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水提物对三甲基锡诱导的癫痫发作和海马神经退行性变的神经保护作用。

Neuroprotective Effect of ' Water Extract on Trimethyltin-Induced Seizures and Hippocampal Neurodegeneration.

机构信息

Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju 58245, Korea.

College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Korea.

出版信息

Int J Mol Sci. 2021 Jan 12;22(2):679. doi: 10.3390/ijms22020679.

DOI:10.3390/ijms22020679
PMID:33445535
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7827571/
Abstract

This study aimed to investigate whether the (PB)' water extract (PBWE) ameliorates trimethyltin (TMT)-induced seizures and hippocampal neurodegeneration. To investigate the potential neuroprotective effect of the PBWE in vitro, a lactate dehydrogenase (LDH) assay was conducted in TMT-treated primary cultures of mouse hippocampal neurons. In TMT-treated adult C57BL/6 mice, behavioral and histopathological changes were evaluated by seizure scoring and Fluoro-Jade C staining, respectively. In our in vitro assay, we observed that pretreating mice hippocampal neuron cultures with the PBWE reduced TMT-induced cytotoxicity, as indicated by the decreased LDH release. Furthermore, pretreatment with the PBWE alleviated seizures and hippocampal neurodegeneration in TMT-treated mice. The antioxidant activity of the PBWE increased in a dose-dependent manner; moreover, pretreatment with the PBWE mitigated the TMT-induced Nrf2 stimulation. In addition, six major compounds, including adenine, hypoxanthine, uridine, adenosine, inosine, and benzoic acid, were isolated from the PBWE, and among them, inosine and benzoic acid have been confirmed to have an essential antioxidative activity. In conclusion, the PBWE ameliorated TMT-induced toxicity in hippocampal neurons in both in vitro and in vivo assays, through a potential antioxidative effect. Our findings suggest that the PBWE may have pharmacotherapeutic potential in neurodegenerative diseases such as seizures or epilepsy.

摘要

本研究旨在探讨 (PB) 的水提取物 (PBWE) 是否能改善三甲基锡 (TMT) 诱导的癫痫发作和海马神经退行性变。为了研究 PBWE 在体外的潜在神经保护作用，我们在 TMT 处理的小鼠海马神经元原代培养物中进行了乳酸脱氢酶 (LDH) 测定。在 TMT 处理的成年 C57BL/6 小鼠中，通过癫痫评分和 Fluoro-Jade C 染色分别评估行为和组织病理学变化。在我们的体外实验中，我们观察到 PBWE 预处理可减少 TMT 诱导的小鼠海马神经元培养物的细胞毒性，这表现在 LDH 释放减少。此外，PBWE 预处理可减轻 TMT 处理小鼠的癫痫发作和海马神经退行性变。PBWE 的抗氧化活性呈剂量依赖性增加；此外，PBWE 预处理可减轻 TMT 诱导的 Nrf2 刺激。此外，从 PBWE 中分离出包括腺嘌呤、次黄嘌呤、尿嘧啶、腺苷、肌苷和苯甲酸在内的六种主要化合物，其中肌苷和苯甲酸已被证实具有重要的抗氧化活性。总之，PBWE 通过潜在的抗氧化作用，改善了体外和体内实验中 TMT 诱导的海马神经元毒性。我们的研究结果表明，PBWE 可能在癫痫或癫痫等神经退行性疾病的治疗中具有潜在的治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c9a/7827571/432f117181b5/ijms-22-00679-g006.jpg
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