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γ-氨基丁酸能系统参与刺槐素7-O-葡萄糖苷对啮齿动物的神经保护和镇静作用。

Involvement of the GABAergic system in the neuroprotective and sedative effects of acacetin 7-O-glucoside in rodents.

作者信息

Gálvez Javier, Estrada-Reyes Rosa, Benítez-King Gloria, Araujo Gabriela, Orozco Sandra, Fernández-Mas Rodrigo, Almazán Salvador, Calixto Eduardo

机构信息

Department of Neurobiology, National Institute of Psichiatry, D.F., México.

Laboratory of Phytopharmacology, National Institute of Psichiatry, D.F., México.

出版信息

Restor Neurol Neurosci. 2015;33(5):683-700. doi: 10.3233/RNN-140486.

DOI:10.3233/RNN-140486
PMID:26410208
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4923766/
Abstract

PURPOSE

Characterization of sedative, possible anticonvulsant, and protective effects of Acacetin-7-O-glucoside (7-ACAG).

METHODS

7-ACAG was separated and its purity was analyzed. Its sedative and anti-seizure effects (1, 10, 20, and 40 mg/kg) were evaluated in male mice. Synaptic responses were acquired from area CA1 of hippocampal slices obtained from male Wistar rats. Rats were subjected to stereotaxic surgeries to allow Electroencephalographic (EEG) recordings. Functional recovery was evaluated by measuring the time rats spent in completing the motor task. Then the rats were subjected to right hemiplegia and administered 7-ACAG (40 mg/kg) 1 h or 24 h after surgery. Brains of each group of rats were prepared for histological analysis.

RESULTS

Effective sedative doses of 7-ACAG comprised those between 20 and 40 mg/kg. Latency and duration of the epileptiform crisis were delayed by this flavonoid. 7-ACAG decreased the synaptic response in vitro, similar to Gamma-aminobutyric acid (GABA) effects. The flavonoid facilitated functional recovery. This data was associated with preserved cytoarchitecture in brain cortex and hippocampus.

CONCLUSIONS

7-ACAG possesses anticonvulsive and sedative effects. Results suggest that GABAergic activity and neuroprotection are involved in the mechanism of action of 7-ACAG and support this compound's being a potential drug for treatment of anxiety or post-operative conditions caused by neurosurgeries.

摘要

目的

表征刺槐素 - 7 - O - 葡萄糖苷（7 - ACAG）的镇静、可能的抗惊厥和保护作用。

方法

分离7 - ACAG并分析其纯度。在雄性小鼠中评估其镇静和抗惊厥作用（1、10、20和40 mg/kg）。从雄性Wistar大鼠获得的海马切片CA1区获取突触反应。对大鼠进行立体定向手术以进行脑电图（EEG）记录。通过测量大鼠完成运动任务所花费的时间来评估功能恢复情况。然后使大鼠发生右侧偏瘫，并在手术后1小时或24小时给予7 - ACAG（40 mg/kg）。对每组大鼠的大脑进行组织学分析。

结果

7 - ACAG的有效镇静剂量为20至40 mg/kg。这种黄酮类化合物可延迟癫痫样发作的潜伏期和持续时间。7 - ACAG在体外降低了突触反应，类似于γ-氨基丁酸（GABA）的作用。该黄酮类化合物促进了功能恢复。这些数据与大脑皮层和海马中细胞结构的保留有关。

结论

7 - ACAG具有抗惊厥和镇静作用。结果表明，GABA能活性和神经保护作用参与了7 - ACAG的作用机制，并支持该化合物作为治疗焦虑或神经外科手术引起的术后状况的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/b5ca35573746/rnn-33-5-rnn140486-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/a3ab46b7c96f/rnn-33-5-rnn140486-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/da3b5f10564c/rnn-33-5-rnn140486-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/9e79f1de5716/rnn-33-5-rnn140486-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/1ca62f7616e9/rnn-33-5-rnn140486-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/7a7ac51c2120/rnn-33-5-rnn140486-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/2ba6f0808505/rnn-33-5-rnn140486-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/67216809a802/rnn-33-5-rnn140486-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/b5ca35573746/rnn-33-5-rnn140486-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/a3ab46b7c96f/rnn-33-5-rnn140486-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/da3b5f10564c/rnn-33-5-rnn140486-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/9e79f1de5716/rnn-33-5-rnn140486-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/1ca62f7616e9/rnn-33-5-rnn140486-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/7a7ac51c2120/rnn-33-5-rnn140486-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/2ba6f0808505/rnn-33-5-rnn140486-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/67216809a802/rnn-33-5-rnn140486-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363b/4923766/b5ca35573746/rnn-33-5-rnn140486-g008.jpg

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