吴茱萸化学拆分组分的性味药理学评价——化学拆分组分止泻、止呕作用的研究

目的:阐明吴茱萸化学拆分组分与止泻、止呕作用的关系,为阐明吴茱萸性味的物质基础,进而为"中药一味一性,一药X味Y性(Y≤X)"的中药性味理论新假说的客观性提供科学依据。方法:采用番泻叶致小鼠腹泻实验、豚鼠离体回肠作用实验、家鸽止呕实验考察了吴茱萸水煎液及其性味拆分组分(吴茱萸内酯单体、生物碱1组分、生物碱2组分、醇沉组分、20%乙醇洗脱组分、95%乙醇洗脱组分和挥发油组分)的止泻、止呕作用。结果:吴茱萸水煎液、吴茱萸内酯组分、生物碱2组分及95%乙醇洗脱组分有止泻作用(P<0.05);吴茱萸水煎液及生物碱2组分有止呕作用(P<0.05)。结论:吴茱萸具有一定止泻、止呕作用,吴茱萸化学拆分组分中的吴茱萸内酯组分、生物碱2组分及95%乙醇洗脱组分是其发挥止泻、止呕作用的物质基础。     

止呕合剂对猫化疗后体内5-HT和NO含量的影响

目的 :研究DDP诱发呕吐的胃肠道机制和止呕合剂对其的作用。方法 :记录 30只猫的呕吐发生率 ,并用生物化学分析法测定 5 -HT和NO含量。结果 :DDP增加了呕吐发生率 ,提高体内 5 -HT的含量 ,减少NO的含量 ;止呕合剂降低了呕吐发生率 ,减少 5 -HT的含量 ,提高NO的水平。中药组血、胃肠组织中 5 -HT、5 -HIAA浓度都较NS组明显下降而NO水平却明显高于NS组。认为 ,DDP致呕与胃肠组分泌 5H增多、NO减少有关。结论 :DDP诱发呕吐的机制与其提高5 -HT水平 ,降低NO水平有关 ,止呕合剂的胃肠道机制与其降低 5 -HT水平 ,提高NO水平有关。     

综合评分法优化吴茱萸中5种活性成分的提取工艺

目的:优选吴茱萸中五种活性成分的提取工艺。方法:以绿原酸、去氢吴茱萸碱、吴茱萸内酯、吴茱萸碱、吴茱萸次碱含量的综合评分为指标,用HPLC法测定,采用单因素实验结合正交实验考察乙醇体积分数、提取方式、液料比、提取时间和提取次数对提取工艺的影响。结果:吴茱萸中5种活性成分的最佳提取工艺为原药材中加入50倍量的70%乙醇,超声提取3次,每次30min。结论:优选的提取工艺合理、稳定、可行。     

合欢皮不同提取组分对HMEC细胞和3B11细胞的作用研究

目的探究合欢皮不同提取组分抗肿瘤新生血管的作用。方法采用有机溶剂萃取,大孔树脂梯度洗脱,获取所用实验组分,SRB染色法在HMEC细胞和3B11细胞上进行活性筛选和半数抑制率(IC50)的测定,比较不同提取组分抗肿瘤新生血管作用的强弱。结果不同工艺路线所得组分的得率为:水提醇沉法所得醇溶部分冻干粉经正丁醇萃取后正丁醇相(组分1)1.35%;大孔树脂吸附水洗脱组分(组分2)1.49%,30%乙醇洗脱组分(组分3)1.24%,50%洗脱组分(组分4)0.81%,70%洗脱组分(组分5)0.32%。各组分的皂苷反应均为阳性。活性评价结果:只有组分1、组分4和组分5有活性,在HMEC细胞和3B11细胞的IC50分别为:7.20,2.92,4.59μg/ml和13.29,18.89,7.74μg/ml。结论不同工艺路线所得的活性组分,通过得率,活性,工艺路线简易程度比较,正丁醇萃取物是最理想的抑制肿瘤血管生长的有效组分。     

