Ligustilide prevents cognitive impairment and attenuates neurotoxicity in D-galactose induced aging mice brain
Ligustilide prevents cognitive impairment and attenuates neurotoxicity in D-galactose induced aging mice brain
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DOI：
10.1016/j.brainres.2014.10.012
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发表时间：
2015-01-21
期刊：
影响因子：
2.9
通讯作者：
Zhu, Li
中科院分区：
文献类型：
--
作者：
Li, Jie-Jia;Zhu, Qing;Zhu, Li
阿替利特（LIG）是中药当归的主要活性成分，具有神经保护等多种药理作用。先前的研究已经证明LIG对与脑损伤或神经退行性疾病相关的认知缺陷具有有益作用。本研究探讨了LIG对D-半乳糖（D-gal）致衰老小鼠认知功能障碍和脑神经毒性的保护作用。采用皮下注射（S.C.）注射D-gal，每日一次，持续8周，同时口服LIG（80 mg/kg）。采用Morris水迷宫（MWM）测试大鼠的空间学习记忆能力。测定脑组织Na+-K+-ATP酶活性和脂质过氧化产物丙二醛（MDA）含量。免疫组化法检测脑组织中胶质细胞酸性蛋白（GFAP）、生长相关蛋白GAP-43和半胱天冬酶-3的表达。MWM测试表明，LIG给药显著改善了D-gal处理的小鼠的行为表现。这可能与LIG降低D-半乳糖致衰老小鼠脑内MDA含量，提高Na ~+-K ~+-ATP酶活性有关。此外，LIG显着提高GAP-43的表达，并降低切割的caspase-3和GFAP水平在D-半乳糖治疗的小鼠的脑中。这些结果表明，LIG改善了D-半乳糖诱导的认知功能障碍和脑毒性，这表明LIG可能被开发为治疗老年相关疾病的新药。(C)2014爱思唯尔有限公司版权所有。
Ligustilide (LIG) is a principal active ingredient of traditional Chinese medicine, Radix Angelica sinensis, which has versatile pharmacological activities including neuroprotection. Previous studies have demonstrated that LIG has beneficial effects on cognition deficits associated with cerebral damage or neurodegenerative disorders. In present study, we investigated the neuroprotective effect of LIG on cognitive impairment and neurotoxicity in the brain of aging mouse induced by D-galactose (D-gal). The aging model mice were induced by subcutaneous (S.C.) injection of D-gal once daily for 8 weeks and LIG (80 mg/kg) was simultaneously administered orally. The Morris water maze (MWM) test was used to assess the spatial learning and memory abilities. The activity of Na+-K+-ATPase and the content of lipid peroxidation product malondialdehyde (MDA) in brain were examined. The levels of glial fibrillary acidic protein (GFAP), growth-associated protein GAP-43, and cleaved caspase-3 in brain were also determined by immunohistochemistry. The MWM test showed that LIG administration markedly improved behavioral performance of D-gal treated mice. This action could be partly explained by the results that LIG reduced the level of MDA as well as increased the activity of Na+-K+-ATPase in the brain of D-gal induced aging mice. Moreover, LIG significantly raised the expression of GAP-43 and reduced cleaved caspase-3 and GFAP levels in the brain of D-gal treated mice. These results demonstrated that LIG improves D-gal-induced cognitive dysfunction and brain toxicity, which suggests that LIG may be developed as a new medicine for the treatment of aged-related conditions. (C) 2014 Elsevier B.V. All rights reserved.