石榴（Punica granatum L.）汁和籽提取物对百草枯诱导的帕金森病小鼠模型的神经保护作用。
Neuroprotective effects of pomegranate (Punica granatum L.) juice and seed extract in paraquat-induced mouse model of Parkinson's disease.
机构信息
Zoology Department, Faculty of Science, Fayoum University, Fayoum, Egypt.
出版信息
BMC Complement Med Ther. 2021 Apr 26;21(1):130. doi: 10.1186/s12906-021-03298-y.
BACKGROUND
Paraquat, (PQ), an herbicide that can induce Parkinsonian-like symptoms in rodents and humans. The consumption of phytochemical-rich plants can reduce the risk of chronic illnesses such as inflammation and neurodegenerative diseases. The present study aimed to investigate the protective effects of pomegranate seed extract (PSE) and juice (PJ) against PQ-induced neurotoxicity in mice.
METHODS
Mice were assigned into 4 groups; three groups received PQ (10 mg/kg, i.p.) twice a week for 3 weeks. Two of the PQ-induced groups pretreated with either PSE or PJ. Detection of phytochemicals, total phenolics, and total flavonoids in PSE and PJ was performed. Tyrosine hydroxylase (TH) level was measured in the substantia nigra (SN) by Western blotting technique. Striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were detected using high-performance liquid chromatography (HPLC). The levels of adenosine triphosphate (ATP), malondialdehyde (MDA), and the activity of the antioxidant enzymes were estimated in the striatum by colorimetric analysis. Striatal pro-inflammatory and anti-inflammatory markers using enzyme-linked immunosorbent assay (ELISA) as well as DNA fragmentation degree by qualitative DNA fragmentation assay, were evaluated. Real-time polymerase chain reaction (qPCR) assay was performed for the detection of nuclear factor kappa B (NF-кB) gene expression. Moreover, Western blotting analysis was used for the estimation of the cluster of differentiation 11b (CD11b), transforming growth factor β (TGF-β), and glial cell-derived neurotrophic factor (GDNF) levels in the striatum.
RESULTS
Pretreatment with PSE or PJ increased the levels of TH in the SN as well as DA and its metabolite in the striatum that were reduced by PQ injection. PSE and PJ preadministration improved the PQ-induced oxidative stress via a significant reduction of the MDA level and the augmentation of antioxidant enzyme activities. PSE and PJ also significantly downregulated the striatal NF-кB gene expression, reduced the PQ-enhanced apoptosis, decreased the levels of; pro-inflammatory cytokines, CD11b, and TGF-β coupled with a significant increase of; interleukin-10 (IL-10), GDNF, and ATP levels as compared with PQ-treated mice.
CONCLUSIONS
The current study indicated that PSE and PJ consumption may exhibit protective effects against PQ-induced neurotoxicity in mice.
背景
百草枯（PQ）是一种除草剂，可在啮齿动物和人类中诱导出类似帕金森病的症状。食用富含植物化学物质的植物可以降低炎症和神经退行性疾病等慢性疾病的风险。本研究旨在探讨石榴籽提取物（PSE）和石榴汁（PJ）对 PQ 诱导的小鼠神经毒性的保护作用。
方法
将小鼠分为 4 组；三组每周两次腹腔注射 PQ（10mg/kg），共 3 周。其中两组 PQ 诱导组预先用 PSE 或 PJ 处理。通过高效液相色谱法（HPLC）检测 PSE 和 PJ 中的植物化学物质、总酚和总类黄酮。通过 Western 印迹技术测量黑质（SN）中的酪氨酸羟化酶（TH）水平。使用 HPLC 检测纹状体中的多巴胺（DA）和 3,4-二羟基苯乙酸（DOPAC）。通过比色分析估计纹状体中的三磷酸腺苷（ATP）、丙二醛（MDA）和抗氧化酶的活性。通过酶联免疫吸附测定（ELISA）评估纹状体中的促炎和抗炎标志物，以及通过定性 DNA 片段化测定评估 DNA 片段化程度。通过实时聚合酶链反应（qPCR）检测核因子 kappa B（NF-кB）基因表达。此外，通过 Western 印迹分析估计纹状体中的分化群 11b（CD11b）、转化生长因子-β（TGF-β）和胶质细胞源性神经营养因子（GDNF）水平。
结果
用 PSE 或 PJ 预处理可增加 SN 中的 TH 水平以及 PQ 注射降低的纹状体中的 DA 及其代谢物。PSE 和 PJ 预处理通过显著降低 MDA 水平和增加抗氧化酶活性来改善 PQ 诱导的氧化应激。PSE 和 PJ 还显著下调了纹状体 NF-кB 基因表达，降低了 PQ 增强的细胞凋亡，降低了促炎细胞因子、CD11b 和 TGF-β的水平，同时显著增加了白细胞介素 10（IL-10）、GDNF 和 ATP 的水平，与 PQ 处理的小鼠相比。
结论
本研究表明，PSE 和 PJ 的摄入可能对 PQ 诱导的小鼠神经毒性具有保护作用。
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