止呕中药防治化疗性恶心呕吐与其抗炎作用研究

研究发现,半夏、生姜、连翘、旋覆花等具有止呕作用的中药同时也具有较好的抗炎作用,推测上述中药可用于治疗肿瘤患者化疗后恶心呕吐(CINV)和胃肠道黏膜炎。半夏、生姜、连翘、旋覆花等止呕中药治疗CINV的机制主要是针对5-HT和SP等神经递质,通过阻断5-HT3受体和NK1受体从而发挥止呕作用。上述四味止呕中药同时具有显著的抗炎作用,大多是通过激活NF-κB通路,降低其介导的TNF-α、IL-1β、IL-6等炎性因子含量;抑制COX-2的活性和PGE2的释放与合成;抑制SP、5-HT等炎症介质的释放;降低氧化应激损伤,从而发挥抗炎作用。     

化胃舒颗粒对抗化疗药引起呕吐药效学实验研究及作用机制探讨

目的:研究化胃舒颗粒对硫酸铜、顺铂所致家鸽以及顺铂所致水貂的呕吐模型的止呕作用及其作用机制。方法:(1)以硫酸铜引起家鸽呕吐模型和顺铂引起家鸽呕吐模型为研究对象,观察该药对其的止呕作用;(2)以顺铂引起水貂呕吐模型为研究对象,观察该药对其的止呕作用、以及延髓及回肠中5-HT含量的影响;结果:(1)化胃舒颗粒可以延缓硫酸铜、顺铂引起家鸽呕吐的潜伏期、减少呕吐次数;(2)化胃舒颗粒可以延缓顺铂引起水貂呕吐的潜伏期、减少呕吐次数;降低水貂延髓及回肠中5-HT含量;结论:化胃舒颗粒对顺铂和硫酸铜所致呕吐模型有止呕作用,此作用可能与中枢和外周5-HT生成与释放有关。     

苦参中的止痒成分

对5-HT诱发的急性瘙痒以及类似特应性皮炎的慢性瘙痒模型动物,经口给予苦参提取物具有显著的止痒作用。本次对苦参提取物中的止痒成分进行了筛选。 方法:按照常法分离苦参甲醇提取物的生物碱组分和非生物碱组分,探讨各组分对皮内注射5-HT(100nmol/50mL)诱发搔痒行为的影响。然后再观察具有活性的组分对NC系小鼠慢性搔痒行为的影响。进一步经硅胶柱层析分离活性组分。 结果:皮内注射5-HT 1h前经口给予生物碱组分和非生物碱组分(20mg/kg),生物碱组分可减少搔痒行为,表明生物碱组分对NC系小鼠的慢性搔痒行为亦有抑制作用,其作用出现…     

吴茱萸化学拆分组分的性味药理学评价——化学拆分组分抗胃溃疡作用的研究

目的：阐明吴茱萸的化学拆分组分与抗胃溃疡作用的关系,为阐明吴茱萸的性味及其物质基础,进而为＂中药一味一性,一药X味Y性（Y≤X）＂的中药性味理论新假说的客观性提供科学依据。方法：以应激型胃溃疡实验、幽门结扎胃溃疡实验考察了吴茱萸水煎液及其性味拆分组分（吴茱萸内酯单体、生物碱1组分、生物碱2组分、醇沉组分、20%乙醇洗脱组分、95%乙醇洗脱组分和挥发油组分）的抗胃溃疡作用。结果：吴茱萸水煎液、挥发油组分、吴茱萸内酯组分、醇沉组分均能降低应激型胃溃疡的溃疡指数,与模型组比较有显著性差异（P〈0.05）;其余各化学拆分组分与模型组比较没有显著性差异（P〉0.05）。吴茱萸水煎液、挥发油组分、吴茱萸内酯组分均能降低幽门结扎大鼠胃溃疡的溃疡指数,与模型组比较有显著性差异（P〈0.05）;其余各化学拆分组分与模型组比较没有显著性差异（P〉0.05）。吴茱萸水煎液、挥发油组分、吴茱萸内酯组分能降低大鼠胃液胃蛋白酶活性,与模型组比较有显著性差异（P〈0.05）,对胃酸影响与模型组比较没有显著性差异（P〉0.05）。生物碱2组分可降低胃酸度,与模型组比较有显著性差异（P〈0.05）。结论：吴茱萸具有较明显抗胃溃疡作用,物质基础为挥发油、吴茱萸内酯、醇沉组分。     

