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香茅油通过调节 MAPK 通路和血清素系统逆转 1-(3-氯苯基)哌嗪诱导的小鼠焦虑。

Cananga odorata essential oil reverses the anxiety induced by 1-(3-chlorophenyl) piperazine through regulating the MAPK pathway and serotonin system in mice.

机构信息

School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, China.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, China.

出版信息

J Ethnopharmacol. 2018 Jun 12;219:23-30. doi: 10.1016/j.jep.2018.03.013. Epub 2018 Mar 12.

DOI:10.1016/j.jep.2018.03.013
PMID:29545208
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Cananga odorata essential oil, known as ylang-ylang essential oil (YYO), was commonly used in the aromatherapy for relaxation and mood adjusting use. In our previous study, YYO played anxiolytic effects on the mice in several behavioral tests that based on the instinctive responses to novel environments.

AIM OF THE STUDY

To investigate the effects and mechanisms of YYO reversing the anxiety induced by 5-HT2C receptor agonist 1-(3-chlorophenyl) piperazine (m-CPP).

MATERIALS AND METHODS

m-CPP was administrated to the male ICR mice to develop an anxiety model. The anxiolytic effect of YYO (0.1%, 1% and 10%, v/v) was evaluated in the elevated plus maze (EPM) test after odor exposure. Western blot was used to detect the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) and the expression of c-Fos in the prefrontal cortex (PFC) and hippocampus after the EPM test. Serotonin and its metabolite change in the brain were detected by liquid chromatogram with an electrochemical detector. The effect of YYO on the plasma corticosterone level was evaluated using enzyme-linked immunosorbent assay (ELISA) after the odor exposure.

RESULTS

The behavior analysis showed that m-CPP (2 mg/kg and 4 mg/kg) could induce anxiety behaviors in the mice while diazepam (2 mg/kg) reversed the anxiety behavior induced by m-CPP. YYO dose-dependently increased the time and number of entries in the open arms (p < 0.05) compared to the Tween 80 group. YYO reduced the phosphorylation levels of ERK1/2 (p < 0.05) in both PFC and hippocampus. Down-regulations of phosphor-CREB (p < 0.05) and c-Fos (p < 0.05) were only observed in the hippocampus. YYO also affected the brain serotonin metabolism and reduced the blood plasma corticosterone level of the m-CPP treated mice.

CONCLUSION

YYO odor exposure could reverse the anxiety behaviors generated by m-CPP. The anxiolytic effect of YYO was associated with the ERK1/2/CREB pathway in the hippocampus and relevant to the serotonin system.

摘要

民族药理学相关性

依兰依兰精油(简称 YYO)作为一种常见的香薰油,常用于放松和调节情绪。在我们之前的研究中,YYO 在几种基于对新环境本能反应的行为测试中对小鼠表现出抗焦虑作用。

研究目的

研究 YYO 对 5-HT2C 受体激动剂 1-(3-氯苯基)哌嗪(m-CPP)诱导焦虑的作用及其机制。

材料和方法

用 m-CPP 对雄性 ICR 小鼠进行处理以建立焦虑模型。在气味暴露后,通过高架十字迷宫(EPM)测试评估 YYO(0.1%、1%和 10%,v/v)的抗焦虑作用。通过 Western blot 检测 EPM 测试后前额叶皮层(PFC)和海马中海马磷酸化细胞外信号调节激酶 1/2(ERK1/2)和 cAMP 反应元件结合蛋白(CREB)的磷酸化水平和 c-Fos 的表达。采用液相色谱-电化学检测法检测脑内 5-羟色胺及其代谢产物的变化。通过酶联免疫吸附试验(ELISA)检测 YYO 对气味暴露后血浆皮质酮水平的影响。

结果

行为分析表明,m-CPP(2mg/kg 和 4mg/kg)可诱导小鼠出现焦虑行为,而地西泮(2mg/kg)可逆转 m-CPP 诱导的焦虑行为。与吐温 80 组相比,YYO 剂量依赖性地增加了开放臂的时间和进入次数(p<0.05)。YYO 降低了 PFC 和海马中海马磷酸化 ERK1/2 的水平(p<0.05)。仅在海马中观察到磷酸化 CREB(p<0.05)和 c-Fos(p<0.05)的下调。YYO 还影响脑内 5-羟色胺代谢,降低 m-CPP 处理小鼠的血浆皮质酮水平。

结论

YYO 气味暴露可逆转 m-CPP 产生的焦虑行为。YYO 的抗焦虑作用与海马中的 ERK1/2/CREB 通路有关,并与 5-羟色胺系统有关。

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