疏肝健脾方对腹泻型肠易澉综合征大鼠血浆及结肠组织5-HT、SP、VIP的影响

[目的]观察疏肝健脾方对腹泻型肠易激综合征大鼠血浆及结肠组织5-羟色胺（5-HT）、P物质（SP）和血管活性肠肽（VIP）的影响。[方法]将60只SD大鼠按随机数字表法随机分为正常组、模型组、得舒特组、疏肝健脾方低、中、高剂量组,使用乙酸灌肠加束缚的方法建立腹泻型肠易激综合征（D—IBS）大鼠模型,应用免疫组化法检测5-HT、SP及VIP。[结果]疏肝健脾方可以明显降低大鼠的粪便含水量（P〈0．05）;疏肝健脾方中、高剂量组腹部撤退反射（AWR）评分在不同扩张容量下均较模型组明显降低（P〈0．05）;疏肝健脾方可以降低大鼠血浆中5-HT和结肠组织中sP的含量,而血浆中SP、VIP及结肠组织中VIP含量无显著变化。[结论]疏肝健脾方可以改善大鼠的腹泻及内脏的高敏感性,并对5-HT及SP有调节作用,提示疏肝健脾方可以有效治疗D—IBS,并与调节胃肠激素有关。     

Partial agonistic effect of yokukansan on human recombinant serotonin 1A receptors expressed in the membranes of Chinese hamster ovary cells

Ethnopharmacological relevance

Yokukansan (YKS) is a traditional Japanese medicine consisted of seven medicinal herbs and has been used for treatment of neurosis, insomnia, and behavioral and psychological symptoms of dementia (BPSD) in Japan.

Aim of the study

The aim of the present study is to clarify the intrinsic activity of YKS on serotonin (5-HT)1A and 5-HT2A receptors and also to determine the constituent herbs which are responsible for the effect of YKS.

Materials and methods

The dry powdered extracts of YKS, seven constituent herbs, and YKS-analogues which were produced by eliminating one of the constituent herbs from YKS in the manufacturing process, were used for the evaluation. Competitive binding assays for 5-HT receptors and [³⁵S]GTPγS binding assays for the evaluation of agonistic/antagonistic activity were performed using Chinese hamster ovary cell membranes stably expressing human recombinant 5-HT1A or 5-HT2A receptors.

Results

YKS (6.25–400 μg/ml) concentration-dependently inhibited the binding of [³H]8-OH-DPAT to 5-HT1A receptors. The IC₅₀ value was estimated to be 61.2 μg/ml. In contrast, YKS failed to inhibit the binding of [³H]ketanserin to 5-HT2A receptors. Only Uncaria hook (3.13–50 μg/ml), of the seven constituent herbal extracts, inhibited the [³H]8-OH-DPAT binding to 5-HT1A receptors in a concentration-dependent manner, and the IC₅₀ value was estimated to be 7.42 μg/ml. The extracts of YKS or Uncaria hook increased [³⁵S]GTPγS binding to 5-HT1A receptors to approximately 50% of that of a full agonist, 5-HT. Both the competitive binding and [³⁵S]GTPγS binding of YKS to 5-HT1A receptors were remarkably attenuated by eliminating Uncaria hook from YKS, but it was almost unchanged when one of the other constituent herbs was eliminated from YKS.

Conclusion

These results suggest that YKS has a partial agonistic effect on 5-HT1A receptors, which is mainly attributed to Uncaria hook.     

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.     

Alkaloids from Eschscholzia californica and their capacity to inhibit binding of [3H]8-Hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A receptors in Vitro

A 70% ethanol extract of California poppy (Eschscholzia californica) was able to bind to 5-HT(1A) and 5-HT(7) receptors at 100 mug/mL. The subsequent isolation procedure yielded the known alkaloids californidine (1), escholtzine (2), N-methyllaurotetanine (3), caryachine (4), and O-methylcaryachine (5), along with a new pavine alkaloid, 6S,12S-neocaryachine-7-O-methyl ether N-metho salt (7). The structure of 7 was determined by spectroscopic data interpretation, while the absolute stereochemistry was determined by means of circular dichroism. From the results obtained from the radioligand-binding assay of the pure compounds, including the commercially available protopine (6), it was evident that the activity on the 5-HT(1A) receptor was at least partly due to the presence of the aporphine alkaloid 3, which showed the highest inhibition of [(3)H]8-hydroxy-2-(di-N-propylamino)tetralin ([(3)H]8-OH-DPAT) binding with an EC(50) value of 155 nM and a K(i) of 85 nM.     

