Abstract：
BACKGROUND: Sclareol (SCL), a labdane diterpene compound found in Salvia sclarea L., exhibited therapeutic effects. This study investigated the potential interaction between SCL and diazepam (DZP) in modulating sedation in the thiopental sodium-induced sleeping animal model, supported by in-silico molecular docking analysis.
METHODS: The control, sclareol (5, 10 and 20 mg/kg), and the reference drugs [diazepam: 3 mg/kg and Caffeine (CAF): 10 mg/kg] were used in male albino mice. Then, sodium thiopental (40 mg/kg, i.p.) was administrated to induce sleep. The latent period, percentage of sleep incidence and modulation of latency were measured. Further, homology modeling of human γ-aminobutyric acid (GABA) was conducted examine the binding mode of GABA interaction with SCL, DZP, and CAF compounds RESULTS: SCL (low dose) slightly increased the sleep latency, while the higher dose significantly prolonged sleep latency. DZP, a GABAA receptor agonist, exhibited strong sleep-inducing properties, reducing sleep latency, and increasing sleeping time. Caffeine (CAF) administration prolonged sleep latency and reduced sleeping time, consistent with its stimulant effects. The combination treatments involving SCL, DZP, and CAF showed mixed effects on sleep parameters. The molecular docking revealed good binding affinities of SCL, DZP, and CAF for GABAA receptor subunits A2 and A5.
CONCLUSIONS: Our findings highlighted the complex interplay between SCL, DZP, and CAF in regulating sleep behaviors and provided insights into potential combination therapies for sleep disorders.
METHODS: The control, sclareol (5, 10 and 20 mg/kg), and the reference drugs [diazepam: 3 mg/kg and Caffeine (CAF): 10 mg/kg] were used in male albino mice. Then, sodium thiopental (40 mg/kg, i.p.) was administrated to induce sleep. The latent period, percentage of sleep incidence and modulation of latency were measured. Further, homology modeling of human γ-aminobutyric acid (GABA) was conducted examine the binding mode of GABA interaction with SCL, DZP, and CAF compounds RESULTS: SCL (low dose) slightly increased the sleep latency, while the higher dose significantly prolonged sleep latency. DZP, a GABAA receptor agonist, exhibited strong sleep-inducing properties, reducing sleep latency, and increasing sleeping time. Caffeine (CAF) administration prolonged sleep latency and reduced sleeping time, consistent with its stimulant effects. The combination treatments involving SCL, DZP, and CAF showed mixed effects on sleep parameters. The molecular docking revealed good binding affinities of SCL, DZP, and CAF for GABAA receptor subunits A2 and A5.
CONCLUSIONS: Our findings highlighted the complex interplay between SCL, DZP, and CAF in regulating sleep behaviors and provided insights into potential combination therapies for sleep disorders.
摘要：
背景：香瑞尔（SCL），在丹参中发现的拉伯丹二萜化合物，表现出治疗效果。这项研究调查了SCL和地西泮（DZP）在调节硫喷妥钠诱导的睡眠动物模型中的镇静作用，由计算机分子对接分析支持。
方法：对照，香雷醇（5、10和20mg/kg），在雄性白化病小鼠中使用参考药物[地西泮：3mg/kg和咖啡因（CAF）：10mg/kg]。然后，硫喷妥钠（40毫克/千克，i.p.)给药诱导睡眠。潜伏期，测量睡眠发生率的百分比和潜伏期的调节。Further,进行人γ-氨基丁酸（GABA）的同源性建模，检查GABA与SCL相互作用的结合模式，DZP,和CAF化合物结果：SCL（低剂量）略微增加了睡眠潜伏期，而较高的剂量可显着延长睡眠潜伏期。DZP,一种GABAA受体激动剂,表现出强烈的睡眠诱导特性，减少睡眠延迟，增加睡眠时间。咖啡因（CAF）管理延长睡眠潜伏期和减少睡眠时间，与其兴奋剂效果一致。涉及SCL的联合治疗，DZP,和CAF对睡眠参数显示混合影响。分子对接显示SCL良好的结合亲和力，DZP,和CAF的GABAA受体亚基A2和A5。
结论：我们的发现强调了SCL之间复杂的相互作用，DZP,和CAF在调节睡眠行为方面，并提供了对睡眠障碍的潜在组合疗法的见解。
方法：对照，香雷醇（5、10和20mg/kg），在雄性白化病小鼠中使用参考药物[地西泮：3mg/kg和咖啡因（CAF）：10mg/kg]。然后，硫喷妥钠（40毫克/千克，i.p.)给药诱导睡眠。潜伏期，测量睡眠发生率的百分比和潜伏期的调节。Further,进行人γ-氨基丁酸（GABA）的同源性建模，检查GABA与SCL相互作用的结合模式，DZP,和CAF化合物结果：SCL（低剂量）略微增加了睡眠潜伏期，而较高的剂量可显着延长睡眠潜伏期。DZP,一种GABAA受体激动剂,表现出强烈的睡眠诱导特性，减少睡眠延迟，增加睡眠时间。咖啡因（CAF）管理延长睡眠潜伏期和减少睡眠时间，与其兴奋剂效果一致。涉及SCL的联合治疗，DZP,和CAF对睡眠参数显示混合影响。分子对接显示SCL良好的结合亲和力，DZP,和CAF的GABAA受体亚基A2和A5。
结论：我们的发现强调了SCL之间复杂的相互作用，DZP,和CAF在调节睡眠行为方面，并提供了对睡眠障碍的潜在组合疗法的见解。
