Sedative, hypnotic and anticonvulsant activities of the ethanol fraction from Rhizoma Pinelliae Praeparatum

Ethnopharmacological relevance

Rhizoma Pinelliae Praeparatum is the product of raw Rhizoma Pinellia processed with alkaline solution and Licorice, which had been widely used for treatment of insomnia in traditional Chinese medicine. The present study aimed to investigate the sedative, hypnotic and anticonvulsant activities of ethanol fraction from Rhizoma Pinelliae Praeparatum (EFRP) and to determine whether these effects were related to GABAergic mechanism.

Materials and methods

The sedative, hypnotic and anticonvulsant activities of EFRP were investigated with locomotion activity, pentobarbital-induced sleeping and nikethamide (NKTM)-induced convulsion tests, respectively. Additionally, the effects of flumazenil (an antagonist of GABA_A receptor) and l-malic acid (blocker of synthetic enzyme for GABA) on the hypnotic activity of EFRP were evaluated.

Results

EFRP at dose of 12 g/kg significantly inhibited the locomotion activity of mice. EFRP showed synergic effect on pentobarbital-induced sleeping by increased numbers of mice falling asleep, reduced the sleep latency and prolonged the sleeping time. l-malic acid and flumazenil inhibited the augment effects of EFRP on pentobarbital-induced sleeping. EFRP promoted a significant protection to NKTM-induced convulsion, by prolonged the death latency and decreased mortality.

Conclusion

EFRP possessed sedative, hypnotic and anticonvulsant activities and these activities may be related to the GABAergic system.     

蛇床子提取物的镇静催眠作用

目的:比较蛇床子不同提取物的镇静催眠作用。方法:蛇床子用水、乙醇、石油醚分别提取制备,观察折合生药相当剂量水提物和等剂量挥发油、醇提物、总香豆素对小鼠自主活动和对戊巴比妥钠催眠剂量小鼠入睡潜伏期和睡眠时间的影响。结果:蛇床子醇提物、总香豆素能显著减少小鼠自主活动(P<0.05),延长小鼠睡眠时间(P<0.05,P<0.001),醇提物作用更为显著;蛇床子水提物、挥发油对小鼠自主活动、睡眠潜伏期和持续睡眠时间与空白对照组比较,无统计学意义。结论:初步确定蛇床子醇提物、总香豆素具有明显的镇静催眠作用,以醇提物作用较强。     

黑水缬草挥发油对中枢神经系统药理作用的研究

目的：观察黑水缬草挥发油对中枢神经系统的作用。方法：考察黑水缬草挥发油对小鼠自主活动的影响、对阈下和催眠剂量戊巴比妥钠的睡眠协同作用、对大鼠睡眠时相的影响、对醋酸所致小鼠扭体反应的影响以及对硫代氨基脲诱发小鼠惊厥的影响。结果：黑水缬草挥发油对小鼠的自主活动具有显著的抑制作用，与戊巴比妥钠有较好的催眠协同作用，可提高小鼠的入睡率，延长小鼠睡眠时间，明显延长大鼠睡眠周期中的慢波睡眠Ⅱ期（SWS2）和快动眼睡眠期（REMS）两个时相，同时能明显减少小鼠扭体反应次数，对抗硫代氨基脲诱发的小鼠惊厥。结论：黑水缬草挥发油具有显著的镇静、镇痛和抗惊厥等中枢神经系统抑制作用，预示了良好的新药开发前景。     

赤芝孢子粉肠溶滴丸对大鼠镇静催眠作用研究

目的:研究赤芝孢子粉提取物肠溶滴丸灌胃给药后对大鼠的镇静催眠作用。方法:采用阈上和阈下剂量戊巴比妥钠、致大鼠睡眠的方法,考察不同剂量、不同给药方式下赤芝孢子粉提取物对大鼠睡眠时间及主动活动等的影响。结果:采用阈上剂量戊巴比妥钠诱导大鼠催眠作用表明,灌胃孢子粉肠溶滴丸1.5及2.5g/kg,可明显延长睡眠时间(p<0.01);采用阈下剂量戊巴比妥钠诱导大鼠催眠作用表明,灌胃孢子粉肠溶滴丸1.5及2.5g/kg,可明显延长睡眠时间(p<0.05),与皮下同剂量注射给药相比无显著性差异。结论:赤芝孢子粉提取物肠溶滴丸剂对于大鼠具有镇静催眠作用。     

Sedative and hypnotic effect of freeze-dried paeoniflorin and Sini San freeze-dried powder in pentobarbital sodium-induced mice

Objective

To investigate the sedative and hypnotic activity of paeoniflorin and freeze-dried Sini San powder on mice and provide a reliable method for determining the pharmacodynamic material basis of Sini San.