An aqueous extract of Poncirus fructus activates the prokinetic activity of 5-HT receptor subtype 4 without hERG interaction

Aim of the study

Poncirus fructus (PF) - also known as the dried, immature fruit of Poncirus trifoliata (L.) Raf. (Rutaceae) - is a natural substance that has long been used for various gastrointestinal disorders in eastern Asia. An aqueous extract of PF (PF-W) has particularly potent gastroprokinetic effects, but its molecular mechanism was not well understood. Identification of the underlying prokinetic mechanism of PF-W was pursued in the present study.

Materials and methods

Changes in in vitro cAMP levels and in vivo intestinal transit rate (ITR) caused by PF-W were measured after pretreatment with GR125487, an antagonist for serotonin receptor subtype 4 (5-HT4R). An [³H] astemizole binding assay and electrophysiology experiments were performed to determine if PF-W has any interaction with the human ether-à-go-go related gene (hERG) potassium channel.

Results

PF-W induced an increase in intracellular cAMP in 5-HT4R-expressing HEK293T cells, indicating that PF-W does activate 5-HT4R. Moreover, pretreatment with GR125487 successfully blocked the increase, suggesting that the response was 5-HT4R-specific. More importantly, pretreatment of GR125487 in rats inhibited the elevation of ITR by PF-W, indicating that the prokinetic effect of PF-W was indeed exerted via 5-HT4R. On the other hand, both [³H]-astemizole binding assay and electrophysiological experiments revealed that PF-W did not interfere at all with the hERG channel.

Conclusion

It was found that PF-W exerts its prokinetic activity through a 5-HT4R-mediated pathway, with no interaction with hERG channels. Therefore, PF-W is a good candidate that might be developed as a prokinetic agent with fewer expected cardiac side effects.     

针刺对5-HT致痒大鼠IgE与5-HT2A受体的影响

[目的]观察针刺对5-HT致痒大鼠的止痒效果,探讨针刺对5-HT致痒大鼠的行为学指标,以及血清中IgE与皮肤中5-HT2A受体的影响。[方法]64只大鼠随机分为8组,分别为空白对照组、模型组、阳性药物组、常规治疗组、针刺治疗1组、针刺治疗2组、中药治疗1组、中药治疗2组,每组8只。空白对照组和模型对照组予生理盐水灌胃,阳性药物组予喂饲酮舍林,常规治疗组予喂饲开瑞坦,针刺治疗1组针刺委中等穴位,针刺治疗2组针刺血海等穴位,中药治疗1组予当归、生地等中药灌胃,中药治疗2组予乌梅等中药灌胃。取空白对照组大鼠于其颈背部皮内注射10μL0.9%生理盐水,取其余各组大鼠于其颈背部皮内（肩胛连线中点上方5mm处）注射10μL2%5-HT（94mmol/L）溶液。建立瘙痒模型后,观察大鼠搔抓次数,并测定大鼠血清中IgE和皮肤中5-HT2A受体含量。[结果]模型组大鼠血清IgE升高,皮肤内5-HT2A受体升高,搔抓次数增加;两组针刺治疗组大鼠血清IgE降低,皮肤内5-HT2A受体降低,搔抓次数减少。[结论]针刺治疗可降低5-HT致痒大鼠血清中IgE和皮肤内5-HT2A受体的浓度,对其搔抓症状有明显的抑制作用。     

针刺对5-HT致痒大鼠IgE与5-HT2A受体的影响

[目的]观察针刺对5-HT致痒大鼠的止痒效果,探讨针刺对5-HT致痒大鼠的行为学指标,以及血清中IgE与皮肤中5-HT2A受体的影响。[方法]64只大鼠随机分为8组,分别为空白对照组、模型组、阳性药物组、常规治疗组、针刺治疗1组、针刺治疗2组、中药治疗1组、中药治疗2组,每组8只。空白对照组和模型对照组予生理盐水灌胃,阳性药物组予喂饲酮舍林,常规治疗组予喂饲开瑞坦,针刺治疗1组针刺委中等穴位,针刺治疗2组针刺血海等穴位,中药治疗1组予当归、生地等中药灌胃,中药治疗2组予乌梅等中药灌胃。取空白对照组大鼠于其颈背部皮内注射10μL0.9%生理盐水,取其余各组大鼠于其颈背部皮内(肩胛连线中点上方5mm处)注射10μL2%5-HT(94mmol/L)溶液。建立瘙痒模型后,观察大鼠搔抓次数,并测定大鼠血清中IgE和皮肤中5-HT2A受体含量。[结果]模型组大鼠血清IgE升高,皮肤内5-HT2A受体升高,搔抓次数增加;两组针刺治疗组大鼠血清IgE降低,皮肤内5-HT2A受体降低,搔抓次数减少。[结论]针刺治疗可降低5-HT致痒大鼠血清中IgE和皮肤内5-HT2A受体的浓度,对其搔抓症状有明显的抑制作用。     

