Inhibiting Activity of Some Glucoindolalkaloids and Iridoids from Sickingia williamsii on Electrically Induced Contractions of Isolated Guinea-pig Ileum

The present study examined the effects of the extracts (petroleum ether, CHCl₃, CHCl₃/MeOH (9:1) and MeOH), partially purified fractions and pure compounds (mainly alkaloids and iridoids) from Sickingia williamsii on the electrically induced contractions of the isolated guinea-pig ileum. The results of our experiments indicate that CHCl₃/MeOH (9:1) and CHCl₃ extracts, tested at concentrations of 300, 150 and 30 μg/mL, dose-dependently reduced the guinea-pig ileum electrical contractions, whereas MeOH and petroleum ether extracts did not affect it. Furthermore, both the partially purified fractions I–IV each tested at concentrations of 500, 250 and 100 μg/mL from the CHCl₃/MeOH (9:1) extract and some pure compounds (10⁻⁴ M , 5×10⁻⁵ M and 2.5×10⁻⁵ M ) isolated and purified from the above fractions significantly reduced, in a dose dependent manner, the electrical contractions of the ileum. As the active pure compounds possess an indole nucleus or/and an iridoid nucleus in their structures, the inhibitory effects appear to depend on these structures.     

电针缓解吗啡戒断大鼠的心动过速

目的：建立吗啡戒断大鼠心动过速模型，观察不同频率电针对其心率的影响。方法：给大鼠连续注射递增量吗啡８天，造成其对吗啡依赖。停药后１８～２４ｈ给于强度为１ｍＡ，频率为２Ｈｚ、１５Ｈｚ、１００Ｈｚ的电针刺激，记录清醒状态下吗啡戒断大鼠的心率和血压。结果：与正常大鼠比较吗啡戒断大鼠心率显著增快（Ｐ〈０．０１），但平均动脉压无显著性差异。１５Ｈｚ和１００Ｈｚ电针对吗啡戒断大鼠的心动过速均有显著抑制作用（使     

Alkaloids from Brugmansia arborea (L.) Lagerhein reduce morphine withdrawal in vitro

Traditional medicine is a primary source for the study of medicinal plants. In some countries, knowledge about the therapeutic use of medicinal plants is very deep and very often 'magical' plants also are used to diagnose and treat illnesses. The study of these plants can help in the research of metabolites active on the central and peripheral nervous system. Brugmansia arborea (L.) Lagerheim (Solanaceae) is used in the northern Peruvian Andes for magic-therapeutic purposes and the present study examined the effect of three pure tropane alkaloids from Brugmansia arborea (L.) Lagerhein (Solanaceae) on morphine withdrawal in vitro. All the tropane alkaloids isolated from Brugmansia arborea (L.) (10(-7), 5 x 10(-7), 10(-6) m) significantly and in a concentration dependent manner reduced morphine withdrawal. The results of the present study suggest that these alkaloids may be a potential anti-additive agent.     

电针对吗啡戒断大鼠cAMP、cGMP水平的影响

目的研究电针吗啡戒断大鼠足三里穴对大鼠环磷鸟苷酸(cyclic guanosine3',5'-monophosphate,cGMP)及环磷腺苷酸(cyclic adenosine3',5'-monophosphate,cAMP)含量的影响,探讨电针改善戒断症状作用的可能机制。方法建立吗啡依赖大鼠自然戒断模型,采用放射免疫分析法测定血液、脑组织中cGMP、cAMP含量。结果戒断Ⅰ组大鼠血液cAMP含量增高(P<0.01),cGMP含量明显降低(P<0.01),cAMP/cGMP比值显著增高(P<0.01);戒断Ⅱ组大鼠脑中cGMP、cAMP含量均明显减少(P<0.01);电针组cGMP、cAMP含量接近正常水平。结论电针足三里穴改善大鼠吗啡戒断症状可能与调节cGMP、cAMP系统的相互作用有关。     

Inhibitory Effect of Bacopasides on Spontaneous Morphine Withdrawal Induced Depression in Mice

Bacopa monnieri is a perennial herb with a world known image as a nootropic. We investigated the effect of Bacopa monnieri methanolic extract (Mt Ext BM) 10, 20, and 30 mg/kg body weight (b.w) on acquisition and expression of morphine withdrawal induced depression in mice. Locally available Bacopa monnieri (BM) was screened for contents of Bacoside A₃, Bacopasaponin C, and Bacopaside II using HPLC with UV. Morphine dependence was induced in mice using twice daily escalating chronic morphine treatments (20–65 mg/kg b.w) for eight consecutive days. Morphine withdrawal induced depression was assayed in animals using forced swimming test (FST), three days after last morphine injection. The HPLC analysis revealed that Mt‐ext BM contained Bacoside A₃ as major component, i.e. 4 µg in each mg of extract. The chronic treatment with Met Ext BM 10, 20, and 30 mg/kg b.w. dosing significantly inhibited opioid withdrawal induced depression in mice. These findings imply a newer potential role of Bacopa monnieri in the clinical management of opioid withdrawal induced depression which can be attributed to Bacoside A₃. Copyright © 2013 John Wiley & Sons, Ltd.     