Methods

Male adult mice weighing 20–22 g were used in this study. Three experiments were carried out. Synergism with pentobarbital was used as an index for hypnotic effect. Loss of the righting reflex was used to determine the start of sleep. Sleep latency and sleeping time were recorded in each experiment.

Results

The coefficient of variation of the supra-threshold dose (55 mg/kg) was significantly lower than that of the threshold dose. The sleep latency of mice was significantly decreased, and the sleeping time of mice was significantly prolonged. The effects of paeoniflorin and Sini San on prolonging the sleeping time of mice induced by pentobarbital sodium were significantly stronger than those in the control group.

Conclusion

Paeoniflorin produces significant sedative and hypnotic effects, and there is an obvious dose-effect relationship.     

赤灵芝孢子粉水溶性提取物(肌生注射液)对小鼠的催眠镇静作用

目的：研究赤灵芝孢子粉水提物（肌生注射液）对小鼠中枢神经系统的作用。方法：以翻正反射消失出现时间作为睡眠时间,观察不同剂量和给药方式下肌生液对小鼠戊巴比妥钠和巴比妥钠睡眠时间及自主活动等的影响。结果：皮下注射肌生液可明显延长小鼠戊巴比妥钠和巴比妥钠睡眠时间,且有剂量效应关系。肌生液亦可诱导注射阈下剂量的戊巴比妥的小鼠入睡。每日注射具有镇静作用剂量的肌生液一次连续8天不产生依赖性,而安定连续给药8天后产生依赖性。肌生液可明显减少小鼠的自主活动。结论：灵芝孢子粉水提物对小鼠中枢神经系统具有镇静催眠的效果。     

养心安神药与重镇安神药对失眠大鼠睡眠时相影响的比较研究

目的：比较养心安神药和重镇安神药改善睡眠时相作用的异同。方法：在恒温、恒湿、自动光控和电磁屏蔽实验条件下,采用多导睡眠描记方法,观察养心安神药与重镇安神药对大鼠睡眠时相的影响。结果：柏子仁（Semen Platycladi）、远志（Radix Polygalae）可延长失眠大鼠睡眠时相中的SWS1期,但不缩短SWS2期和REMS期;酸枣仁(Semen Ziziphi Spinosae)延长失眠大鼠的SWS1期和SWS2期;磁石(Magnetitum)、朱砂(Cinnabari)同时延长SWS1期、SWS2期和REMS期。结论：养心安神药对REMS期无影响,而重镇安神药对REMS期有影响;与养心安神药相比,重镇安神药的磁石、朱砂对失眠大鼠的慢波睡眠延长作用更明显,可显著提高失眠大鼠的睡眠质量。     

参芪五味子颗粒协同戊巴比妥钠对小鼠睡眠及免疫器官指数的影响

目的观察参芪五味子颗粒协同戊巴比妥钠对小鼠睡眠的影响,研究参芪五味子颗粒的镇静催眠作用。方法将60只小鼠随机分为空白对照组、西药对照组(地西泮组)、中药对照组(参芪五味子片组)和参芪五味子颗粒高、中、低剂量组。西药对照组给予地西泮(3μg/g),中药对照组给予参芪五味子片(0.75 g/kg),参芪五味子颗粒高、中、低剂量组分别给予1.44 g/kg、0.72 g/kg、0.36 g/kg剂量的参芪五味子颗粒,空白对照组给予等体积蒸馏水,连续灌胃给药7天。通过观察小鼠睡眠时间、睡眠潜伏期,以及阈下剂量戊巴比妥钠诱导小鼠入睡只数,确定参芪五味子颗粒的镇静催眠作用;并检测小鼠脾脏指数和胸腺指数,考察制剂对小鼠免疫器官指数的影响。结果与空白对照组比较,参芪五味子颗粒高、中剂量能显著增加阈下剂量戊巴比妥钠诱导小鼠入睡只数(P0.01),参芪五味子颗粒高、中、低剂量均能明显延长小鼠睡眠时间(P0.05,P0.01),而参芪五味子颗粒对小鼠的脾脏指数和胸腺指数均没有显著影响。参芪五味子颗粒高、中、低剂量组协同阈下剂量戊巴比妥钠诱导小鼠入睡只数少于地西泮组(P0.05,P0.01),但参芪五味子颗粒高、中剂量组对小鼠入睡率的影响较参芪五味子片组明显增加(P0.05)。参芪五味子颗粒高、低剂量组小鼠入睡时间与地西泮组差异无统计学意义(P0.05),但较参芪五味子片组小鼠的入睡时间显著延长(P0.01)。结论参芪五味子颗粒能协同戊巴比妥钠诱导小鼠睡眠,具有良好的镇静催眠作用。     