Mode of action of peppermint oil and (-)-menthol with respect to 5-HT3 receptor subtypes: binding studies, cation uptake by receptor channels and contraction of isolated rat ileum

Peppermint oil (Mentha × piperita L. (Lamiaceae) has been shown to exert potent antiemetic properties, but its mode of action has not yet been elucidated. Among its active constituents (-)-menthol is the most important. Three different in vitro models were used to investigate the effects on 5-HT(3) receptors (serotonin receptor subtype): [(14)C]guanidinium influx into N1E-115 cells which express 5-HT(3) receptors, isotonic contractions of the isolated rat ileum and equilibrium competition binding studies using a radioactively labelled 5-HT(3) receptor antagonist ([(3)H]GR65630) (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone). Both peppermint oil and (-)-menthol inhibited [(14)C]guanidinium influx through 5-HT(3) receptor channels as well as contractions of the ileum induced by serotonin. Neither the peppermint oil nor (-)-menthol, however, was able to displace [(3)H]GR65630 from 5-HT(3) binding sites. It may be concluded that peppermint oil and (-)-menthol exert their antiemetic effect at least partly by acting on the 5-HT(3) receptor ion-channel complex, probably by binding to a modulatory site distinct from the serotonin binding site.     

泻肝安神法对睡眠剥夺大鼠单胺类神经递质影响的研究

[目的]探讨泻肝安神法对睡眠剥夺大鼠脑干及海马脑区单胺类神经递质含量的干预效应。[方法]采用水平台睡眠剥夺法造模后,给予泻肝安神法干预7 d后取材,高效液相色谱法检测脑干及海马脑区7种单胺类神经递质的含量。[结果]大鼠剥夺睡眠后脑干单胺类神经递质5-羟吲哚乙酸(5-HIAA)、5-羟色胺(5-HT)明显下降,多马胺(DA)、去甲肾上腺素(NE)、3-甲氧基4-羟基苯乙酸(HVA)明显升高,二羟苯乙酸(DOPAC)无明显变化。而在海马区域各单胺类神经递质含量变化不显著。采取泻肝安神法治疗后大鼠脑干5-HT、5-HIAA含量显著升高,DA含量明显下降;而在双侧海马5-HT、5-HIAA、DA、HVA升高,NE下降。采用地西泮片治疗后大鼠在海马区的单胺类神经递质变化与中药组结果一致,但在脑干仅有5-HIAA升高,而5-HT、DA则没有明显变化。[结论]泻肝安神法可调节睡眠剥夺大鼠的单胺类神经递质,且影响靶点要多于地西泮片,机制可能与综合的调节单胺类神经递质水平,纠正其紊乱相关。     

UPLC法测定人参流动浸膏中8种人参皂苷类成分

[目的]建立同时测定人参流动浸膏中8种人参皂苷类成分含量的超高效液相色谱法(UPLC)方法。[方法]采用Waters AcqutityUPLC色谱系统,Acqutity UPLC誖BEH C18(1.7μm,2.1 mm×50 mm)色谱柱,流动相为乙腈-水,梯度洗脱,流速0.6 mL/min,柱温40℃,检测波长203nm。[结果]人参皂苷Rg1、Re、Rf、Rb1、Rc、Rb2、Rb3和Rd分别在0.009 7~0.291 0μg,0.008 5~0.255 0μg,0.0075~0.300 0μg,0.010 4~0.416 0μg,0.010 7~0.428 0μg,0.007 4~0.296 0μg,0.004 2~0.168 0μg和0.009 1~0.364 0μg范围内成良好的线性关系,平均回收率分别为101.4%、101.1%、100.1%、99.8%、99.3%、98.8%、98.8%和100.5%。[结论]方法快速、准确、重复性好,可为人参流动浸膏的质量控制提供快速准确的检测方法。     