电针足三里对吗啡戒断大鼠μ受体mRNA表达的影响

目的探讨电针改善吗啡戒断症状的作用机制。方法建立自然吗啡戒断大鼠模型，运用RT—PCR方法测定脑组织μ受体mRNA的表达，观察电针足三里对吗啡戒断大鼠体重及μ受体mRNA表达的影响。结果电针组大鼠体重比戒断组增加明显（P〈0．05），戒断组和电针组比正常组脑组织中μ受体mRNA表达降低，治疗后电针组比戒断组脑组织中μ受体mRNA表达明显增加。结论电针足三里具有提高吗啡戒断大鼠体重、改善大鼠吗啡戒断症状的作用。电针调节吗啡戒断大鼠海马、下丘脑μ受体mRNA的表达，可能是电针改善大鼠吗啡戒断症状的作用机制之一。     

吗啡依赖大鼠额叶皮质内神经甾体水平的变化

 目的探讨吗啡依赖和戒断对雄性大鼠额叶皮质内神经甾体水平的影响。方法腹腔注射递增剂量吗啡建立大鼠吗啡躯体依赖模型,纳洛酮诱发戒断症状;条件性位置偏爱实验建立吗啡精神依赖模型。高效液相色谱-质谱法测定大鼠额叶皮质和血浆中脱氢表雄酮(DHEA)及其硫酸酯(DHEAS)、孕烯醇酮(PREG)及其硫酸酯(PREGS)和别孕烯醇酮(AP)的含量。结果与对照组比较,大鼠吗啡躯体依赖形成时额叶皮质内DHEA水平显著升高(P<0.05),精神依赖形成时额叶皮质内DHEA,PREG水平显著升高(P<0.05);与纳洛酮对照组比较,纳洛酮催促吗啡戒断时大鼠额叶皮质内PREG,AP的含量显著升高(P<0.01),DHEAS水平显著降低(P<0.05)。结论吗啡依赖、戒断可影响大鼠额叶皮质内某些神经甾体的水平,表明内源性神经甾体可能参与吗啡依赖的形成。     

电针对吗啡戒断后焦虑小鼠脑干c—fos表达的影响

目的：探讨电针对吗啡戒断后焦虑小鼠脑干c—fos表达的影响。方法：以昆明种小鼠为实验对象,采用逐日递增原则皮下注射吗啡形成依赖后,纳洛酮催促,建立吗啡戒断后焦虑模型;选用“三阴交”穴进行电针治疗;每天1次,每次15min,连续治疗3天。免疫组化法检测c—fos的表达。结果：与模型组相比,模针组脑干c—fos光密度值、阳性细胞数、阳性面积百分比下降,灰度值增高,差异均有统计学意义（P〈0．01）,与迷空组相比,则无明显差异。结论：电针抗吗啡戒断后焦虑效应可能与其降低脑干c—fos的表达有关。     

电针对吗啡戒断大鼠胸腺细胞凋亡相关基因的影响

目的:探讨电针抗吗啡戒断大鼠胸腺细胞凋亡的作用机制。方法:40只SD大鼠随机分为正常组、对照组、依赖组、电针组,连续20d递增量肌肉注射吗啡造成吗啡成瘾模型。造模后,依赖组立刻处死;对照组观察7d后处死;电针组电针双侧"足三里"穴(2/100Hz,2~4mA),每日1次,每次30min,治疗7d后处死。取大鼠胸腺,用免疫组化法检测凋亡基因Bcl-2、Bax、Fas、FasL蛋白表达。结果:与正常组比较,对照组和依赖组Bcl-2表达明显减少,Bax明显增加(P<0.01);电针组与对照组相比,Bcl-2表达上升(P<0.05),Bax表达的下降尚未达到统计学意义(P>0.05)。对照组及依赖组Fas、FasL的表达比正常组明显升高(P<0.01);电针组与对照组相比,Fas、FasL的表达均明显减少,差异显著(P<0.01)。结论:电针"足三里"穴增加吗啡戒断大鼠胸腺细胞内Bcl-2蛋白表达的水平,减少Bax蛋白表达水平,降低Bax/Bcl-2比值,抑制Fas、FasL表达水平的提高,可能是电针抗吗啡戒断大鼠胸腺细胞凋亡的作用机制之一。     

