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夹竹桃科植物海南巴豆树皮提取物的抗抑郁活性及其对小鼠单胺氧化酶活性的调节作用。

Anti-depressant activity of Erythrina variegata bark extract and regulation of monoamine oxidase activities in mice.

机构信息

Sunandan Divatia School of Science, NMIMS (Deemed-to be) University, 3rd Floor, Bhaidas Sabhagriha Building, Bhaktivedanta Swami Marg, Vile Parle (W), Mumbai, 400 056, India.

出版信息

J Ethnopharmacol. 2020 Feb 10;248:112280. doi: 10.1016/j.jep.2019.112280. Epub 2019 Oct 7.

DOI:10.1016/j.jep.2019.112280
PMID:31600560
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Erythrina variegata, commonly referred to as 'Indian coral tree' belongs to the Fabaceae family. It is a plant native to the coast of India, China and is distributed in tropical and subtropical regions worldwide. In traditional medicine, E. variegata is known to exhibit anxiolytic and anti-convulsant activities and has been used as a nervine sedative. As per the Indian Materia Medica, E. variegata barks have been traditionally known to act on the central nervous system. However, there is a lack of data demonstrating this.

AIM OF THE STUDY

Our study focuses on previously unreported anti-depressant activity of E. variegata bark ethanolic extract (EBE) and determination of its mechanism of action possibly through regulation of monoamine oxidase activity in mouse brain homogenates.

MATERIALS AND METHODS

EBE was characterized using standard protocols for phytochemical analysis, followed by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) analysis. The compounds in EBE (previously reported for anti-depressant activity), were further studied by LC-MS/MS and GC-MS/MS analysis. Anti-depressant activity of EBE (50, 100, 200 and 500 mg/kg) was evaluated in Swiss albino mice using acute and chronic tail suspension test (TST) and forced swim test (FST) models. Furthermore, the possible mechanism of action of EBE was evaluated using the chronic unpredictable mild stress (CUMS) model, wherein inhibitory effects on monoamine oxidase (MAO) A and B were assessed by spectrophotometric-chemical analysis in mouse whole brain homogenates.

RESULTS

EBE showed significant reduction in immobility time periods in both TST (acute: 50, 100 and 200 mg/kg and chronic: 100 and 200 mg/kg) and FST (acute: 200 mg/kg and chronic: 100, 200 and 500 mg/kg) models. Moreover, the locomotor activity test confirmed that acute and chronic administration of EBE did not significantly affect the motor activity of mice. In the CUMS model, EBE when administered alone (100 and 200 mg/kg) and in combination (50, 100 and 200 mg/kg) with escitalopram (15 mg/kg), showed significant reductions in immobility time periods compared to the control group, in the acute FST performed on 22nd day of CUMS. Furthermore, when administered alone (50, 100 and 200 mg/kg), EBE showed significant inhibition in MAO-A and B activities compared to the control group. When used in combination, EBE (50, 100 and 200 mg/kg) showed synergistic action with escitalopram (15 mg/kg), resulting in significantly greater inhibition of MAO-A and B activities, compared to both EBE alone and escitalopram alone. Phytochemical analysis of EBE revealed presence of sugars, steroids, glycosides, alkaloids and tannins. LC-MS, LC-MS/MS, GC-MS and GC-MS/MS analysis identified components in EBE, previously reported for their anti-depressant activity.

CONCLUSIONS

The study thus concluded the anti-depressant like activity of EBE. The study identified components present in EBE that may be responsible for its anti-depressant activity. The possible mechanism of action of EBE was also investigated in the CUMS model, wherein inhibitory effects of EBE on MAO-A and B activities in the mouse brain were demonstrated. Furthermore, the study confirms the traditional use of E. variegata barks in CNS related activities through its anti-depressant like activity.

摘要

民族药理学相关性

“印度珊瑚树”(Erythrina variegata)通常被称为“印度珊瑚树”,属于豆科植物。它是原产于印度、中国海岸的植物,分布于全球热带和亚热带地区。在传统医学中,E. variegata 被认为具有抗焦虑和抗惊厥作用,并被用作神经镇静剂。根据《印度本草》,E. variegata 的树皮传统上被认为对中枢神经系统有作用。然而,目前缺乏证明这一点的数据。

研究目的

本研究重点研究了印度珊瑚树树皮乙醇提取物(EBE)以前未报道的抗抑郁活性,并确定其作用机制可能是通过调节小鼠脑匀浆中单胺氧化酶的活性。

材料和方法

采用标准植物化学分析方案对 EBE 进行了表征,随后进行了液相色谱-质谱联用(LC-MS)和气相色谱-质谱联用(GC-MS)分析。EBE 中的化合物(先前报道具有抗抑郁活性)通过 LC-MS/MS 和 GC-MS/MS 分析进一步研究。采用急性和慢性悬尾试验(TST)和强迫游泳试验(FST)模型,评估了 EBE(50、100、200 和 500mg/kg)对瑞士白化小鼠的抗抑郁活性。此外,还通过慢性不可预测轻度应激(CUMS)模型评估了 EBE 的可能作用机制,通过分光化学分析评估了 EBE 对小鼠全脑匀浆中 MAO-A 和 MAO-B 的抑制作用。

结果

EBE 在 TST(急性:50、100 和 200mg/kg 和慢性:100 和 200mg/kg)和 FST(急性:200mg/kg 和慢性:100、200 和 500mg/kg)模型中均显著减少了不动时间。此外,运动活性测试证实,EBE 的急性和慢性给药并未显著影响小鼠的运动活性。在 CUMS 模型中,EBE 单独给药(100 和 200mg/kg)和与依地普仑(15mg/kg)联合给药(50、100 和 200mg/kg)时,与对照组相比,在第 22 天进行的急性 FST 中,不动时间明显减少。此外,EBE 单独给药(50、100 和 200mg/kg)时,与对照组相比,MAO-A 和 MAO-B 活性显著抑制。联合给药时,EBE(50、100 和 200mg/kg)与依地普仑(15mg/kg)联合使用表现出协同作用,与 EBE 单独给药和依地普仑单独给药相比,MAO-A 和 MAO-B 活性的抑制作用明显更大。EBE 的植物化学分析显示存在糖、类固醇、糖苷、生物碱和单宁。LC-MS、LC-MS/MS、GC-MS 和 GC-MS/MS 分析鉴定了 EBE 中的成分,这些成分先前被报道具有抗抑郁活性。

结论

因此,该研究得出了 EBE 具有抗抑郁样活性的结论。该研究确定了 EBE 中可能负责其抗抑郁活性的成分。还在 CUMS 模型中研究了 EBE 的可能作用机制,证明了 EBE 对小鼠大脑中 MAO-A 和 MAO-B 活性的抑制作用。此外,该研究通过其抗抑郁样活性证实了 E. variegata 树皮在中枢神经系统相关活动中的传统用途。

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