抗郁汤对PSD小鼠自发性行为和外周血清5-羟色胺(5-HT)影响

[目的]观察抗郁汤对PSD小鼠自发性行为和血清5-羟色胺(5-HT)影响。[方法]将60只小鼠按体重随机分组。采用阻断单侧颈总动脉制备脑缺血再灌注模型。使用不同剂量抗郁汤进行干预,通过悬尾、强迫游泳实验,实验第6天测定模型鼠自发性行为、血清5-羟色胺(5-HT)指标。[结果]小鼠悬尾累计静止时间,模型组比空白对照组长(P<0.05),高剂量组明显低于模型组(P<0.01),中剂量组高于阳性对照组(P<0.05);强迫游泳累计静止时间模型组比空白对照组长(P<0.05),高剂量组、中剂量组及阳性对照组均低于模型组(P<0.05);血清5-HT含量模型组低于对照组(P<0.01),高剂量组、中剂量组及阳性对照组均高于模型组(P<0.05)。[结论]抗郁汤干预可使PSD小鼠血清中5-HT水平明显增高,增强自发性行为。     

吴茱萸汤醇提各组分止呕活性的研究

目的 :对吴茱萸汤醇提各组分止呕活性的研究和机制初步探讨。方法 :采用硫酸铜诱导家鸽呕吐实验 ,小鼠胃排空实验 ,ACh和 5-HT作用的离体大鼠胃条实验来确定其中具有止呕活性的组分 ,并观察有效组分对ACh ,5-HT ,组胺累积浓度 效应曲线的影响。结果 :50%醇洗脱液和 70%醇洗脱液有十分显著性的止呕效应 ,且副作用较小 ,对ACh ,5-HT ,组胺累积浓度 效应曲线均有一定的作用。结论 :50%醇洗脱液和 70%醇洗脱液含有的止呕活性成分较多 ,50%和 70%醇可以从吴茱萸汤中提取较多止呕活性成分 ,止呕作用可能与拮抗ACh ,5-HT ,组胺受体有关。     

5-Hydroxytryptamine2A receptor binding activity of compounds from Litsea sessilis

A 96-well microplate filtration based 5-HT(2A) receptor-radioligand binding assay was optimized and adopted to carry out a bioassay-guided fractionation of the methanol extract of the leaves of Litsea sessilis. This purification led to the isolation of two compounds identified as (+)-boldine (1) and (+)-dehydrovomifoliol (2). (+)-Boldine binds to 5-HT(2A) receptors at high concentrations with a K(i) value of 2.16 microm. However, (+)-dehydrovomifoliol showed minimal competitive inhibition on the binding of [(3)H]ketanserin to the same receptor with a K(i) value of 2.06 mm. These results suggest that (+)-boldine influences the activity of 5-HT(2A) receptors through competitive binding as an agonist or antagonist.     

紫菀正丁醇萃取液化学成分研究

目的：研究紫菀正丁醇萃取液的化学成分。方法：利用大孔树脂、硅胶柱层析以及制备液相分离化合物,并利用现代波谱技术进行结构鉴定。结果：从中药紫菀中正丁醇萃取部位分得9个化合物,其中紫菀皂苷类4个,分别为：3-O-[O-α-D-吡喃阿拉伯糖-（1→6）-β-D-吡喃葡萄糖基]-2β,3β,16α-三羟基齐墩果烷-12-烯-28-酸28-[O-β-D-吡喃木糖基-（1→3）-O-α-L-吡喃阿拉伯糖基-（1→4）-[O-β-D-呋喃芹菜糖基-（1→3）]-O-α-L-吡喃鼠李糖基-（1→2）-β-D-吡喃木糖基]酯（astersaponin A,1）、3-O-[O-α-L-吡喃阿拉伯糖基-（1→6）-β-D-吡喃葡萄糖基]-2β,3β,16α-三羟基齐墩果烷-12-烯-28酸8-[O-β-D-吡喃木糖基-（1→3）-O-α-L-吡喃阿拉伯糖基-（1→4）-[O-β-D-呋喃芹菜糖基-（1→3）-O-α-L-吡喃鼠李糖基-（1→2）-O-α-L-吡喃鼠李糖基-（1→3）]-β-D-吡喃木糖基]酯（astersaponin C,2）、3-O-[O-α-L-吡喃阿拉伯糖基-（1→6）-β-D-吡喃葡萄糖基]-2β,3β,16α-三羟基齐墩果烷-12-烯-28-酸28-[O-β-D-吡喃木糖基-（1→3）-O-α-L-吡喃阿拉伯糖基-（1→4）-O-α-L-吡喃鼠李糖基-（1→2）-β-D-吡喃木糖基]酯（astersaponin E,3）和3-O-[O-α-D-吡喃阿拉伯糖-（1→6）-β-D-吡喃葡萄糖基]-2β,3β,16α-三羟基齐墩果烷-12-烯-28-酸（4）,以及shionosides A（5）、epifriedelinol（6）、astin C（7）、二十四烷酸（8）和棕榈酸（9）。结论：化合物4为新的天然产物。     

