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猴面包树甲醇茎皮提取物改善慢性不可预测轻度应激诱导的抑郁样行为:下丘脑-垂体-肾上腺轴、脑源性神经营养因子和应激生物标志物途径的参与

Methanol stem bark extract of Adansonia digitata ameliorates chronic unpredictable mild stress-induced depression-like behavior: Involvement of the HPA axis, BDNF, and stress biomarkers pathways.

作者信息

Shehu Aishatu, Magaji Mohammed Garba, Yau Jamilu, Ahmed Abubakar

机构信息

Department of Pharmacology and Therapeutics, Ahmadu Bello University, PMB 1045, Zaria, Nigeria, Phone: + 234 803 6028298.

Department of Pharmacology and Therapeutics, Ahmadu Bello University, Zaria, Nigeria.

出版信息

J Basic Clin Physiol Pharmacol. 2019 Apr 24;30(3):jbcpp-2018-0153. doi: 10.1515/jbcpp-2018-0153.

DOI:10.1515/jbcpp-2018-0153
PMID:31017871
Abstract

Background Adansonia digitata L. (Malvaceae) is used locally in the management of depressive illnesses, and its antidepressant-like effect has been previously reported. The present study was aimed at determining the effect of the methanol extract of the stem bark of A. digitata (MEAD) on chronic unpredictable mild stress (CUMS) and the possible mechanism responsible for its antidepressant activity. Methods Acute toxicity of MEAD was determined using the OECD guideline 420. The CUMS model was used to induce depression, and behavioral tests such as sucrose preference test (SPT), open field test (OFT), novel-object recognition test (NORT), and tail suspension test (TST) were carried out in mice. The concentrations of plasma cortisol and brain-derived neurotrophic factor (BDNF) protein in the brain were assessed using enzyme-linked immunosorbent assay kits. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were assessed using colorimetric methods. Results The LD50 was established to be ≥5000 mg/kg. On CUMS-induced depression, MEAD significantly (p ≤ 0.05) and dose dependently reversed the weight loss, increased the line-crossing activity in OFT, increased sucrose consumption in SPT, decreased the duration of immobility in TST, and increased the novelty exploration time in NORT. The MEAD extract significantly (p ≤ 0.05) and dose dependently increased the levels of BDNF, decreased the levels of plasma cortisol, increased the levels of total SOD activity, and decreased the levels of plasma MDA. Conclusion Our findings show that MEAD ameliorates CUMS-induced depressive-like behavior and its effect is possibly mediated via the neuroendocrine, neurotrophic, and oxidative stress pathways.

摘要

背景 猴面包树(锦葵科)在当地用于治疗抑郁症,此前已有其抗抑郁样作用的报道。本研究旨在确定猴面包树茎皮甲醇提取物(MEAD)对慢性不可预测轻度应激(CUMS)的影响及其抗抑郁活性的可能机制。方法 使用经合组织准则420确定MEAD的急性毒性。采用CUMS模型诱导抑郁,并在小鼠中进行行为测试,如蔗糖偏好试验(SPT)、旷场试验(OFT)、新物体识别试验(NORT)和悬尾试验(TST)。使用酶联免疫吸附测定试剂盒评估血浆皮质醇浓度和脑中脑源性神经营养因子(BDNF)蛋白水平。使用比色法评估超氧化物歧化酶(SOD)和丙二醛(MDA)水平。结果 确定LD50≥5000 mg/kg。对于CUMS诱导的抑郁,MEAD显著(p≤0.05)且剂量依赖性地逆转体重减轻,增加OFT中的穿线活动,增加SPT中的蔗糖消耗,减少TST中的不动持续时间,并增加NORT中的新奇探索时间。MEAD提取物显著(p≤0.05)且剂量依赖性地增加BDNF水平,降低血浆皮质醇水平,增加总SOD活性水平,并降低血浆MDA水平。结论 我们的研究结果表明,MEAD可改善CUMS诱导的抑郁样行为,其作用可能通过神经内分泌、神经营养和氧化应激途径介导。

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