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用鱼藤酮诱导的帕金森病小鼠模型研究长梗鸡眼草叶中富含环烯醚萜类化合物的部分的化学成分及其可能的神经保护作用。

Chemical composition and studying the possible neuroprotective effect of iridoids-rich fraction from Pentas lanceolata leaves using rotenone model of Parkinson's disease in mice.

机构信息

Pharmacognosy Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El Bohouth St. (Former El Tahrir St.), Dokki, 12622, Giza, Egypt.

Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El Bohouth St. (Former El Tahrir St.), Dokki, 12622, Giza, Egypt.

出版信息

Inflammopharmacology. 2024 Dec;32(6):3953-3971. doi: 10.1007/s10787-024-01509-9. Epub 2024 Jul 4.

DOI:10.1007/s10787-024-01509-9
PMID:38963536
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11550285/
Abstract

Parkinsonism is an age-related neurodegenerative illness that affects motor coordination leading to loss of dopaminergic neurons. Many medications are used for the treatment of Parkinson's disease but are only symptomatic and have a limited effect on the progression of this ailment. Therefore, bioactive compounds which derived from plants have been examined for their ability to improve the neuronal damage and cell death happened in parkinsonian patients. In this study the iridoids-rich fraction isolated from Pentas lanceolata (PIRF) leaves was investigated for its phytoconstituents. Seven iridoids (1-7) and one flavonol diglycoside (8) were isolated, and their chemical structures were achieved by H and C nuclear magnetic resonance and ESI-MS spectral data. Compound 1 (6β,7β-epoxy-8-epi-splendoside) and 5 (gaertneroside) were isolated for the first time from Pentas genus as well as compound 8 (kaempferol-3-O-robinobioside). The current study aims to investigate the possible anti-parkinsonian effect of PIRF using a rotenone model of Parkinsonism in mice. Behavioural tests (wirehanging, stair and wooden-walking tests) were done to examine the motor coordination in mice after treatment. Biochemical and histopathological examinations for brain striatum in different groups were also evaluated. Results revealed that rotenone-treated mice had poor motor functions described by depletion of dopamine and Ach levels, a significant increase in proinflammatory cytokines, IL-1B, TNF-α and Mcp-1 and oxidative biomarkers with subsequent reduction in antioxidant mediators. Disorganization of striatum, degenerated neurocytes, slight vacuolation, shrunken neurons with pyknotic nuclei and apoptotic cells are displayed by histopathological examinations. Treatment with PIRF ameliorates the neurodegeneration-induced by rotenone in the brain of mice. The anti-parkinsonian effect of PIRF could be attributed to their bioactive constituents of iridoids.

摘要

帕金森病是一种与年龄相关的神经退行性疾病,影响运动协调,导致多巴胺能神经元丧失。许多药物用于治疗帕金森病,但仅对症治疗,对该病的进展影响有限。因此,人们研究了从植物中提取的生物活性化合物,以研究其改善帕金森病患者神经元损伤和细胞死亡的能力。在这项研究中,从 Pentas lanceolata(PIRF)叶中分离出富含裂环烯醚萜的部分(PIRF),研究其植物成分。分离出 7 个裂环烯醚萜(1-7)和 1 个黄酮醇二糖苷(8),并通过 H 和 C 核磁共振和 ESI-MS 谱数据确定其化学结构。化合物 1(6β,7β-环氧-8-表- splendoside)和 5(gaertneroside)首次从 Pentas 属中分离出来,化合物 8(山奈酚-3-O-罗宾糖苷)也是首次从 Pentas 属中分离出来。本研究旨在使用鱼藤酮诱导的帕金森病小鼠模型研究 PIRF 的可能抗帕金森作用。治疗后,通过吊线、楼梯和木步行试验对小鼠的运动协调进行了行为测试。还评估了不同组别的脑纹状体的生化和组织病理学检查。结果表明,鱼藤酮处理的小鼠运动功能较差,表现为多巴胺和 Ach 水平下降,促炎细胞因子 IL-1B、TNF-α 和 Mcp-1 显著增加,氧化生物标志物减少,抗氧化介质减少。组织病理学检查显示纹状体紊乱、神经细胞变性、轻微空泡化、神经元皱缩伴固缩核和凋亡细胞。PIRF 治疗可改善鱼藤酮诱导的小鼠脑内神经退行性变。PIRF 的抗帕金森作用可能与其裂环烯醚萜的生物活性成分有关。

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