芎麻汤不同提取物对小鼠偏头痛模型的影响

目的:观察芎麻汤不同提取物治疗偏头痛的药理作用。方法:采用小鼠皮下注射1 mg.kg-1利血平致小鼠偏头痛模型、醋酸致小鼠扭体模型,昆明小鼠随机分为阿米替林组(0.033 g.kg-1)、芎麻汤水提液组(1.4,5.6 g.kg-1)、芎麻汤醇提组(1.4,5.6 g.kg-1)、芎麻汤挥发油组(1.4,5.6 g.kg-1),连续给药7 d,观察芎麻汤水提液,挥发油、醇提液对偏头痛模型小鼠血清5-羟色胺(5-HT)含量及镇痛作用的影响。结果:芎麻汤水提液(5.6 g.kg-1)能明显升高利血平化低5-HT小鼠模型血清中5-HT的含量(P<0.01),芎麻汤挥发油(1.4,5.6 g.kg-1)能明显延长冰醋酸致小鼠扭体潜伏期及减少扭体次数。结论:芎麻汤水提液对偏头痛小鼠模型有一定的作用,芎麻汤挥发油具有一定的镇痛作用。     

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.     

Phelligridins C-F: cytotoxic pyrano[4,3-c][2]benzopyran-1,6-dione and furo[3,2-c]pyran-4-one derivatives from the fungus Phellinus igniarius

Three unique pyrano[4,3-c][2]benzopyran-1,6-dione derivatives and a new furo[3,2-c]pyran-4-one, named phelligridins C-F (2-5), together with hispolon (8), (E)-4-(3,4-dihydroxyphenyl)but-3-en-2-one (9), 4-hydroxybenzaldehyde, protocatechualdehyde, syringic acid, protocatechuic acid, caffeic acid, isoergosterone, and octadecyl ferulate were isolated and identified from the ethanolic extract of Phellinus igniarius. Their structures were determined by spectroscopic methods including IR, MS, and 1D and 2D NMR experiments. The structures of the new compounds were characterized as 3-(4-hydroxystyryl)-8,9-dihydroxypyrano[4,3-c]isochromene-4-one (2), 3-(3,4-hydroxystyryl)-8,9-dihydroxypyrano[4,3-c]isochromene-4-one (3), 8,9-dihydroxy-3-[5',6'-dihydroxy-5' '-methyl-3' '-oxo-spiro[fural-2' '(3' 'H),1'-indene]-2'-yl]-1H,6H-pyrano[4,3-c][2]benzopyran-1,6-dione (4), and (3Z)-3-(3,4-dihydroxybenzylidene)-6-(3,4-dihydroxystyryl)-2,3-dihydro-2-methoxy-2-(2-oxo-propyl)furo[3,2-c]pyran-4-one (5), respectively. Some compounds including 2 and 3 showed in vitro selective cytotoxicity against a human lung cancer cell line (A549) and a liver cancer cell line (Bel7402). Possible biogenetic sequences to the formation of 1-9 are postulated.     

