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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Potential of novel phytoecdysteroids isolated from Vitex doniana in the treatment depression: Involvement of monoaminergic systems
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Potential of novel phytoecdysteroids isolated from Vitex doniana in the treatment depression: Involvement of monoaminergic systems

机译：从唐胶荆中分离出的新型植物蜕皮激素在治疗抑郁症中的潜力：单胺能系统的参与

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Vitex doniana Sweet (Verbanaceae) is used in traditional African medicine for the treatment of neurological disorders including depression. In our previous studies, three new phytoecdysteroids were isolated from methanol stem bark extract of V. doniana (VD) (11 beta-hydroxy-20-deoxyshidasterone, 21-hydroxyshidasterone, and 2,3-acetonide-24-hydroxyecdysone) along with known ecdysteroids. This study was designed to investigate antidepressant-like effect of VD and the isolated phytoecdysteroids in behavioral models of despair, forced-swim test (FST) and tail-suspension test (TST) in mice. VD (100 and 200 mg/kg, p.o.) treatment reduced (P < 0.05) the duration of immobility in both tests without affecting the locomotor activity and exploratory behavior as Observed in the open field test. Similarly, 21-hydroxyshidasterone, 11 beta-hydroxy-20-deoxyshidasterone, ajugasterone and 24-hydroxyecdysone acute oral treatments significantly reduced immobility time with peak effect at 10 mg/kg, which was similar to the effect of conventional antidepressants (imipramine and fluoxetine) in the FST. Conversely, pretreatment of mice with yohimbine (1 mg/kg, i.p., alpha(2)-adrenoceptor antagonist), ketanserin (5 mg/kg, i.p., 5-HT2A/2C receptor antagonist) or sulpiride (dopamine D-2 receptor antagonist) prevented the antidepressant-like effect of 21-hydroxyshidasterone while the effects of 11 beta-hydroxy-20-deoxyshidasterone and 24-hydroxyecdysone were blocked by yohimbine or ketanserin in the FST. Moreover, the anti-immobility effect elicited by ajugasterone was prevented by prazosin (62.5 mu g/kg, i.p., alpha(1)-adrenoceptor antagonist) pretreatment. Our findings demonstrated that V. doniana and its phytoecdysteroids constituents elicited antidepressant-like effect in behavioral paradigm of despair. Furthermore, 21-hydroxyshidasterone produces its antidepressant-like effect through interaction with alpha(2)-adrenoceptor, 5-HT2A/2C receptor and dopamine D-2-receptors but 11 beta-hydroxy-20-deoxyshidasterone and 24-hydroxyecdysone effects depend on interaction with alpha(2)-adrenoceptor and 5-HT2A/2C receptors while ajugasterone produces its action through interaction with post-synaptic alpha(1)-adrenoceptors. Thus, phytoecdysteroids could play a pivotal role in the treatment of major depression. (C) 2014 Elsevier Inc. All rights reserved.
机译：Vitex doniana Sweet（马鞭草科）被用于非洲传统医学中，用于治疗包括抑郁症在内的神经系统疾病。在我们以前的研究中，从多虫弧菌（VD）的甲醇茎皮提取物中分离出了三种新的植物蜕皮激素（11β-羟基-20-脱氧Shidasterone，21-羟基Shidasterone和2,3-acetonide-24-hydroxyecdysone）以及已知的蜕皮类固醇。本研究旨在研究VD和分离的植物蜕皮激素在小鼠绝望，强迫游泳试验（FST）和尾部悬吊试验（TST）行为模型中的抗抑郁样作用。 VD（100和200 mg / kg，p.o.）处理在两种测试中均减少（P <0.05）固定的持续时间，而不会影响运动能力和探索行为，如在野外测试中观察到的那样。同样，21-羟基紫杉甾酮，11β-羟基-20-脱氧紫杉甾酮，紫杉甾酮和24-羟基蜕皮激素的急性口服治疗可显着降低固定时间，峰值作用为10 mg / kg，这与常规抗抑郁药（丙咪嗪和氟西汀）的作用相似。在FST中。相反，用育亨宾（1 mg / kg，腹膜内注射，α（2）-肾上腺素能受体拮抗剂），酮色林（5 mg / kg，腹膜内注射，5-HT2A / 2C受体拮抗剂）或舒必利（多巴胺D-2受体拮抗剂）预处理小鼠）阻止了21-羟基Shidasterone的抗抑郁样作用，而FST中的育亨宾或ketanserin阻止了11β-羟基-20-deoxyshidasterone和24-hydroxyecdysone的作用。此外，用哌唑嗪（62.5μg/ kg，腹膜内注射α（1）-肾上腺素能受体拮抗剂）预处理可防止由金刚烷酮引起的抗固定作用。我们的发现表明，唐纳弧菌及其植物蜕皮激素成分在绝望的行为范式中引发了抗抑郁样作用。此外，21-羟基shidasterone通过与alpha（2）-肾上腺素受体，5-HT2A / 2C受体和多巴胺D-2-受体相互作用而产生其抗抑郁样作用，但11β-羟基-20-deoxyshidasterone和24-hydroxyecdysone的作用取决于与α（2）-肾上腺素受体和5-HT2A / 2C受体的相互作用，而ajugasterone通过与突触后的α（1）-肾上腺素受体的相互作用产生其作用。因此，植物蜕皮激素可能在重度抑郁症的治疗中起关键作用。 （C）2014 Elsevier Inc.保留所有权利。

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