断体地龙促进创伤愈合活性成分筛选研究

目的:从断体地龙提取液中筛选其促进创伤愈合的活性成分。方法:采用DEAE-Sepharose Fast Flow阴离子交换层析对断体地龙提取液进行分离纯化,通过CCK-8法测定不同洗脱液对NIH3T3细胞增殖的作用,筛选活性较强的组分。结果:离子交换层析梯度洗脱后得到5个洗脱峰。在一定浓度范围内,五种成分对NIH3T3细胞均有促进增殖作用,细胞增殖率随着蛋白浓度增大呈依赖上升趋势。当蛋白浓度为1.5μg/m L时,各组细胞增殖率均达到最大值,其中3号洗脱液作用的细胞增殖率最大。结论:断体地龙提取液经离子交换层析后得到的3号洗脱液促进NIH3T3细胞增殖作用最强,表明其可能含有促进创伤愈合的潜在活性成分,有待进一步研究。     

吴茱萸汤对化疗性异食癖恶心呕吐模型大鼠干预效果与作用机制的初步研究

目的研究不同剂量吴茱萸汤对顺铂诱导的大鼠化疗相关呕吐及肠道黏膜炎症的药效并初步探讨其作用机制。方法灌胃复方(吴茱萸汤)使用飞行时间高分辨质谱法对其活性成分进行定性。48只SD大鼠随机分为对照组、模型组、不同剂量吴茱萸汤组(5、10、20 mL/kg)以及阳性对照组(托烷司琼),每组8只。观察造模后1、3、5、7 d大鼠异嗜高岭土情况;液质联用方法定量检测各组大鼠血清中5-羟色胺(5-HT)的浓度;HE染色和免疫荧光观察大鼠结肠组织变化以及磷酸化组蛋白H2AX(γ-H2AX)、白细胞共同抗原(CD45)的表达。结果吴茱萸碱、吴茱萸次碱为吴茱萸汤的主要成分。治疗后,与模型组比较,吴茱萸汤高、中剂量组大鼠异嗜高岭土的量明显减少、血清5-HT浓度显著降低(P<0.01);病理形态学观察可见,吴茱萸汤高、中剂量组对大鼠结肠黏膜具有保护作用,并降低了γ-H2AX及CD45的表达(P<0.01)。结论吴茱萸汤能治疗顺铂诱导的大鼠化疗后呕吐,并能减轻其肠道炎症反应,其作用机制可能与降低血清中5-HT的浓度,抑制肠道γ-H2AX及CD45的表达有关。     

Gastroprotective effect of cardamom, Elettaria cardamomum Maton. fruits in rats

Cardamom, the fruits of Elettaria cardamomum Maton. (Zingiberaceae) commonly known as "Heel khurd" is used in Unani system of medicine to treat gastrointestinal disorders. A crude methanolic extract (TM), essential oil (EO), petroleum ether soluble (PS) and insoluble (PI) fractions of methanolic extract, were studied in rats at doses of 100-500, 12.5-50, 12.5-150 and 450 mg/kg, respectively for their ability to inhibit the gastric lesions induced by aspirin, ethanol and pylorous ligature. In addition their effects on wall mucus and gastric acid output were recorded. All fractions (TM, EO, PS, PI) significantly inhibited gastric lesions induced by ethanol and aspirin but not those induced by pylorus ligation. TM proved to be active reducing lesions by about 70% in the EtOH-induced ulcer model at 500 mg/kg. The PS fraction reduced the lesions by 50% at 50 and 100mg/kg (no dose response was observed) with similar effect than the PI fraction at 450 mg/kg. In the aspirin-induced gastric ulcer, the best gastroprotective effect was found in the PS fraction, which inhibited lesions by nearly 100% at 12.5mg/kg. In our experimental conditions, the PS extract at doses >or=12.5mg/kg proved to be more active than ranitidine at 50mg/kg.     