茯苓及其化学拆分组分学习记忆及镇静催眠的性味药理学研究

目的 评价茯苓及其拆分组分的活性,并结合中医传统理论对其进行性味归属。方法 采用东莨菪碱造成小鼠记忆障碍并应用Morris水迷宫实验,观察茯苓及其组分对学习记忆的影响,同时应用抖笼法及戊巴比妥钠协同催眠实验来观察茯苓及其组分的镇静催眠作用。结果 茯苓水煎液（生药8.56 g/kg）、醋酸乙酯组分、石油醚组分、粗多糖组分及精制多糖组分均能明显缩短小鼠到达平台的潜伏期,并且降低东莨菪碱所致记忆障碍小鼠大脑乙酰胆碱酯酶（AchE）活性,醇洗物与水洗物对潜伏期的影响不明显,各个组分对于小鼠的脑指数均有不同程度的增加;生药42.8 g/kg茯苓水煎液可显著延长阈上剂量戊巴比妥钠引起小鼠睡眠时间,而对小鼠睡眠潜伏期没有影响;茯苓粗多糖能显著缩短小鼠的睡眠潜伏期,并且与精制多糖组分均能显著延长小鼠睡眠时间,醋酸乙酯组分作用次之。结论 茯苓改善学习记忆和镇静催眠作用都与其味甘入脾能健脾宁心相关,其醋酸乙酯、石油醚及多糖拆分组分可能为其甘味的物质基础。     

双夏汤不同洗脱液镇静催眠作用研究

目的：研究双夏汤不同洗脱液的镇静催眠作用。方法：通过测定小鼠自主活动和对戊巴比妥钠阈下剂量诱导睡眠的作用,观察双夏汤水煎液、水洗液、20%、70%和95%醇洗液的镇静催眠作用。结果：双夏汤水煎液、20%和95%醇洗液显著降低小鼠的站立次数,分别为78.5%,78.3%和62.5%;双夏汤水洗液和70%醇洗液能显著降低小鼠自主活动次数（P<0.01）、站立次数（P<0.01）和修饰时间（P<0.05）。双夏汤水煎液能明显缩短小鼠睡眠的潜伏期（P<0.05）,延长小鼠睡眠时间（P<0.05）,增加小鼠的入睡率。双夏汤水洗液能显著缩短小鼠睡眠潜伏期（P<0.05）,增加小鼠的入睡率。结论：双夏汤水煎液和水洗液的镇静催眠作用优于醇洗液。     

柴胡加龙骨牡蛎汤对去卵巢大鼠睡眠时相的影响

目的:探讨去卵巢大鼠脑电图的变化及中药复方柴胡加龙骨牡蛎汤对其影响。方法:以去卵巢大鼠为动物模型,采用大鼠皮层脑电图描记技术,从睡眠时相方面阐明柴胡加龙骨牡蛎汤改善更年期失眠症的药理作用。结果:去卵巢大鼠睡眠时相中的慢波睡眠深睡期(Slow wave sleep 2,SWS2)持续时间明显低于假手术组,给予柴胡加龙骨牡蛎汤7d后能明显延长自由活动去卵巢大鼠SWS2,对SWS1(Slow wave sleep1,慢波睡眠浅睡期)和REMS(rapid eyes movement sleep,快速眼球运动睡眠)没有明显的影响。结论:柴胡加龙骨牡蛎汤具有改善去卵巢大鼠睡眠的作用。     

