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L. 的乙酸乙酯提取物及其生物活性成分伊立替康 B 对 LPS 诱导的小胶质细胞炎症和 MPTP 中毒 PD 样小鼠模型的改善作用。

The Ameliorative Effects of the Ethyl Acetate Extract of L. and Its Bioactive Candidate, Irilin B, on LPS-Induced Microglial Inflammation and MPTP-Intoxicated PD-Like Mouse Model.

机构信息

Department of Applied Life Sciences, Graduate school of Konkuk University, Research Institute of Inflammatory Diseases, Chungju 27478, Republic of Korea.

Research Center, Phyto Corporation, Seoul 08826, Republic of Korea.

出版信息

Oxid Med Cell Longev. 2019 Jul 9;2019:6764756. doi: 10.1155/2019/6764756. eCollection 2019.

DOI:10.1155/2019/6764756
PMID:31379989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6652089/
Abstract

Hyperactivation of microglia, the resident innate immune cells of the central nervous system, exacerbates various neurodegenerative disorders, including Parkinson's disease (PD). Parkinson's disease is generally characterized by a severe loss of dopaminergic neurons in the nigrostriatal pathway, with substantial neuroinflammation and motor deficits. This was experimentally replicated in animal models, using neurotoxins, i.e., LPS (lipopolysaccharides) and MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). L. (SE) has been used as a dietary supplement in Korea and Europe for several years, due to its nutritional and therapeutic value. In this study, we intend to investigate the antineuroinflammatory and anti-PD-like effects of the bioactive fraction/candidate of the SE extract. Initially, we screened various fractions of SE extract using an antioxidant assay. The optimal fraction was investigated for its antineuroinflammatory potential in LPS-stimulated BV-2 microglial cells and anti-PD-like potential in MPTP-intoxicated mice. Subsequently, to identify the potential candidate responsible for the elite therapeutic potential of the optimal fraction, we conducted antioxidant activity-guided isolation and purification; the bioactive candidate was structurally characterized using nuclear magnetic resonance spectroscopy and chromatographic techniques and further investigated for its antioxidative and antineuroinflammatory potential. The results of our study indicate that SE-EA and its bioactive candidate, Irilin B, effectively alleviate the deleterious effect of microglia-mediated neuroinflammation and promote antioxidative effects. Thus, they exhibit potential as therapeutic candidates against neuroinflammatory and oxidative stress-mediated PD-like neurodegenerative complications.

摘要

小胶质细胞的过度激活会加剧各种神经退行性疾病,包括帕金森病(PD)。帕金森病的特征通常是黑质纹状体通路中多巴胺能神经元的严重丧失,伴随着大量的神经炎症和运动缺陷。这在动物模型中通过神经毒素得到了复制,即 LPS(脂多糖)和 MPTP(1-甲基-4-苯基-1,2,3,6-四氢吡啶)。

在韩国和欧洲,L.(SE)已经作为膳食补充剂使用了数年,因为它具有营养价值和治疗价值。在这项研究中,我们旨在研究 SE 提取物的生物活性部分/候选物的抗神经炎症和抗 PD 样作用。最初,我们使用抗氧化测定法筛选了 SE 提取物的各种部分。对最佳部分进行了研究,以评估其在 LPS 刺激的 BV-2 小胶质细胞中的抗神经炎症潜力和在 MPTP 中毒小鼠中的抗 PD 样潜力。随后,为了确定最佳部分的精英治疗潜力的潜在候选物,我们进行了抗氧化活性导向的分离和纯化;使用核磁共振波谱和色谱技术对生物活性候选物进行结构表征,并进一步研究其抗氧化和抗神经炎症潜力。

我们的研究结果表明,SE-EA 及其生物活性候选物 Irilin B 可有效减轻小胶质细胞介导的神经炎症的有害影响,并促进抗氧化作用。因此,它们作为治疗神经炎症和氧化应激介导的 PD 样神经退行性并发症的候选药物具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541d/6652089/072932e68b06/OMCL2019-6764756.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541d/6652089/440d7b9ab22f/OMCL2019-6764756.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541d/6652089/925735de3c40/OMCL2019-6764756.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541d/6652089/991a9f881ceb/OMCL2019-6764756.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541d/6652089/b4d0a3382917/OMCL2019-6764756.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541d/6652089/072932e68b06/OMCL2019-6764756.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541d/6652089/440d7b9ab22f/OMCL2019-6764756.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541d/6652089/925735de3c40/OMCL2019-6764756.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541d/6652089/991a9f881ceb/OMCL2019-6764756.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541d/6652089/b4d0a3382917/OMCL2019-6764756.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541d/6652089/072932e68b06/OMCL2019-6764756.005.jpg

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