l-THP对大鼠甲基苯丙胺对条件位置偏爱效应的影响

目的：研究左旋四氢巴马汀(l—tetrahydropalmatine，l—THP)对甲基苯丙胺诱导的大鼠条件位置偏爱(conditioned place preference．CPP)模型的干预作用，并初步探讨其神经生化机制。方法：结果：通过条件位置偏爱实验建立大鼠甲基苯丙胺精神依赖模型，用左旋四氢巴马汀和多巴胺受体拮抗剂干预模型的消退、重建过程，比较分析各组实验结果。CPP实验中大鼠对甲基苯丙胺有明显的偏爱效应，但大鼠腹腔注射l—THP未显示明显的偏爱效应．l—THP对实验大鼠不能诱导条件位置偏爱效应。l—THP能不同程度地促进甲基苯丙胺诱导的大鼠条件位置偏爱效应的消退．而且这一作用有可能呈现一定的剂量依赖性，而且可以在一定程度上抑制低剂量甲基苯丙胺引起的大鼠CPP效应的重建。结论：l—THP在大鼠甲基苯丙胺精神依赖CPP实验中能够影响模型的表达、消退、重建过程。而l—THP在CPP实验中却没有显示出依赖性潜力。     

左旋四氢巴马汀对苯丙胺条件性位置偏爱效应的影响

目的　观察左旋四氢巴马汀 (l-tetrahydropalmatine ,l-THP)对苯丙胺 (Amphetamine,AA)的条件性位置偏爱 (conditionalplacepreference,CPP)效应的影响。方法　采用倾向性训练程序训练大鼠 ,建立位置偏爱模型和建立氢化可的松诱发位置偏爱效应重现模型 ,并观察l-THP对其影响。结果　l-THP 10mg·kg-1可阻断AA 2 .0mg·kg-1的位置偏爱效应 ,并且可阻止氢化可的松 10mg·kg-1诱发的位置偏爱效应的重现。结论　AA可使大鼠出现条件性位置偏爱效应 ,并在一定剂量范围内 (0 .5～ 4.0mg·kg-1)呈量效关系 (r=0 .94) ;氢化可的松可使已消失的位置偏爱效应重现 ;以上 2种效应均可被l-THP阻断。     

左旋四氢巴马汀对大鼠离体子宫收缩反应的影响

目的:研究左旋四氢巴马汀(l-THP)对大鼠离体子宫收缩反应的影响.方法:采用离体子宫平滑肌实验法.结果:l-THP对高钾去极化后Ca2 引起的子宫收缩有显著松弛作用,并能使CaCl2的量效曲线右移,最大反应降低.l-THP(50～300μmol/L)剂量依赖性拮抗缩宫素(1.5u/L)所致的子宫收缩;在无Ca2 高钾液中,l-THP 100μmol/L能抑制缩宫素依赖细胞内Ca2 的收缩;而l-THP 300μmol/L对缩宫素依赖细胞外Ca2 的收缩亦有抑制作用.结论:l-THP对大鼠子宫平滑肌的收缩反应具有明显拮抗作用.     

Effects of l-tetrahydropalmatine on locomotor sensitization to oxycodone in mice

Aim: Recent studies have shown that l-tetrahydropalmatine (l-THP), an active component of Corydolis yanhusuo, can inhibit the development of the conditional place preference induced by opioid receptor agonists, but the effects of l-THP on locomotor sensitivity induced by opioid receptor agonists have not been documented. In the present study, the effects of l-THP on locomotor sensitization to oxycodone, which is an opioid receptor agonist, were studied. Methods: Mice treated daily for 7d with 5mg/kg oxycodone and challenged with the same dose after 5 days of washout showed locomotor sensitization. In order to study the effects of l-THP on locomotor sensitization induced by oxycodone, l-THP was administered at doses of 6.25, 12.5, and 18.75mg/kg, 40min prior to treatment of oxycodone. Results: l-THP per se did not affect the locomotor activity at the doses of 6.25, 12.5, and 18.75mg/kg, but could antagonize the hyperactivity induced by oxycodone (5mg/kg). Co-administration of l-THP (18.75mg/kg), 40min prior to oxycodone, could inhibit the development of sensitization to oxycodone.In addition, l-THP (6.25, 12.5, and 18.75mg/kg, ig) dose-dependently prevented the expression of oxycodone sensitization. Conclusion: These results suggested that l-THP could attenuate the locomotor-stimulating effects of oxycodone and inhibit the development and expression of oxycodone behavioral sensitization.     

左旋四氢巴马汀和左旋千金藤啶碱对吗啡处理大鼠相关脑区神经胶质纤维酸性蛋白的影响

目的：研究慢性吗啡处理大鼠相关脑区神经胶质纤维酸性蛋白（GFAP）的改变，以及左旋四氢巴马汀和左旋千金藤啶碱的干预作用。方法：以剂量递增给药方式建立吗啡慢性依赖模型后分别给予左旋四氢巴马汀、左旋千金藤啶碱和等体积蒸馏水（作为自然戒断组）治疗30d。制备相关脑区的冰冻切片，进行GFAP的免疫组织化学染色，测定阳性细胞的平均吸收度。结果：自然戒断组大鼠前额叶皮质、伏隔核壳区、海马CA．区、黑质、杏仁核的GFAP表达与正常对照组无显著差异，但中脑腹侧背盖区（VTA）GFAP表达较正常对照组显著升高。左旋四氢巴马汀及左旋千金藤啶碱组大鼠脑VTA区GFAP表达较自然戒断组均显著降低，且可达到正常水平。结论：GFAP表达持续升高反映吗啡处理对VTA区的损伤，左旋四氢巴马汀及左旋千金藤啶碱可以使GFAP表达恢复正常，可能是它们对成瘾药物的精神依赖性有干预作用的机制之一。     