龙胆碱镇静催眠作用及对小鼠脑内5-HT、GABA含量的影响

目的探讨龙胆碱的镇静、催眠作用,并观察其对脑内递质5-HT、GABA含量影响,初步探讨龙胆碱镇静催眠作用的机制。方法腹腔注射不同剂量的龙胆碱溶液,观察其对ICR小鼠自主活动的影响,协同戊巴比妥钠对小鼠的催眠作用;ELASA法测定脑匀浆液中GABA、5-HT含量。结果龙胆碱高、低(200 mg/kg、50 mg/kg)均能减少小鼠自主活动次数(P<0.05),增加阈下剂量戊巴比妥钠致小鼠入睡的只数并延长小鼠睡眠时间,龙胆碱能够增加脑内GABA含量,但对5-HT含量无影响。结论龙胆碱具有良好的镇静、催眠作用,其作用与增加脑内GABA含量有关。     

怡欣乐口服液镇静催眠及抗惊厥作用研究

目的研究中药复方制剂怡欣乐口服液(YXL)治疗失眠的作用机理。方法通过YXL对实验小鼠自发活动的影响,对戊巴比妥钠阈下剂量、阈剂量小鼠睡眠时间和对硝酸士的宁致小鼠惊厥的影响,研究YXL镇静、催眠、抗惊厥作用。结果YXL能抑制小鼠自发活动,对小鼠睡眠的影响与戊巴比妥钠有协同作用,有对抗硝酸士的宁致惊厥发作的作用,且剂量越大,作用越明显。结论YXL有明显的镇静、催眠、抗惊厥作用;本实验为YXL的临床运用提供了药效学方面的实验依据。     

中药镇静催眠作用机制的研究进展

失眠是一种由多种因素导致的常见睡眠障碍性疾病。目前治疗失眠的方法多种多样,其中化学药治疗失眠存在诸多不良反应。中药在治疗疾病方面,可以通过多成分、多靶点之间相互的协同作用,减轻单一成分产生的不良反应,具有更好的安全性和疗效,被广泛应用于治疗失眠。基于中医药理论结合失眠的发病机制,对近年来具有镇静催眠作用的单味中药及中药复方作用机制加以梳理概括,为临床失眠的治疗用药提供参考。     

Studies on the sedative effect of Cistanche deserticola

In this study, we investigated the sedative effect of Cistanche deserticola Ma. (CD) on hexobarbital-induced sleeping time in mice and spontaneous motor activity by using automated activity meter in rats. It was found that crude extract of CD could prolong the hexobarbital-induced sleeping time and reduce spontaneous motor activity, including horizontal activity, ambulatory time and total distance. Then the water fraction of CD extract could prolong the hexobarbital-induced sleeping time and reduce the spontaneous motor activity more than that of the other fraction of CD extract in rats. These results suggest that CD ethanol extract and its water fraction possessed the sedative effect.     

天王补心丸镇静安神作用的研究

目的:观察天王补心丸镇静催眠的药理作用。方法:选用ICR小鼠,随机分为5组:天王补心丸高、中、低剂量组,空白对照组,安神健脑液组。天王补心丸剂量组分别在(生药)3.24,1.62,0.81 g.kg-1剂量下连续ig给药7 d,测定药物对正常和阴虚模型小鼠自主活动的影响,以及对阈下、阈剂量戊巴比妥钠对催眠作用的影响。结果:测定5 min内小鼠自主活动数/次、睡眠率/%、睡眠潜伏期、维持睡眠时间。小鼠ig天王补心丸,对正常小鼠的自主活动没有明显影响,但能减少阴虚模型小鼠自主活动次数。对戊巴比妥钠所致睡眠有一定的协同作用,缩短小鼠睡眠潜伏期,延长小鼠睡眠时间。结论:天王补心丸具有一定的镇静安神作用。     