参附注射液对吗啡依赖大鼠或断症状的治疗作用

目的：观察参附注射液对吗啡依赖大鼠戒断症状的治疗作用。方法：将大鼠随机分为正常对照组（A组）、停用吗啡组（B组）、续用吗啡组（C组）、丁内诺啡组（D组）和参附注射液低，高剂量组（E组、F组），按剂量递增方法腹腔注射吗啡制成吗啡依赖模型并分别给予不同药物后，腹腔注射盐酸纳洛酮催瘾，观察大鼠的戒断症状，体重及单胺类神经递质水平的变化。结果：经参附注射液治疗的大鼠戒断症状明显减轻，体重明显恢复，脑组织中NA、DA、5－HT等单胺类神经递质水平显著降低，结论：参附注射液对吗啡依赖大鼠具有一定治疗作用，其机理与调节单胺类神经递质的紊乱有关。     

Phytotherapy of Opioid Dependence and Withdrawal Syndrome: A Review

Development of tolerance and dependence is a major problem associated with opioid treatment. Withdrawal syndrome is common between medical and illicit users of these agents. Phytomedicine has shown promise in the treatment of this complicated psychosomatic condition. In this study, the effects of plant extracts and active components on morphine dependence and withdrawal syndrome are discussed. Proper keywords were used to search through PubMed, Google Scholar, and SciVerse, as well as two local scientific databases, www.iranmedex.com and www.SID.com . All relevant results (original articles, meeting abstracts, patents, etc.) published from 2000 to 2013 were chosen for final review. A total of 35 plant species were studied on this subject. Plants from Lamiaceae, Ranunculaceae, and Apiaceae families were especially effective. A few studies were carried out on human subjects and the rest in animal models. Opioid dependence and withdrawal syndrome remain an intimidating challenge. Nonetheless, plants and their derivatives are suitable sources for their treatment. Although there are several plants shown to be effective in animal models, few clinical studies are available. Copyright © 2013 John Wiley & Sons, Ltd.     

药物依赖中草药戒断的应用研究进展

目的：综述国内外中草药用于药物依赖戒断的研究情况。方法：结合文献和资料,简述了药物依赖形成的中医理论解释。中药戒断的理论依据及近几年研究开发的代表方剂。结果和结论：中医药戒断药物依赖是目前研究开发戒毒药物的主要方向。     

参附汤加味对吗啡依赖大鼠戒断症状及位置偏爱效应的影响

以参附汤加味、丁丙诺啡对吗啡依赖大鼠进行脱毒治疗,观察其对湿狗样抖动、齿颤等戒断症状及位置偏爱效应的影响.结果表明参附汤与丁丙诺啡联合应用能有效地缓解和控制戒断症状,递减顺利,但不能影响位置偏爱效应,推测亦不能减轻大鼠对阿片类药物的渴求感.     

电针抗吗啡戒断后焦虑的5-HT_(1A)受体作用机理研究

目的:探讨电针抗吗啡戒断后焦虑的5-HT1A受体作用机理。方法:建立吗啡依赖戒断小鼠模型,分别予模型小鼠皮下连续注射5-HT1A受体激动剂(8-OH-DPAT)或拮抗剂(WAY-100635),并予电针治疗后,以高架十字迷宫测试小鼠焦虑情绪。结果:(1)电针和8-OH-DPAT均可提高模型小鼠的OT%和OE%值(P<0.05)。(2)电针可明显提高注射WAY-100635的模型小鼠的OT%和OE%值(P<0.05)。结论:5-HT1A受体在抗焦虑过程中起重要作用,它可能是电针抗焦虑的重要中枢作用途径之一。     

Standardized Passiflora incarnata L. Extract Reverts the Analgesia Induced by Alcohol Withdrawal in Rats

Passiflora incarnata L. (Passifloraceae) has been traditionally used for treatment of anxiety, insomnia, drug addiction, mild infections, and pain. The aim of this study was to investigate the effect of a commercial extract of P. incarnata in the analgesia induced by alcohol withdrawal syndrome in rats. In addition, brain‐derived neurotrophic factor and interleukin‐10 levels were evaluated in prefrontal cortex, brainstem, and hippocampus. Male adult rats received by oral gavage: (1: water group) water for 19 days, 1 day interval and water (8 days); (2: P. incarnata group) water for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days); (3: alcohol withdrawal group) alcohol for 19 days, 1 day interval and water (8 days); and (4: P. incarnata in alcohol withdrawal) alcohol for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days). The tail‐flick and hot plate tests were used as nociceptive response measures. Confirming previous study of our group, it was showed that alcohol‐treated groups presented an increase in the nociceptive thresholds after alcohol withdrawal, which was reverted by P. incarnata, measured by the hot plate test. Besides, alcohol treatment increased brain‐derived neurotrophic factor and interleukin‐10 levels in prefrontal cortex, which was not reverted by P. incarnata. Considering these results, the P. incarnata treatment might be a potential therapy in the alcohol withdrawal syndrome. Copyright © 2017 John Wiley & Sons, Ltd.     