Brain neurotransmitter receptor binding and nootropic studies on Indian Hypericum perforatum Linn

The high affinity binding sites for serotonin and benzodiazepine in the frontal cortex, for dopamine in the striatum and muscarinic cholinergic receptors in the hippocampus were investigated in the brains of Charles Foster rats treated for 3 days. Transfer latency on elevated plus maze (TL), passive and active avoidance behaviour (PA and AA) and electroconvulsive shock (ECS) induced amnesia were also studied. Pilot studies indicated that single dose administration of Indian Hypericum perforatum (IHp) had little or no acute behavioural effects and hence the extract of IHp was administered orally at two dose levels (100 and 200 mg/kg, p.o.) once daily for 3 consecutive days, while piracetam (500 mg/kg, i.p.), a clinically used nootropic agent, was administered acutely to rats as the standard nootropic agent. Control rats were treated with an equal volume of vehicle (0.3% carboxymethyl cellulose). The results indicate that IHp treatment caused a significant decrease in the binding of [3H] spiroperone (DA-D2 receptor) to the striatum and an increase in the binding of [3H] ketanserin (5-HT2A receptor) and [3H] flunitrazepam (BDZ receptor) to the frontal cortex in rats. Preliminary pharmacological studies with IHp extract indicate the presence of two major behavioural actions, namely, antidepressant and anxiolytic. The present findings tend to elucidate the mechanism of earlier observations, the downregulation of the dopamine D2 receptor being consonant with anxiolytic and the upregulation of 5-HT2A and BDZ receptors being consonant with antidepressant activity. Piracetam when given alone, shortened the TL on days 1, 2 and 9 day and also antagonized the amnesic effects of ECS on the TL significantly, whereas IHp antagonized the amnesia produced by ECS. IHp had no significant effect per se on the retention of the PA in rats but produced a significant reversal of ECS induced PA retention deficit. Piracetam showed a significant facilitatory effect per se on PA retention and also reversed the ECS induced impaired PA retention. In the AA test, piracetam facilitated the acquisition and retention of AA in rats but IHp had no effect per se. Both the doses of IHp and piracetam significantly attenuated the ECS induced impaired retention of AA. These results indicate a possible nootropic action of IHp in amnesic animals, which was comparable qualitatively to piracetam.     

小柴胡汤联合5-氟尿嘧啶治疗Hca—f肝癌小鼠实验研究

[目的]研究中医经典方剂小柴胡汤（以下简称xcht）联合化疗药物5-氟尿嘧啶（以下简称5-Fu）对小鼠Hca—f肝癌的抑瘤作用及其免疫作用机制。[方法]无菌条件下抽取Hca—f腹水为瘤源,用生理盐水稀释为4x10。个瘤细胞／mL,每鼠予0．2mL于其右侧腋窝皮下接种。24h后随机分成单纯肿瘤组、xcht组、5-Fu组、xcht＋5-Fu组,给药10天后,处死小鼠,剥离并称量瘤重,计算抑瘤率;光镜下观察肿瘤细胞的形态;电镜下观察凋亡小体。[结果]xcht能抑制Hca—f小鼠体内肿瘤的生长,并能提高5－Fu对Hca—f肝癌小鼠的疗效。[结论]小柴胡汤与5－Fu联合用药对小鼠体内Hca—f肝癌细胞的生长有较好抑制作用,且疗效优于单独用药。     

Neuromuscular effects and acute toxicity of an ethyl acetate extract of Spigelia anthelmia Linn

An ethyl acetate extract of Spigelia anthelmia (EASa), with validated anthelmintic activity, was evaluated for its acute toxicity and general effects in albino Swiss mice and for neuromuscular relaxant activity in the frog sciatic-gastrocnemius and rectus abdominis preparation. The extract induced a dose-related myotonia and muscular paralysis of rapid onset at higher doses. The calculated LD50 after oral and intraperitoneal administration was 345.9 [241.4-484.7] mg/kg and 60.8 [47.4-80] mg/kg, respectively. In broilers, intramuscular injection of EASa-induced spastic paralysis qualitatively similar to that obtained after succinylcholine administration and contrasting to the flaccid paralysis induced by D-tubocurarine. The contraction elicited by direct stimulation of the gastrocnemius was blocked by EASa by 54.3+/-4.7% (IC50 = 21.4 [11.2-35.8] microg/ml) and the twitches evoked by stimulation of the sciatic nerve were blocked by 69.1+/-7.4% (IC50 = 17.9 [4.5-34.23] microg/ml). EASa also blocked acetylcholine-induced contractions in the frog rectus abdominis by 58.6+/-7.4% (IC50 = 7.4 [1.7-15.28] microg/ml) but did not decrease tonic contractions induced by a high-potassium Ringer solution. In summary, the ethyl acetate extract of Spigelia anthelmia induces tonic paralysis in vivo, and decreases amplitudes of twitches and increases tonus of skeletal muscle in vitro.