Isoliquiritigenin Alleviates Semen Strychni-Induced Neurotoxicity by Restoring the Metabolic Pathway of Neurotransmitters in Rats.
Isoliquiritigenin Alleviates Semen Strychni-Induced Neurotoxicity by Restoring the Metabolic Pathway of Neurotransmitters in Rats.
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DOI：
10.3389/fphar.2021.762290
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发表时间：
2021
影响因子：
5.6
通讯作者：
Fang P
中科院分区：
文献类型：
--
作者：
Wang L;Zhang M;Wen J;Xiang Y;Duan X;Yu C;Yan M;Zhang B;Fang P
马钱子的急性神经毒性可导致癫痫猝死。马钱子急性中毒的解毒方法和解毒机理尚不清楚。本实验旨在探讨马钱子神经毒性的机制及异甘草素的缓解作用。给大鼠腹腔注射马钱子提取物(125 mg/kg)，然后口服异甘草素(50 mg/kg)，连续7天。FJ-B染色评价海马神经元损伤程度。用LC-MS/MS法检测大鼠海马区、小脑、纹状体、前额叶、下丘脑、血清和血浆中单胺类、氨基酸类和胆碱类神经递质的浓度以及多巴胺(DA)和5-羟色胺(5-羟色胺)代谢途径；用酶联免疫吸附试验(ELISA法)检测神经递质代谢酶[儿茶酚-O-甲基转移酶(COMT)和单胺氧化酶(MAO)]和神经递质受体[谷氨酸N-甲基-D-天冬氨酸受体(NMDARs)和γ-氨基丁酸A型受体(GABRs)]的表达。结果表明，马钱子可引起大鼠海马神经元变性。同时，马钱子抑制NMDAR1、NMDAR2a、NMDAR2B、GABRa1、GABRb2基因的表达，降低MAO水平，从而阻断DA和5-羟色胺代谢途径。然而，异甘草素逆转了这些作用。综上所述，异甘草素具有减轻马钱子神经毒性的作用，这可能是通过恢复神经递质代谢途径，最可能是通过激活NMDA受体实现的。
Acute neurotoxicity of Semen Strychni can result in sudden death in epilepsy. The detoxification method and mechanism of Semen Strychni acute poisoning have not been clarified. This experiment focused on the mechanism of Semen Strychni neurotoxicity and the alleviation effects of isoliquiritigenin. The rats were intraperitoneally injected with Semen Strychni extract (125 mg/kg), followed by oral administration of isoliquiritigenin (50 mg/kg) for 7 days. FJ-B staining was used to evaluate the degree of injury on hippocampus neurons. The concentration of monoamines, amino acids, and choline neurotransmitters, the Dopamine (DA) and 5-hydroxytryptamine (5-HT) metabolic pathway in the hippocampus, cerebellum, striatum, prefrontal cortex, hypothalamus, serum, and plasma were detected by LC-MS/MS. The expression of neurotransmitter metabolic enzymes [catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO)] and neurotransmitter receptors [glutamate N-methyl-D-aspartic acid receptors (NMDARs) and gamma-aminobutyric acid type A receptor (GABRs)] were, respectively determined using ELISA and qRT-PCR. The results indicated that Semen Strychni induced neuronal degeneration in the hippocampal CA1 region. Meanwhile, Semen Strychni inhibited the mRNA expression of NMDAR1, NMDAR2A, NMDAR2B, GABRa1, GABRb2 and reduced the level of MAO, which disrupted the DA and 5-HT metabolic pathway. However, isoliquiritigenin reversed these effects. In summary, isoliquiritigenin showed alleviation effects on Semen Strychni-induced neurotoxicity, which could be attributed to restoring neurotransmitters metabolic pathway, most likely through the activation of NMDA receptors.
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DOI：
10.1016/j.jchromb.2015.11.012
发表时间：
2016-01-01
影响因子：
3
作者：
Lin, Aihua;Su, Xiaochun;Liu, Yiming
通讯作者：
Liu, Yiming
影响因子：
25
作者：
Graves, Steven M.;Xie, Zhong;Surmeier, D. James
通讯作者：
Surmeier, D. James
影响因子：
5
作者：
Jang, Eun Young;Choe, Eun Sang;Yang, Chae Ha
通讯作者：
Yang, Chae Ha
影响因子：
6.1
作者：
Gao, Yun;Lv, Xiaohong;Ci, Xinxin
通讯作者：
Ci, Xinxin
影响因子：
3.5
作者：
Koziol, Leonard F.;Budding, Deborah;Andreasen, Nancy;D'Arrigo, Stefano;Bulgheroni, Sara;Imamizu, Hiroshi;Ito, Masao;Manto, Mario;Marvel, Cherie;Parker, Krystal;Pezzulo, Giovanni;Ramnani, Narender;Riva, Daria;Schmahmann, Jeremy;Vandervert, Larry;Yamazaki, Tadashi
通讯作者：
Yamazaki, Tadashi