香附提取物的抗抑郁活性及其作用机制研究

目的:筛选香附抗抑郁活性部位并初步探讨其抗抑郁作用机制.方法:小鼠ig香附各提取物给药量均为10 g?kg -1,阳性对照药氟西汀(0.08 g?kg-1),连续给药15 d后进行测试,采用小鼠强迫游泳实验和小鼠尾悬挂实验对香附醇提物及其各极性部位进行抗抑郁活性筛选,继而采用反相高效液相色谱法测定大脑额叶皮质中单胺类神经递质含量变化,探讨香附抗抑郁作用机制.结果:香附醇提取物的乙酸乙酯萃取部位和正丁醇萃取部位与对照品氟西汀类似,均能显著缩短小鼠游泳和悬尾的不动时间,乙酸乙酯萃取部位活性强于正丁醇萃取部位.乙酸乙酯萃取部位和正丁醇萃取部位可明显升高小鼠大脑额叶皮质5-羟色胺(5-HT)和多巴胺(DA)含量(P＜0.01),去甲肾上腺素(NE)含量无明显改变.结论:香附醇提物乙酸乙酯萃取部位和正丁醇萃取部位对“行为绝望”动物模型有较明显的抗抑郁作用,其作用机制可能与调节脑内单胺类神经递质5-HT和DA的含量有关.     

Improving anticancer activities of Oplopanax horridus root bark extract by removing water‐soluble components

O. horridus is used as a folk medicine by natives in the Northern Pacific coast of North America. This experiment studied the antiproliferative effects of the extract of O. horridus root bark and its fractions chromatographed from Dianion HP20 resin column with water, 30, 50, 70 and 100% ethanol on human breast cancer MCF‐7 cells and non‐small cell lung cancer (NSCLC) cells. The role of O. horridus in the cell cycle and apoptosis of MCF‐7 cells was also investigated. The results showed that the 70% and 100% ethanol fractions demonstrated more potent antiproliferative effects than the total extract on both cell lines. The antiproliferative effects may result from the enrichment of active constituents detected by high performance liquid chromatography (HPLC). The IC₅₀ of the total extract, 50, 70, and 100% ethanol fractions for antiproliferation on MCF‐7 cells were 248.4, 123.1, 44.0, and 31.5 μg/mL, respectively, and on NSCLC cells were 125.3, 271.1, 17.6, and 23.2 μg/mL, respectively. On the other hand, the water and 30% ethanol fractions significantly promoted cell proliferation on MCF‐7 cells at concentrations > 100 μg/mL, suggesting that the hydrophilic fractions should be removed from the extract when used for cancer chemoprevention in order to achieve desirable activities. The effects of the total extract on cell cycle and apoptosis were similar to that of the 100% ethanol fraction because of the similarity of their chemical composition. At higher concentrations, the apoptotic effects of the 70% ethanol fraction are more significant. Data from this study suggested that the 70% and 100% ethanol fractions are active antiproliferative fractions and that induction of apoptosis is the mechanism involved in the antiproliferative effect observed. Copyright © 2010 John Wiley & Sons, Ltd.     

Mechanism of action of the aqueous seed extract of Mucuna pruriens on the guinea-pig ileum

The hot water extract (HWE) of the seed of Mucuna pruriens dose-dependently contracted the guinea-pig ileum. The ED₅₀ and pD₂ values for the HWE was lower than those of ACh and histamine. Cyproheptadine and promethazine (10 ng/mL) significantly antagonized the effects of histamine, 5-hydroxytryptamine (5-HT) and HWE. Atropine blocked the effect of ACh and partially blocked the HWE. The calcium channel blockers nifedipine and verapamil both blocked the effects of all the agonists including HWE. These results suggest that the HWE contains potent histamine receptor stimulants or principles as it was blocked by low doses of H₁ receptor blockers. It appears that stimulation of the receptors leads to influx of calcium since the effect was also blocked by nifedipine and verapamil. It is likely that it also stimulates muscarinic receptors. © 1997 John Wiley & Sons, Ltd.     

