn of action. When acute and sub-chronic treatments were compared, plasma prolactin responses were increased in the sub-chronically treated animals. The studies when taken together suggest that the LI 160 extract may effect plasma hormonal changes via both 5-HT and DA-mediated mechanisms but do not involve noradrenaline (NA). The data also suggests that hyperforin may be more important than hypericin for effecting these changes following acute treatment. Further studies investigating both acute and sub-chronic effects of these compounds are necessary.
我们研究了贯叶连翘（HP，也称为圣约翰草）甲醇提取物制剂的急性和亚慢性处理对健康人类志愿者和大鼠血浆激素及脑神经递质的影响。还研究了HP的两种成分（相对于LI 160提取物）金丝桃素和贯叶连翘素在大鼠中等效急性剂量的作用。在正常志愿者的急性治疗研究中，受试者在预试验（非盲法）和主要研究（双盲、平衡顺序、交叉设计）中分别服用了9片成品Jarsin 300和安慰剂。正常志愿者研究结果表明，与安慰剂相比，HP可显著提高唾液皮质醇和血浆生长激素（GH）水平，而降低血浆催乳素水平。血浆激素水平与血浆贯叶连翘素升高有关，但与金丝桃素无关，然而未发现显著相关性。在动物研究中，LI 160、贯叶连翘素和金丝桃素的急性处理均导致血浆皮质酮显著升高。这与脑皮质组织5-羟色胺（5-HT）含量显著增加有关。5-HT2受体拮抗剂酮色林可减弱皮质酮反应，但5-HT1A拮抗剂WAY-100635则无此作用。这表明皮质酮反应可能通过5-HT2作用机制介导。当比较使用两种不同剂量LI 160的亚慢性和急性处理时，血浆皮质酮水平显著降低。因此提示突触后5-HT2受体下调或脱敏。LI 160和贯叶连翘素的急性处理可显著降低血浆催乳素水平，但金丝桃素则无此作用。这与脑皮质组织多巴胺（DA）同时升高有关。LI 160和贯叶连翘素处理均降低了血浆催乳素对DA拮抗剂氟哌啶醇的反应，提示这可能与DA介导的作用机制有关。当比较急性和亚慢性处理时，亚慢性处理动物的血浆催乳素反应增加。综合这些研究表明，LI 160提取物可能通过5-HT和DA介导的机制影响血浆激素变化，但不涉及去甲肾上腺素（NA）。数据还表明，在急性处理后，贯叶连翘素可能比金丝桃素对产生这些变化更为重要。有必要进一步研究这些化合物的急性和亚慢性作用。
