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血清素及其受体在姜黄素对抗戊四氮诱导的癫痫发作中的作用。

The role of serotonin and its receptors on the anticonvulsant effect of curcumin in pentylenetetrazol-induced seizures.

机构信息

Student Research Committee, Sabzevar University of Medical Sciences, Sabzevar, Iran; Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.

Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran.

出版信息

Life Sci. 2018 Oct 15;211:252-260. doi: 10.1016/j.lfs.2018.09.007. Epub 2018 Sep 19.

DOI:10.1016/j.lfs.2018.09.007
PMID:30243647
Abstract

AIM

Curcumin, derived from turmeric, has been demonstrated to be effective in controlling seizures, although the exact mechanism is yet unknown. In this study, the role of serotonin and its receptors in the anticonvulsant effect of curcumin was evaluated in mice.

MAIN METHODS

Total 110 mice were randomly divided into 11 groups (n = 10). In the first to the fourth groups, the role of curcumin (150 mg/kg, i.p) and serotonin (PCPA (100 mg/kg); was used to deplete the brain serotonin levels) was investigated. The fifth group first received NAD-299 (4 mg/kg, sc), RS-102221 (5 mg/kg, i.p), SDZ205-557 Hydrochloride (1 mg/kg, i.p), and SB 26997 (10 mg/kg, i.p), then curcumin. The sixth group received NAD-299, curcumin. The animals in the seventh to ninth groups received 5-HT2C, 5-HT4, and 5-HT7 antagonists, respectively, with curcumin. The tenth group received HTR2C antagonist and the eleventh group received HTR4 antagonist. In all animals 25 min after curcumin PTZ (80 mg/kg; i.p) was injected.

KEY FINDINGS

PCPA not only inhibited the anticonvulsant action of curcumin, but also reversed some of its anticonvulsant effect. The 5-HT1A, 5-HT2C and 5-HT4 antagonists diminished but 5-HT7 antagonist strengthened the anticonvulsant effect of curcumin. Evaluation of gene expression using real-time PCR confirmed that only 5-HT7 gene expression was reduced after curcumin injection.

SIGNIFICANCE

According to these results, it may be suggested that curcumin exerts anticonvulsive effects by increasing the serotonin levels in the brain that influence receptors, including 5-HT1A, 5-HT2C, and 5-HT4 and likely through the reduction of 5-HT7 gene expression.

摘要

目的

姜黄素源自姜黄,已被证实可有效控制癫痫发作,尽管其确切机制尚不清楚。在这项研究中,评估了 5-羟色胺及其受体在姜黄素抗惊厥作用中的作用。

主要方法

将 110 只小鼠随机分为 11 组(n=10)。在第一至第四组中,研究了姜黄素(150mg/kg,腹腔注射)和 5-羟色胺(PCPA(100mg/kg);用于耗尽大脑 5-羟色胺水平)的作用。第五组首先接受 NAD-299(4mg/kg,皮下注射)、RS-102221(5mg/kg,腹腔注射)、SDZ205-557 盐酸盐(1mg/kg,腹腔注射)和 SB 26997(10mg/kg,腹腔注射),然后给予姜黄素。第六组接受 NAD-299 和姜黄素。第七至第九组的动物分别给予 5-HT2C、5-HT4 和 5-HT7 拮抗剂和姜黄素。第十组接受 HTR2C 拮抗剂,第十一组接受 HTR4 拮抗剂。所有动物在姜黄素(80mg/kg;腹腔注射)后 25 分钟注射 PTZ。

主要发现

PCPA 不仅抑制了姜黄素的抗惊厥作用,而且还逆转了其部分抗惊厥作用。5-HT1A、5-HT2C 和 5-HT4 拮抗剂减弱,但 5-HT7 拮抗剂增强了姜黄素的抗惊厥作用。使用实时 PCR 评估基因表达证实,只有在姜黄素注射后,5-HT7 基因表达才会减少。

意义

根据这些结果,可以认为姜黄素通过增加大脑中的 5-羟色胺水平发挥抗惊厥作用,这些 5-羟色胺水平影响包括 5-HT1A、5-HT2C 和 5-HT4 在内的受体,并且可能通过降低 5-HT7 基因表达来实现。

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