Wang Wenfei, Wang Yichun, Guo Qiuting, Li Huiting, Wang Zhaoqiang, Li Jia, Li Taotao, Tang Tiantian, Wang Yujiao, Jia Yanzhuo, Wang Yao, Zou Junbo, Shi Yajun, Guo Dongyan, Yang Ming, Zhang Xiaofei, Sun Jing
Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China.
School of Pharmaceutical Sciences, College of Pharmacy, Kyushu University, Fukuoka, Japan.
Front Nutr. 2022 Jul 28;9:927434. doi: 10.3389/fnut.2022.927434. eCollection 2022.
Valerian volatile oil can be used in the treatment of insomnia; however, the active components and mechanisms of action are currently unclear. Therefore, we used transcriptome sequencing and weight coefficient network pharmacology to predict the effective components and mechanism of action of valerian volatile oil in an insomnia model induced by intraperitoneal injection of para-Chlorophenylalanine (PCPA) in SD rats. Valerian essential oil was given orally for treatment and the contents of 5-hydroxytryptamine receptor 1 A (5-HT1AR), γ-aminobutyric acid (GABA), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) in the hippocampus of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA), western blot, Polymerase Chain Reaction (PCR), and immunohistochemistry. The results showed that after treatment with valerian essential oil, insomnia rats showed significantly prolonged sleep duration and alleviated insomnia-induced tension and anxiety. Regarding the mechanism of action, we believe that caryophyllene in valerian essential oil upregulates the 5-HT1AR receptor to improve the activity or affinity of the central transmitter 5-HT, increase the release of 5-HT, couple 5-HT with a G protein coupled receptor, convert adenosine triphosphate (ATP) into cAMP (catalyzed by ADCY5), and then directly regulate the downstream pathway. Following pathway activation, we propose that the core gene protein kinase PKA activates the serotonergic synapse signal pathway to increase the expression of 5-HT and GABA, thus improving insomnia symptoms and alleviating anxiety. This study provides a theoretical basis for the application of valerian volatile oil in health food.
缬草挥发油可用于治疗失眠；然而，其活性成分及作用机制目前尚不清楚。因此，我们采用转录组测序和加权系数网络药理学方法，预测缬草挥发油对腹腔注射对氯苯丙氨酸（PCPA）诱导的SD大鼠失眠模型的有效成分及作用机制。给予缬草精油口服进行治疗，采用酶联免疫吸附测定（ELISA）、蛋白质免疫印迹法、聚合酶链反应（PCR）和免疫组织化学法检测各组大鼠海马中5-羟色胺受体1A（5-HT1AR）、γ-氨基丁酸（GABA）、环磷酸腺苷（cAMP）和蛋白激酶A（PKA）的含量。结果表明，缬草精油治疗后，失眠大鼠的睡眠时间显著延长，失眠所致的紧张和焦虑得到缓解。关于作用机制，我们认为缬草精油中的石竹烯上调5-HT1AR受体，以提高中枢递质5-HT的活性或亲和力，增加5-HT的释放，使5-HT与G蛋白偶联受体结合，将三磷酸腺苷（ATP）转化为cAMP（由ADCY5催化），进而直接调节下游通路。在通路激活后，我们提出核心基因蛋白激酶PKA激活血清素能突触信号通路，以增加5-HT和GABA的表达，从而改善失眠症状并缓解焦虑。本研究为缬草挥发油在保健食品中的应用提供了理论依据。
