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反复的社会挫败应激会加剧脂多糖诱导的小鼠行为缺陷:白金叶树果实提取物通过抗神经炎症、抗氧化和神经化学平衡发挥改善作用。

Repeated social defeat stress exacerbates lipopolysaccharide-induced behavioural deficits in mice: ameliorative role of Chrysophyllum albidum fruit extract through anti-neuroinflammation, antioxidant and neurochemical balance.

作者信息

Ajayi Abayomi M, Ben-Azu Benneth, Ogunkolade Gracious E, Melete John, Oyedele Ayomide T, Umukoro Solomon

机构信息

Neuropharmacology Unit, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Oyo-State, Nigeria.

Department of Pharmacology, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria.

出版信息

Metab Brain Dis. 2022 Oct;37(7):2467-2481. doi: 10.1007/s11011-022-01053-x. Epub 2022 Jul 22.

Abstract

Development of neuropsychiatric disorder is associated with stress-related increase in pro-inflammatory cytokines. Chrysophyllum albidum fruit is an edible tropical fruit containing vitamins and phenolic compounds, well known for their anti-inflammatory and antioxidant activities. This study was designed to investigate the neuroprotective effect of C. albidum fruit extract (CAFE) on stress and lipopolysaccharide (LPS)-induced behavioral and neurochemical impairments in mice. Male Swiss mice were divided into 6 groups (n = 6). Groups 1-3 were orally treated daily for 14 days with normal saline (0.1 mL/10 g), CAFE (100 mg/kg) and Ferulic acid (FA, 10 mg/kg), and left in home cage as controls. Groups 4-6 were treated similarly but subjected to repeated social defeat (RSD) stress using the resident-intruder model from days 1-14. The RSD-animals were injected with LPS (125 µg/kg, i.p) 60 min after each RSD session from days 8-14. Neurobehavioral functions: locomotor, cognitive and anxiety-like behaviors were assessed 24 h after the last treatment. Pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), dopamine, acetylcholinesterase, glutamic acid decarboxylase (GAD), malondialdehyde, nitrites, and reduced glutathione (GSH) were determined in brain tissue. CAFE significantly attenuated RSD and LPS-induced hypolocomotion, cognitive impairment and anxiety-like behavior when compared to the control. Treatment with CAFE also significantly reversed the negative effects of RSD and LPS on pro-inflammatory cytokines, dopamine, acetylcholinesterase, GAD, and oxidative-nitrosative stress levels. The findings clearly indicated that Chrysophyllum albidum fruit demonstrated neuroprotective effects and can play a key role in mitigating against chronic stress and inflammation linked to neuropsychiatric disorders.

摘要

神经精神疾病的发展与促炎细胞因子因应激而增加有关。白金叶树果实是一种可食用的热带水果,含有维生素和酚类化合物,以其抗炎和抗氧化活性而闻名。本研究旨在探讨白金叶树果实提取物(CAFE)对小鼠应激和脂多糖(LPS)诱导的行为及神经化学损伤的神经保护作用。雄性瑞士小鼠分为6组(n = 6)。第1 - 3组每天口服生理盐水(0.1 mL/10 g)、CAFE(100 mg/kg)和阿魏酸(FA,10 mg/kg),持续14天,并作为对照组置于饲养笼中。第4 - 6组给予类似处理,但在第1 - 14天使用定居者 - 入侵者模型使其遭受重复社会挫败(RSD)应激。从第8 - 14天,每次RSD实验后60分钟给RSD组动物腹腔注射LPS(125 μg/kg)。在最后一次处理24小时后评估神经行为功能:运动、认知和焦虑样行为。测定脑组织中的促炎细胞因子(IL - 1β、IL - 6和TNF - α)、多巴胺、乙酰胆碱酯酶、谷氨酸脱羧酶(GAD)、丙二醛、亚硝酸盐和还原型谷胱甘肽(GSH)。与对照组相比,CAFE显著减轻了RSD和LPS诱导的运动减少、认知障碍和焦虑样行为。CAFE处理还显著逆转了RSD和LPS对促炎细胞因子、多巴胺、乙酰胆碱酯酶、GAD以及氧化 - 亚硝化应激水平的负面影响。研究结果清楚地表明,白金叶树果实具有神经保护作用,并且在减轻与神经精神疾病相关的慢性应激和炎症方面可发挥关键作用。

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