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心叶山麻杆(Alchornea cordifolia (Schumach. & Thonn.) Mull. Arg.)(大戟科)乙醇提取物对小鼠的抗抑郁样作用:单胺能系统的参与

Antidepressant-like effect of the hydroethanolic leaf extract of Alchornea cordifolia (Schumach. & Thonn.) Mull. Arg. (Euphorbiaceae) in mice: involvement of monoaminergic system.

作者信息

Ishola Ismail O, Agbaje Esther O, Akinleye Moshood O, Ibeh Chris O, Adeyemi Olufunmilayo O

机构信息

Department of Pharmacology, Therapeutics, and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, PMB 12003 Surulere, Lagos, Nigeria.

Department of Pharmacology, Therapeutics, and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, PMB 12003 Surulere, Lagos, Nigeria.

出版信息

J Ethnopharmacol. 2014 Dec 2;158 Pt A:364-72. doi: 10.1016/j.jep.2014.10.008. Epub 2014 Oct 16.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The leaf of Alchornea cordifolia (Euphorbiaceae) is used in traditional African medicine in the treatment of various neurological and psychiatric disorders including depression. Previous studies have shown its potent antidepressant-like effect in the forced swimming test (FST). Hence, this study sought to investigate the involvement of monoaminergic systems in the antidepressant-like effect elicited by hydroethanolic leaf extract of Alchornea cordifolia (HeAC) in the FST.

MATERIALS AND METHODS

HeAC (25-400mg/kg, p.o.) was administered 1h before the FST. To investigate the contribution of monoaminergic systems to antidepressant-like effect, receptors antagonists were injected 15min before oral administration of HeAC (200mg/kg) to mice and 1h thereafter, subjected to FST.

RESULTS

HeAC (200 and 400mg/kg, p.o.) produced dose dependent and significant (P<0.001) antidepressant-like effect, in the FST, without accompanying changes in spontaneous locomotor activities in the open-field test. The anti-immobility effect of HeAC (200mg/kg) in the FST was prevented by pretreatment of mice with SCH 23390 (0.05mg/kg, s.c., a dopamine D1 receptor antagonist), sulpiride (50mg/kg, i.p., a dopamine D2 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., an α2-adrenoceptor antagonist), and GR 127993 (5-HT1B receptor antagonist). Similarly, 3 days intraperitoneal injection of p-chlorophenylalanine (pCPA, 150mg/kg, i.p., an inhibitor of serotonin synthesis) prevented the antidepressant-like effect elicited by HeAC. The combination of subeffective doses of imipramine (5mg/kg, p.o.) or fluoxetine (5mg/kg, p.o.), with HeAC (25mg/kg, p.o., subeffective dose) produced a synergistic antidepressant-like effect in the FST.

CONCLUSION

The hydroethanolic extract of Alchornea cordifolia possesses antidepressant-like effect mediated through interaction with dopamine (D1 and D2), noradrenergic (α1 and α2 adrenoceptors), and serotonergic (5HT1B receptors) systems. Also, the potentiation of the anti-immobility effect of conventional antidepressants (fluoxetine and imipramine) by Alchornea cordifolia suggest potential therapeutic effect in depression.

摘要

民族药理学相关性

心叶山麻杆(大戟科)叶在非洲传统医学中用于治疗包括抑郁症在内的各种神经和精神疾病。先前的研究已表明其在强迫游泳试验(FST)中具有显著的抗抑郁样作用。因此,本研究旨在探讨单胺能系统在FST中的心叶山麻杆水乙醇叶提取物(HeAC)引发的抗抑郁样作用中的参与情况。

材料与方法

在FST前1小时口服给予HeAC(25 - 400mg/kg)。为研究单胺能系统对抗抑郁样作用的贡献,在给小鼠口服HeAC(200mg/kg)前15分钟注射受体拮抗剂,1小时后进行FST。

结果

HeAC(200和400mg/kg,口服)在FST中产生剂量依赖性且显著(P<0.001)的抗抑郁样作用,同时在旷场试验中自发运动活动无伴随变化。用SCH 23390(0.05mg/kg,皮下注射,多巴胺D1受体拮抗剂)、舒必利(50mg/kg,腹腔注射,多巴胺D2受体拮抗剂)、哌唑嗪(1mg/kg,腹腔注射,α1 - 肾上腺素能受体拮抗剂)、育亨宾(1mg/kg,腹腔注射,α2 - 肾上腺素能受体拮抗剂)和GR 127993(5 - HT1B受体拮抗剂)预处理小鼠可阻断HeAC(200mg/kg)在FST中的抗不动作用。同样,连续3天腹腔注射对氯苯丙氨酸(pCPA,150mg/kg,腹腔注射,5 - 羟色胺合成抑制剂)可阻断HeAC引发的抗抑郁样作用。亚有效剂量的丙咪嗪(5mg/kg,口服)或氟西汀(5mg/kg,口服)与HeAC(25mg/kg,口服,亚有效剂量)联合使用在FST中产生协同抗抑郁样作用。

结论

心叶山麻杆水乙醇提取物具有通过与多巴胺(D1和D2)、去甲肾上腺素能(α1和α2肾上腺素能受体)和5 - 羟色胺能(5HT1B受体)系统相互作用介导的抗抑郁样作用。此外,心叶山麻杆增强传统抗抑郁药(氟西汀和丙咪嗪)的抗不动作用表明其在抑郁症中具有潜在治疗作用。

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