• Yu Zhong, Qin Zheng, Pengyi Hu, Xiaoying Huang, Ming Yang, Guilin Ren, Jing Li, Qing Du, Shanshan Liu, Kenan Zhang, Ling Wu, Liyun Zhu, Yuanyuan Guo, Wenjing Li, Shuai Xiao, Shuyuan Shuai, and Mingxia Zhang.
• Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, State Key Lab.of Innovation Drug and Effcient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
• J Ethnopharmacol. 2021 Oct 28; 279: 113627.

Ethnopharmacological RelevanceTraditional Chinese medicine believes that depression syndrome has become one of the core pathogenesis of insomnia. The pharmacology of traditional Chinese medicine points out that Perilla frutescens has the effect of regulating Qi and relieving depression, promoting Qi circulation to relieve pain, so Perilla frutescens may have the potential therapeutic effect on insomnia. Related studies have reported the sedative and hypnotic effects of Perilla frutescens, but these studies have not yet explored the mechanism of sedative and hypnotic effects of Perilla frutescens essential oil (PFEO) through inhalation administration.Aim Of The StudyThe purpose of this study is to explore the underlying sedative and hypnotic mechanisms of PFEO through the GABAergic system pathways.Materials And MethodsEstablished the PCPA insomnia model of mice, The open field test, pentobarbital-induced falling asleep rate, latency of sleeping time, and duration of sleeping time experiments were used to evaluate the behavior of mice, the enzyme-linked immunosorbent assay was used to analyze the content of 5-HT and GABA in hypothalamus and cerebral cortex. Immunohistochemical experiment, Western blot experiment and RT-PCR experiment were used to study the mechanism of PFEO through GABAergic pathway to regulate insomnia. The main volatile constituents of PFEO were analyzed by gas chromatography-mass spectrometry (GC-MS).ResultsThe inhalation of PFEO has sedative and hypnotic effects, which reduce significantly the autonomic activity of PCPA insomnia mice, increase falling asleep rate, shorten latency of sleeping time, and prolong duration of sleeping time; the results of enzyme-linked immunosorbent assay show that PFEO increase the content of 5-HT and GABA in hypothalamus and cerebral cortex. The results showed that inhalation of PFEO increase the expression of GABAAα1 and GABAAα2 positive cells, increase the level of GABAAα1 and GABAAα2 protein and also increase the level of GABAAα1 mRNA and GABAAα2 mRNA in the hypothalamus and cerebral cortex. The highest content of PFEO is Perillaldehyde (54.37%), followed by 1,4-Cineole (7.42%), Acetaldehyde diethyl acetal (6.61%), D-Limonene (5.09%), Eucalyptol (4.94%), etc. CONCLUSION: The inhalation of PFEO has sedative and hypnotic effects, it is speculated that the mechanism of which may be the sedative and hypnotic effects through the GABAergic pathway.Copyright © 2020 Elsevier B.V. All rights reserved.

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