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洛利内酯,神经系统疾病的一种新治疗选择?从……分离出的一种单萜内酯的体外神经保护和抗炎活性

Loliolide, a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from .

作者信息

Silva Joana, Alves Celso, Martins Alice, Susano Patrícia, Simões Marco, Guedes Miguel, Rehfeldt Stephanie, Pinteus Susete, Gaspar Helena, Rodrigues Américo, Goettert Márcia Ines, Alfonso Amparo, Pedrosa Rui

机构信息

MARE-Marine and Environmental Sciences Centre, Polytechnic of Leiria, 2520-630 Peniche, Portugal.

Department of Pharmacology, Faculty of Veterinary, University of Santiago de Compostela, 27002 Lugo, Spain.

出版信息

Int J Mol Sci. 2021 Feb 14;22(4):1888. doi: 10.3390/ijms22041888.

DOI:10.3390/ijms22041888
PMID:33672866
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7918146/
Abstract

Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed , to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW 264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells' exposure to 6-OHDA in the presence of Loliolide led to an increase of cells' viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and apoptosis, and inhibition of the NF-kB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF-α and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential.

摘要

帕金森病(PD)是全球第二常见的神经退行性疾病,其特征是多巴胺能神经元进行性退化。在没有有效治疗方法的情况下,寻找对抗神经退行性过程的新治疗选择至关重要,这可能源于海洋资源。因此,本研究的目的是评估从绿藻中分离出的单萜内酯洛利内酯对神经毒素6-羟基多巴胺(6-OHDA)介导的SH-SY5Y细胞神经细胞死亡的预防能力及其在RAW 264.7巨噬细胞中的抗炎作用。洛利内酯从乙醚提取物中获得,通过柱色谱法纯化并通过核磁共振光谱鉴定。通过MTT法评估神经保护作用。在洛利内酯存在下,细胞暴露于6-OHDA导致细胞活力提高40%,这种作用是通过线粒体保护、氧化应激状态和细胞凋亡的降低以及NF-κB途径的抑制介导的。此外,洛利内酯还抑制一氧化氮的产生,并抑制TNF-α和IL-6促炎细胞因子的产生。结果表明,洛利内酯可以激发新的神经保护治疗药物的开发,因此,应考虑进行更详细的研究以验证其药理潜力。

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