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牛蒡子苷元对鱼藤酮诱导的神经炎症和氧化应激的神经保护作用。

Neuroprotective effect of arctigenin against neuroinflammation and oxidative stress induced by rotenone.

作者信息

Zhang Na, Dou Deqiang, Ran Xiaoku, Kang Tingguo

机构信息

College of Pharmacy, Liaoning University of Traditional Chinese Medicine 77 Life One Road, DD Port Dalian 116600 PR China

出版信息

RSC Adv. 2018 Jan 10;8(5):2280-2292. doi: 10.1039/c7ra10906g. eCollection 2018 Jan 9.

Abstract

: the present study was to investigate the neuroprotective effect of arctigenin, the major active component of a traditional Chinese medicine "Arctii Fructus", against PD in a rat model induced by rotenone. : in the present study, rotenone was injected subcutaneously in the backs of rats to mimic the progressive neurodegenerative nature of PD and arctigenin was administered. Behavioral analyses including a grid test, bar test and open-field test were used to evaluate motor activities and behavioral movement abilities. Energy metabolism indexes including oxygen consumption, carbon dioxide production, heat production and energy expenditure were measured a TSE phenoMaster/LabMaster animal monitoring system. Immunohistochemistry was performed to detect the staining of TH and the expression of α-synuclein in substantia nigra (SN). The effect of arctigenin on oxidative stress was evaluated by the levels of GSH and MDA, and activities of SOD and GSH-Px. The levels of pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α, IFN-γ and PGE2, the expression of Iba-1 and GFAP, and the impression of inflammatory mediators such as COX-2 and NF-κB in the SN were measured to evaluate the effect on the inflammation of SN area induced by rotenone. : compared with the ROT group, the deadlock time of rats treated with arctigenin was significantly shortened and the score of locomotor activity increased in the behavioral test; the number of TH positive DA neurons of the arctigenin treated group was increased and α-synuclein immunopositive was decreased; the level of GSH and activities of SOD and GSH-Px in the arctigenin-treated group were significantly increased; arctigenin administration induced a significant decrease in the MDA level; arctigenin also significantly decreased the levels of IL-6, IL-1β, TNF-α, IFN-γ and PGE2 and reduced the impression of COX-2 and NF-κB in SN; treatment with arctigenin decreased microglia and astrocyte activation evidenced by the reduced expression of Iba-1 and GFAP. : the findings demonstrated that arctigenin can improve the behavior changes of PD rats and the damage of DA neurons. The oxidative stress and inflammation involved in the pathogenesis of PD and arctigenin may protect DA neurons through its potent antioxidant and anti-inflammatory activities.

摘要

本研究旨在探讨中药“牛蒡子”的主要活性成分牛蒡子苷元对鱼藤酮诱导的大鼠帕金森病(PD)模型的神经保护作用。在本研究中,将鱼藤酮皮下注射到大鼠背部以模拟PD的进行性神经退行性本质,并给予牛蒡子苷元。采用包括网格试验、杆试验和旷场试验在内的行为分析来评估运动活动和行为运动能力。使用TSE phenoMaster/LabMaster动物监测系统测量包括耗氧量、二氧化碳产生量、产热量和能量消耗在内的能量代谢指标。进行免疫组织化学检测黑质(SN)中酪氨酸羟化酶(TH)的染色和α-突触核蛋白的表达。通过谷胱甘肽(GSH)和丙二醛(MDA)水平以及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性评估牛蒡子苷元对氧化应激的影响。测量SN中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)和前列腺素E2(PGE2)等促炎细胞因子的水平、离子钙结合衔接分子1(Iba-1)和胶质纤维酸性蛋白(GFAP)的表达以及环氧化酶-2(COX-2)和核因子κB(NF-κB)等炎症介质的印记,以评估对鱼藤酮诱导的SN区域炎症的影响。与鱼藤酮组相比,牛蒡子苷元治疗组大鼠在行为测试中的僵住时间显著缩短,运动活动评分增加;牛蒡子苷元治疗组TH阳性多巴胺能神经元数量增加,α-突触核蛋白免疫阳性减少;牛蒡子苷元治疗组GSH水平以及SOD和GSH-Px活性显著增加;给予牛蒡子苷元导致MDA水平显著降低;牛蒡子苷元还显著降低了IL-6、IL-1β、TNF-α、IFN-γ和PGE2的水平,并减少了SN中COX-2和NF-κB的印记;牛蒡子苷元治疗减少了小胶质细胞和星形胶质细胞的活化,这通过Iba-1和GFAP表达的降低得以证明。研究结果表明,牛蒡子苷元可以改善PD大鼠的行为变化和多巴胺能神经元的损伤。PD发病机制中涉及的氧化应激和炎症,而牛蒡子苷元可能通过其强大的抗氧化和抗炎活性保护多巴胺能神经元。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73ab/9077403/97294a0fa576/c7ra10906g-f1.jpg

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