Antidepressant-like effect of ethanol extract from Zuojin Pill,containing two herbal drugs of Rhizoma Coptidis and Fructus Evodiae,is explained by modulating the monoaminergic neurotransmitter system in mice

Ethnopharmacological relevance

Zuojin Pill (ZJP), a traditional Chinese medicinal decoction, contains two herbal drugs: Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in the ratio of 6:1 (w/w). Previous pharmacological studies have shown that two herbs in ZJP have the antagonistic effects on catecholamine secretion in bovine adrenal medullary cells. Furthermore, the alkaloids from the two herbs in ZJP may provide a protective effect for depression in individuals with a low expressing 5-HTT allele by increasing receptor concentration in serotonergic neurons. However, antidepressant effect has not been reported before and has not been fully clarified.

Aim of the study

The present study aimed to investigate the antidepressant potential of ethanol extract from ZJP and its monoaminergic mechanism in mice.

Materials and methods

Seven alkaloids were determined from the ethanol extract of ZJP using High Performance Liquid Chromatography (HPLC) with the gradient mobile phase. The ethanol extract from ZJP was used to evaluate the antidepressant potential in mice. Mouse models of depression including the tail suspension test (TST) and the forced swim test (FST) were used to evaluate the effects of the ethanol extract from ZJP. A possible mechanism was explored in the tests of antagonism of reserpine-induced ptosis and hypothermia, and 5-HTP induced head twitch response in mice. The contents of monoamine neurotransmitters including norepinephrine (NE), serotonin (5-hydroxytryptamine or 5-HT) in hippocampus of mice and NE, 5-HT, dopamine (DA) in striatum of mice were determined by HPLC system with Electrochemical Detector (ECD).

Results

The results showed that intragastric administration of the ethanol extract from ZJP (5, 10, 20 mg/kg) or fluoxetine (7.5 mg/kg) significantly reduced the duration of immobility in TST and FST. However, the effect was not dose-dependent. Ethanol extract from ZJP (5, 10, 20 mg/kg) also increased the accumulative number of the 5-HTP-induced head twitch response in mice. The mice were treated with the ethanol extract from ZJP (5, 10, 20 mg/kg) or fluoxetine (7.5 mg/kg), which could antagonize reserpine-induced ptosis and hypothermia, moreover, both of them could elevate the contents of NE, 5-HT in hippocampus as well as NE, 5-HT, DA in striatum significantly.

Conclusion

These results indicate that the ethanol extract from ZJP produced antidepressant-like effect and the possible mechanism, at least in part, is via the central monoaminergic neurotransmitter system and 5-HT plays a major role.     

连翘对豚鼠离体回肠运动的影响

目的:观察连翘对豚鼠离体肠管运动的影响,以期探讨其止呕作用的机制。方法:以呕吐相关受体激动剂为工具药,利用离体恒温浴槽,观察连翘对豚鼠离体回肠收缩的影响。结果:连翘能够抑制离体肠管的自发活动,表现为收缩张力降低,并呈剂量依赖性关系。乙酰胆碱(acetylcholine,Ach)、组织胺(histamine,His)、五羟色胺(5-hydroxytryptamine,5-HT)能够兴奋肠管,使张力升高、振幅变大,连翘高(10 g·L-1)、中(5 g·L-1)、低(2 g·L-1)剂量均能抑制以上3种工具药所致肠管收缩,降低其收缩张力和振幅,但对频率无明显影响。多巴胺(dopamine,DA)能够抑制肠管收缩,表现为张力降低、振幅变小,连翘高剂量和中剂量能够拮抗DA的肠管松弛作用,使张力升高、振幅变大;连翘低剂量能够进一步使张力降低,但使振幅增大。结论:连翘可以抑制豚鼠回肠运动,其机制可能是通过阻断肠平滑肌上的M受体、H1受体、5-HT受体和D2受体,也可能是对肠管的直接抑制作用,其止呕机制尚待进一步深入研究。     

云木香丙酮提取物对大鼠实验性胃溃疡模型的影响

目的:观察云木香丙酮提取物对两种大鼠胃溃疡模型的影响,并初步探讨其作用机制.方法:采用乙醇法及冷水束缚法诱发大鼠急性胃溃疡模型,以木香丙酮提取物灌胃给药,观察其对两种模型的作用,并观察其对正常小鼠胃排空及肠推进影响,初步探讨其作用机制.结果:云木香丙酮提取物能显著对抗乙醇和冷水束缚法所致的大鼠胃溃疡,对小鼠胃排空及肠推进无明显影响.结论:云木香丙酮提取物对两种模型具有显著的保护作用,其作用机制不在于促进胃排空和肠推进.     

