急性剂量范围评估南非钩麻（Zembrin®）与依地普仑（Escitalopram）在弗林德斯敏感大鼠中抗抑郁特性的比较。
An acute dose-ranging evaluation of the antidepressant properties of Sceletium tortuosum (Zembrin®) versus escitalopram in the Flinders Sensitive Line rat.
机构信息
Center of Excellence for Pharmaceutical Sciences (Pharmacen), North West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa; SAMRC Herbal Drugs Research Unit, Faculty of Science, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa.
出版信息
J Ethnopharmacol. 2022 Feb 10;284:114550. doi: 10.1016/j.jep.2021.114550. Epub 2021 Aug 25.
ETHNOPHARMACOLOGICAL RELEVANCE
Sceletium tortuosum (L.) N.E.Br. (ST) has been used by the Khoisan people of South Africa as a mood elevator. Its various pharmacological mechanisms of action suggest distinct potential as an antidepressant. Clinical studies in healthy individuals suggest beneficial effects on mood, cognition, and anxiety.
AIM OF THE STUDY
To obtain a chromatographic fingerprint of a standardized extract of S. tortuosum (Zembrin®), and to evaluate the acute antidepressant-like properties of Zembrin® versus the reference antidepressant, escitalopram, in the Flinders Sensitive Line (FSL) rat, a genetic rodent model of depression.
MATERIALS AND METHODS
The chemical profile of Zembrin® was determined by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) chromatogram method using alkaloid standards. Twelve saline treated FSL and six Flinders Resistant Line (FRL) control rats were used to confirm face validity of the FSL model using the forced swim test (FST). Thereafter, FSL rats (n = 10) received either 5, 10, 25, 50 or 100 mg/kg of Zembrin®, or 5, 10 or 20 mg/kg escitalopram oxalate (ESC), both via oral gavage, and subjected to the open field test (OFT) and FST.
RESULTS
Four main ST alkaloids were identified and quantified in Zembrin® viz. mesembrenone, mesembrenol, mesembrine, and mesembranol (47.9%, 32%, 13.2%, and 6.8% of the total alkaloids, respectively). FSL rats showed significantly decreased swimming and climbing (coping) behaviours, and significantly increased immobility (despair), versus FRL controls. ESC 5 mg/kg and Zembrin® 25 mg/kg and 50 mg/kg showed significant dose-dependent reversal of immobility in FSL rats and variable effects on coping behaviours. Zembrin® 50 mg/kg was the most effective antidepressant dose, showing equivalence to ESC 5.
CONCLUSIONS
Zembrin® (25 and 50 mg/kg) and ESC (5 mg/kg) are effective antidepressants after acute treatment in the FST, as assessed in FSL rats. Moreover, Zembrin® 50 mg/kg proved equivalent to ESC 5. Further long-term bio-behavioural studies on the antidepressant properties of Zembrin® are warranted.
民族药理学相关性
南非霍萨人曾将扭蒴苣苔（L.）N.E.Br.（简称 ST）用作情绪提升剂。其各种药理作用机制表明，它具有明显的抗抑郁作用。在健康个体中的临床研究表明，其对情绪、认知和焦虑有益处。
研究目的
获得扭蒴苣苔（Zembrin®）标准化提取物的色谱指纹图谱，并评估 Zembrin®与参考抗抑郁药依地普仑（ESC）在弗林德斯敏感系（FSL）大鼠中的急性抗抑郁样特性，FSL 大鼠是一种抑郁的遗传啮齿动物模型。
材料与方法
采用生物碱标准的超高效液相色谱-质谱联用（UPLC-MS）色谱法确定 Zembrin®的化学特征。用 12 只生理盐水处理的 FSL 和 6 只弗林德斯抗性系（FRL）对照大鼠进行强迫游泳试验（FST），以确认 FSL 模型的表面效度。之后，将 FSL 大鼠（n=10）分别给予 5、10、25、50 或 100mg/kg 的 Zembrin®，或 5、10 或 20mg/kg 的依地普仑草酸（ESC），均通过口服灌胃，然后进行旷场试验（OFT）和 FST。
结果
在 Zembrin®中鉴定和定量了 4 种主要的 ST 生物碱，分别为 mesembrenone、mesembrenol、mesembrine 和 mesembranol（分别占总生物碱的 47.9%、32%、13.2%和 6.8%）。与 FRL 对照相比，FSL 大鼠表现出游泳和攀爬（应对）行为明显减少，不动（绝望）行为明显增加。ESC 5mg/kg 和 Zembrin®25mg/kg 和 50mg/kg 显示出剂量依赖性逆转 FSL 大鼠的不动行为，以及对应对行为的可变影响。Zembrin®50mg/kg 是最有效的抗抑郁剂量，与 ESC 5mg/kg 等效。
结论
在 FSL 大鼠中，急性给予 Zembrin®（25 和 50mg/kg）和 ESC（5mg/kg）后，FST 评估显示它们是有效的抗抑郁药。此外，Zembrin®50mg/kg 与 ESC 5mg/kg 等效。需要进一步进行长期的 Zembrin®抗抑郁作用的生物行为学研究。
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