灵芝生料酿制液镇静催眠作用的研究

目的考察灵芝生料酿制液(GLB)镇静催眠药理作用。方法取NIH小鼠连续灌胃0.06,0.12,0.24g/kgGLB15d,测定GLB对实验小鼠自发活动情况,对戊巴比妥钠阈下剂量、阈剂量小鼠睡眠时间和对戊四氮致小鼠惊厥的作用。结果GLB灌胃可减少小鼠自发活动,显著延长阈上剂量戊巴比妥钠致小鼠睡眠时间,增加阈下剂量戊巴比妥钠睡眠动物数,GLB与戊巴比妥钠有协同作用。有对抗戊四氮致惊厥发作的作用,且剂量越大,作用越明显。结论GLB有明显的镇静、催眠、抗惊厥等中枢抑制作用。     

半夏秫米汤镇静催眠作用的实验研究

目的:观察半夏秫米汤的镇静催眠作用,并探讨量效关系。方法:将40只昆明种小鼠随机分为正常组、地西泮组及半夏秫米汤低剂量组、中剂量组、高剂量组(原方剂量),每组8只。正常组按剂量0.1 mL/10 g给予生理盐水灌胃,地西泮组按剂量0.75 mg/kg给予地西泮水溶液灌胃,其余各给药组按剂量6.75 g/kg、13.5 g/kg、27 g/kg给予半夏秫米汤灌胃,每日1次,连续7 d。末次灌胃给药后以自主活动仪观察小鼠自主站立次数,协同阈下/阈上剂量戊巴比妥钠催眠实验观察小鼠入睡率、睡眠潜伏期及睡眠时间。结果:与正常组比较,半夏秫米汤各剂量组小鼠自主站立次数减少(P0.05或P0.01),且入睡率升高;半夏秫米汤中、高剂量组睡眠时间延长,睡眠潜伏期缩短(P0.05或P0.01)。结论:半夏秫米汤具有良好的镇静催眠作用,呈量效关系,以原方剂量效果最佳。     

健脑安神胶囊对失眠大鼠EEG、EOG、EMG的睡眠时相及安全性的相关实验研究

目的:观察健脑安神胶囊对失眠大鼠睡眠时相及肝、肾功能的影响。方法:将80只Wister大鼠,随机分为假手术组、模型组、中药模型治疗组、西药模型治疗组各20只,采用对氯苯丙氨酸(PCPA)腹腔注射复制失眠大鼠模型,各组灌胃治疗3周,治疗前后监测各组大鼠脑电图(EEG)、眼动电图(EOG)、肌电图(EMG)及肝、肾功能的变化。结果:中药模型治疗组与模型组相比觉醒期(Waking)明显缩短,慢波睡眠期(SWS)、快动眼睡眠(REMS)、总睡眠期(TST)明显回升(P<0.01)。比较4组治疗前后尿素氮、肌酐、谷丙转氨酶、谷草转氨酶,无统计学意义(P>0.05)。结论:健脑安神胶囊治疗失眠的疗效确切,其治疗失眠的作用机制与减少失眠大鼠的觉醒时间,延长SWS、REMS、TST期有关。且该药物对大鼠肝肾功能无明显损害,具有良好的药物安全性。     

Antinociceptive and hypnotic properties of Celastrus orbiculatus

Ethnopharmacological relevance

Celastrus orbiculatus, a woody vine of the Celastraceae family, has been widely used as a traditional medicine for the treatment of many diseases, including rheumatoid arthritis and odontalgia. In this study, we assessed the sedative and antinociceptive activities of the methanolic extract of Celastrus orbiculatus (MCO).

Materials and methods

The antinociceptive effect of MCO was evaluated using several experimental pain models, including thermal nociception methods, such as the tail immersion and the hotplate tests, as well as chemical nociception induced by intraperitoneal acetic acid and subplantar formalin administration in mice. To verify the possible connection of the opioid receptor to the antinociceptive activity of MCO, we performed a combination test with naloxone, a nonselective opioid receptor antagonist. The sedative effect of MCO was studied using the pentobarbital-induced sleeping model.

Results

MCO demonstrated strong and dose-dependent antinociceptive activity compared to tramadol and indomethacin in various experimental pain models. The combination test using naloxone revealed that the antinociceptive activity of MCO is associated with activation of the opioid receptor. MCO also caused decreased sleep latency and increased sleeping time in the pentobarbital-induced sleeping model; however, MCO alone did not induce sleep.

Conclusions

In the present study, MCO showed potent antinociceptive and sedative activities. Based on these results, MCO may be considered a valuable anti-nociceptive and hypnotic agent for the treatment of various diseases.