Relaxant effect of essential oil and hydro-alcoholic extract of Pycnocycla spinosa Decne. exBoiss. on ileum contractions

Pycnocycla spinosa is an essential oil from a wild plant growing in central Iran. However, so far its pharmacological effects have not been studied. The aim of this study was to look for relaxant effects of the essential oil and hydro-alcoholic extract of P. spinosa on rat isolated ileum contractions induced by KCl and acetylcholine (ACh). P. spinosa essential oil (PSEO) and the hydro-alcoholic extract inhibited the response to 80 mM KCl in a concentration-dependent manner and attenuated the maximum attainable response of ACh concentration-response curve. Furthermore, in caster oil induced diarrhoea, the hydro-alcoholic extract had a dose-dependent anti-diarrhoeal effect. This study showed that P. spinosa essential oil and its hydro-alcoholic extract act as a relaxant of rat isolated ileum. As the inhibition of contractile over-activity of the ileum is the basis for the treatment of gastro-intestinal disorders such as diarrhoea, P. spinosa may have clinical bene fi ts for treatment of this condition.     

Inhibition of [3H]-LSD binding to 5-HT7 receptors by flavonoids from Scutellaria lateriflora

The hot water and 70% ethanol extracts of dried mad-dog skullcap (Scutellaria lateriflora) both bound to the 5-HT(7) receptor, with 87.2 +/- 6.2% and 56.7 +/- 1.3% inhibition of [(3)H]-LSD binding to the receptor at 100 microg/mL, respectively. The on-line analysis of a 70% ethanol extract by HPLC-UV/MS resulted in the identification of five flavones (1-5). Fractionation of the ethanol extract resulted in the isolation of three flavone-glucuronides (6-8) and a flavanone-glucuronide (9), including one new compound, lateriflorin (5,6,-dihydroxy-7-glucuronyloxy-2'-methoxyflavone) (8). The structure of 8 was determined by NMR ((1)H NMR, (13)C NMR, and NOESY experiments) and MS analysis. From the results obtained in the testing of the pure compounds, it is evident that the activity on the 5-HT(7) receptor is at least partly due to the presence of flavonoids. Scutellarin and ikonnikoside I showed the highest inhibition of [(3)H]-LSD binding with IC(50) values of 63.4 and 135.1 microM, respectively.     

Mechanisms of relaxant action of a crude hexane extract of Gnaphalium liebmannii in guinea pig tracheal smooth muscle

We investigated the mechanisms of action of Gnaphalium liebmannii which is used as a folk medicine in México for treating various respiratory diseases such as gripe, fever, asthma, cough, cold, bronchitis, expectorating, and bronchial affections. The tension changes of guinea pig tracheal segments were isometrically recorder on a polygraph. Hexane extract of Gnaphalium liebmannii was the most active relaxant extract (IC(30)=54.23+/-19.79 microg/mL with 99.5+/-3.2 % of relaxation), followed by dichloromethane extract (IC(30)=120.22+/-5.27 microg/mL) and methanol extract (IC(30)=190.25+/-30.02 microg/mL). Hexane extract produced a parallel rightward shift of the concentration-response curve of carbachol in a competitive manner (pA(2)=-2.4), but did not modify the concentration-response curves for histamine. The relaxant effect of hexane extract of Gnaphalium liebmannii was unaffected by the presence of propranolol (3x10(-6)M) or glibenclamide (10 microM). However hexane extract produced a leftward shifts of the concentration-response curve of forskolin (10(-8) to 10(-3)M), nitroprusside (10(-10) to 10(-6)M), isoproterenol (3x10(-10) to 3x10(-5)M) and aminophylline (10(-11) to 10(-2)M). The above results suggest that Gnaphalium liebmannii induce relaxation of the tracheal muscle, probably via phosphodiesterase inhibition. The bronchodilator effect of Gnaphalium liebmannii might explain in part their traditional use as anti-asthmatic remedy.