电针对吗啡戒断大鼠杏仁核内N-甲基-D-天门冬氨酸受体亚单位NR2B蛋白及基因表达的影响

目的:观察电针对吗啡戒断大鼠空间学习记忆的影响,通过对杏仁核脑区N-甲基-D-天门冬氨酸受体亚单位NR 2B表达的检测,探讨电针改善大鼠吗啡戒断后学习记忆能力的分子生物学机制。方法:雄性SD大鼠,随机分为空白组、模型组、针刺组以及电针组,每组10只。以每日20,30,40,50,50mg/kg剂量,连续5d背部皮下注射盐酸吗啡,建立吗啡依赖大鼠模型,末次注射后3h给予纳洛酮快速戒断。两个治疗组选取"足三里""肾俞"穴分别施以手针和电针,每次15min,每日1次,连续治疗6d。应用Morris水迷宫测试戒断大鼠空间学习能力,应用蛋白印记(Western blot)及实时荧光定量聚合酶链反应(RT-PCR)技术检测戒断大鼠杏仁核NR 2B蛋白与基因的表达水平。结果:模型组大鼠的逃避潜伏期较空白组明显延长(P0.01),针刺及电针组则较模型组显著缩短(P0.01),电针组较针刺组缩短更明显(P0.05);模型组大鼠的杏仁核NR 2B蛋白表达较空白组显著降低(P0.01),针刺组、电针组则较模型组表达升高(P0.01),电针组高于针刺组(P0.01);模型组NR 2BmRNA表达较空白组显著降低(P0.01),电针组较模型组表达升高(P0.05)。结论:吗啡戒断后大鼠空间学习能力受损,针刺及电针可以恢复大鼠学习能力且电针组疗效优于针刺组,推测可能与其对杏仁核NR 2B表达的调节有关。     

RP-HPLC测定洋参保肺糖浆中吗啡的含量

目的对洋参保肺糠浆中有效成分吗啡含量进行测定.方法HPLC,以0.1mol/L磷酸二氢钠溶液-甲醇(5∶1)为流动相,采用Kromasil C18分析柱(250×4.6mm,5μm)对制剂中吗啡的含量进行测定.结果该方法的线性范围为0.68-3.9 μg(r=0.998),平均回收率为97.4%(RSD=0.98%).结论可作为产品的质量分析方法.     

高效液相色谱法测定强力枇杷露中吗啡的含量

目的建立强力枇杷露中吗啡的含量测定方法。方法采用HPLC法,C8柱(150mm×4.6mm,5μm),以乙腈-0.01moL?L-1磷酸氢二钾溶液-0.005moL?L-1庚烷磺酸钠溶液(19:41:40)为流动相,检测波长为220nm;柱温25℃,流速1.0mL?min-1。结果吗啡在5.015～80.240μg?mL-1范围内线性关系良好(r=0.9999),平均回收率97.95%,RSD=1.0%(n=6)。结论本方法操作简便、重现性好;可准确测定强力枇杷露中吗啡的含量。     

HPLC法测定橘红化痰胶囊中吗啡的含量

目的建立橘红化痰胶囊中吗啡的含量测定方法。方法采用HPLC法,ODS-C18色谱柱(4.6mm×200mm,5μm);以乙腈acetonitrile-0.01mol/L磷酸氢二钾溶液-0.005mol/L庚烷磺酸钠水溶液(18:42:40)为流动相movingphase;检测波长为220nm;进样量10μL。结果吗啡在0.04816-0.43344μg/mL范围内与其峰面积呈良好的线性关系(r=0.9998),加样回收率为98.63%(RSD为0.84%,n=6)。结论本方法具有操作简便、分离度、精密度、重复性好,回收率高、重现性好等特点,可以作为橘红化痰胶囊中吗啡的含量测定方法。     

参附注射液对吗啡依赖大鼠戒断症状及单胺类神经递质的影响

目的：观察参附注射液对吗啡依赖大鼠的戒毒作用。方法：雄性大鼠按剂量递增方法ip吗啡形成吗啡依赖模型,ip盐酸纳洛酮（1.0mg/kg）催瘾,观察戒断症状、体重及单胺类神经递质变化。结果：参附注射液能减轻大鼠的症状,恢复体重,显降低吗啡依赖大鼠催促戒断时脑组织中NA、DA、5－HT等单胺类神经递质。结论：参附注射液对吗啡依赖大鼠具有一定治疗作用,其机理与调节单胺类神经递质紊乱有关。