大黄素对行为和应激轴反应表现出抗抑郁样作用：与 5-羟色胺能有关的证据。
Purpurin exerted antidepressant-like effects on behavior and stress axis reactivity: evidence of serotonergic engagement.
机构信息
Department of Neurology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei Province, China.
Department of Vasculocardiology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei Province, China.
出版信息
Psychopharmacology (Berl). 2020 Mar;237(3):887-899. doi: 10.1007/s00213-019-05422-w. Epub 2020 Jan 3.
RATIONALE AND OBJECTIVES
Major depression represents a significant public health problem worldwide, and effective regimen is lacking. The present study investigated the antidepressant-like effects of purpurin, a natural anthraquinone compound from Rubia tinctorum L., and explored the underlying mechanism(s).
METHODS
Forced swim test (FST) and tail suspension test (TST) were used to assess antidepressant-like effects of purpurin in mice. Effects of purpurin on neuroendocrine responsivity were evaluated at the level of corticosterone and ACTH following acute restraint stress and intracerebroventricular injection of corticotrophin-releasing-factor (CRF). Serotonergic mechanisms underlying purpurin antidepressant effect were explored using biochemical, neurochemical, and pharmacological paradigms.
RESULTS
Chronic purpurin treatment exerted in mice dose-dependently antidepressant-like effects on behavior and stress axis reactivity (n = 9-11 per group). The purpurin-triggered antidepressant-like effects are serotonergically dependent, since purpurin-treated mice showed escalated levels of brain serotonin and suppressed monoamine oxidase (MAO) activity (n = 8-11 per group). Consistently, chemical depletion of brain serotonin by p-chlorophenylalanine (PCPA) abolished the antidepressant-like effects of purpurin on behavior and stress axis responsivity (n = 9-10 per group). Moreover, the antidepressant effect by purpurin was preferentially counteracted by 1A-selective 5-HT receptor antagonist WAY-100635, but potentiated by 1A-selective agonist 8-OH-DPAT and sub-effective dose of serotonergic antidepressant fluoxetine (n = 9-11 per group), suggesting a crucial role for 5-HT related serotonergic system in mediating such purpurin antidepressant effect.
CONCLUSION
We have revealed the antidepressant-like effects of purpurin on both behavior and stress axis reactivity in mice, with serotonergic system that preferentially couples with 5-HT receptors being critically engaged.
背景与目的
重度抑郁症是全球范围内一个重大的公共卫生问题，但目前仍缺乏有效的治疗方法。本研究旨在探讨天然蒽醌化合物茜草素（来源于茜草 Rubia tinctorum L.）的抗抑郁样作用及其潜在机制。
方法
采用强迫游泳试验（FST）和悬尾试验（TST）评估茜草素对小鼠的抗抑郁样作用。采用急性束缚应激和脑室内注射促肾上腺皮质激素释放因子（CRF）的方法，评估茜草素对神经内分泌反应的影响，检测皮质酮和促肾上腺皮质激素（ACTH）的水平。采用生化、神经化学和药理学方法研究茜草素抗抑郁作用的 5-羟色胺能机制。
结果
茜草素在小鼠体内具有剂量依赖性的抗抑郁样作用，可改善行为和应激轴反应（每组 9-11 只）。茜草素触发的抗抑郁样作用依赖于 5-羟色胺能系统，因为茜草素处理的小鼠表现出脑内 5-羟色胺水平升高和单胺氧化酶（MAO）活性受抑制（每组 8-11 只）。同样，用对氯苯丙氨酸（PCPA）化学耗竭脑内 5-羟色胺可消除茜草素对行为和应激轴反应的抗抑郁样作用（每组 9-10 只）。此外，1A 选择性 5-羟色胺受体拮抗剂 WAY-100635优先拮抗茜草素的抗抑郁作用，而 1A 选择性激动剂 8-OH-DPAT 和低有效剂量的 5-羟色胺再摄取抑制剂氟西汀则增强茜草素的抗抑郁作用（每组 9-11 只），提示 5-羟色胺相关 5-羟色胺能系统在介导茜草素的抗抑郁作用中起着关键作用。
结论
本研究揭示了茜草素对小鼠行为和应激轴反应均具有抗抑郁样作用，其作用机制可能与 5-羟色胺能系统优先与 5-羟色胺受体偶联有关。
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