左旋四氢巴马汀对大鼠甲基苯丙胺辨别行为的影响

研究左旋四氢巴马汀 (l-THP)对药物精神依赖性的影响。方法··:用固定比率食物强化方法使大鼠对甲基苯丙胺 (MA)形成稳定的辨别效应。以多巴胺受体拮抗剂Sch -23390和螺哌隆拮抗MA效应 ,观察辨别效应的变化 ;以l-THP替代及对抗MA效应 ,并观察其对大鼠MA辨别行为重建的影响。结果·· :大鼠对MA形成稳定的辨别 ;0.001mg·kg-1Sch -23390及0.01mg·kg-1螺哌隆均拮抗训练剂量MA的辨别效应 ;5mg.kg-1l-THP不能替代训练剂量MA ,但能阻断其辨别效应 ;l-THP明显降低大鼠MA辨别行为重建时的踏杆正确率 (P<0.05)。结论·· :MA可使大鼠形成稳定的辨别效应 ,而且DA受体参与调控MA的这种效应 ;l-THP能阻断MA辨别行为 ,影响MA辨别行为的重建 ,表明其可降低MA精神依赖性的形成。     

左旋四氢巴马汀对门静脉压的影响及其机制

为探讨左旋四氢巴马汀（ｌ－ｔｅｔｒａｈｙｄｒｏｐａｌｍａｔｉｎｅ，ｌ－ＴＨＰ）对门静脉压的影响及可能机理，观察ｌ－ＴＨＰ对正常大鼠和利血平化大鼠门静脉压的作用，并与哌唑嗪比较。结明表明：ｌ－ＴＨＰ使正常大鼠门静脉压下降２９．７９±９．７８％（Ｐ＜０．０１），并拮抗苯肾上腺素升高门静脉压的作用。大鼠利血平化后，哌唑嗪不再降低门静脉压，而ｌ－ＴＨＰ仍使门静脉压下降１５．９８±５．１７％（Ｐ＜０．０５）。提示α１受体阻断作用是ｌ－ＴＨＰ降低门静脉压的主要机理之一，α１受体以外降门静脉压机理亦共同参与作用。     

l-千金藤立定——应用于麻醉期的镇静药

l-千金藤立定作为镇静药应用于麻醉期间,麻醉方法包括针麻、臂丛阻滞及硬脊膜外阻滞等,共107例。肌注25mg后20min左右,94％病人安静,84％嗜睡。在针麻及臂丛阻滞病人中,血压、心率无明显改变,但于硬脊膜外阻滞下施行上腹部手术时,血压明显下降4.0±SD2.5kPa(30±19mmHg),心率减慢。与四氢巴马丁60mg相比,后者血压下降较轻2.0±1.6kPa(15±12mmHg)。剖腹探查时,40％病人恶心、呕吐仍不能消除,有2例出现精神症状。     

Ethnobotany,phytochemistry and pharmacology of Stephania rotunda Lour

Ethnopharmacological relevance

Stephania rotunda Lour. (Menispermaceae) is an important traditional medicinal plant that is grown in Southeast Asia. The stems, leaves, and tubers have been used in the Cambodian, Lao, Indian and Vietnamese folk medicine systems for years to treat a wide range of ailments, including asthma, headache, fever, and diarrhoea. Aim of the review: To provide an up-to-date, comprehensive overview and analysis of the ethnobotany, phytochemistry, and pharmacology of Stephania rotunda for its potential benefits in human health, as well as to assess the scientific evidence of traditional use and provide a basis for future research directions.

Material and methods

Peer-reviewed articles on Stephania rotunda were acquired via an electronic search of the major scientific databases (Pubmed, Google Scholar, and ScienceDirect). Data were collected from scientific journals, theses, and books.

Results

The traditional uses of Stephania rotunda were recorded in countries throughout Southeast Asia (Cambodia, Vietnam, Laos, and India). Different parts of Stephania rotunda were used in traditional medicine to treat about twenty health disorders. Phytochemical analyses identified forty alkaloids. The roots primarily contain l-tetrahydropalmatine (l-THP), whereas the tubers contain cepharanthine and xylopinine. Furthermore, the chemical composition differs from one region to another and according to the harvest period. The alkaloids exhibited approximately ten different pharmacological activities. The main pharmacological activities of Stephania rotunda alkaloids are antiplasmodial, anticancer, and immunomodulatory effects. Sinomenine, cepharanthine, and l-stepholidine are the most promising components and have been tested in humans. The pharmacokinetic parameters have been studied for seven compounds, including the three most promising compounds. The toxicity has been evaluated for liriodenine, roemerine, cycleanine, l-tetrahydropalmatine, and oxostephanine.

Conclusion

Stephania rotunda is traditionally used for the treatment of a wide range of ailments. Pharmacological investigations have validated different uses of Stephania rotunda in folk medicine. The present review highlights the three most promising compounds of Stephania rotunda, which could constitute potential leads in various medicinal fields, including malaria and cancer.