Mu Keman, Zhang Jian, Feng Xinqian, Zhang Di, Li Kangning, Li Rui, Yang Peng, Mao Shengjun
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
J Pharm Pharmacol. 2023 Jan 31;75(1):57-65. doi: 10.1093/jpp/rgac077.
Boropinol-B is a phenylpropanoid compound originally isolated from Boronia pinnata Sm. (Rutaceae). This study aimed to evaluate the sedative-hypnotic effects of Boropinol-B and explore the underlying mechanisms.
Pentobarbital sodium-induced sleep mouse model and caffeine-induced insomnia mouse model were used to investigate the sedative effects of Boropinol-B. Pharmacokinetics profiles of Boropinol-B in rats were evaluated by high-performance liquid chromatography. The effects of Boropinol-B on the γ-aminobutyric acid (GABA)ergic system were investigated using ELISA assay and patch-clamp technique. Immunohistochemistry and immunofluorescence were carried out to assess the effects of Boropinol-B on sleep-related brain nucleus.
Boropinol-B showed significant sedative effects, including reduced sleep latency, increased sleep duration in pentobarbital sodium-treated mice and decreased locomotor activity in insomnia mice. Pharmacokinetics studies demonstrated that Boropinol-B had a rapid onset of action, a short half-life and no accumulation. It increased the GABA level in mice's brain, and promoted chloride ions influx mediated by the γ-aminobutyric acid type A (GABAA) receptors in neurons. Also, it increased the c-Fos positive ratio of GABAergic neurons in ventrolateral preoptic nucleus and decreased c-Fos expression in tuberomammillary nucleus.
Boropinol-B showed significant sedative-hypnotic effects in mice by activating the GABAA receptors and stimulating the sleep-related brain nucleus.
硼硼酚-B是一种最初从羽叶硼砂（芸香科）中分离出的苯丙素类化合物。本研究旨在评估硼硼酚-B的镇静催眠作用，并探索其潜在机制。
采用戊巴比妥钠诱导的睡眠小鼠模型和咖啡因诱导的失眠小鼠模型来研究硼硼酚-B的镇静作用。通过高效液相色谱法评估硼硼酚-B在大鼠体内的药代动力学特征。使用酶联免疫吸附测定法（ELISA）和膜片钳技术研究硼硼酚-B对γ-氨基丁酸（GABA）能系统的影响。进行免疫组织化学和免疫荧光实验以评估硼硼酚-B对与睡眠相关脑核的影响。
硼硼酚-B显示出显著的镇静作用，包括缩短戊巴比妥钠处理小鼠的睡眠潜伏期、延长睡眠时间以及减少失眠小鼠的自发活动。药代动力学研究表明，硼硼酚-B起效迅速、半衰期短且无蓄积。它增加了小鼠大脑中的GABA水平，并促进了神经元中由A型γ-氨基丁酸（GABAA）受体介导的氯离子内流。此外，它增加了腹外侧视前核中GABA能神经元的c-Fos阳性率，并降低了结节乳头核中的c-Fos表达。
硼硼酚-B通过激活GABAA受体和刺激与睡眠相关的脑核，在小鼠中显示出显著的镇静催眠作用。
