瑞香狼毒抗癫痫活性部位筛选及活性部位中总黄酮含量测定

目的探索瑞香狼毒抗癫痫活性部位、活性部位中总黄酮含量测定方法及总黄酮含量与抗癫痫活性之间的关系。方法采用乙醇提取和不同溶剂萃取等手段,通过惊厥实验模型对瑞香狼毒各提取部位的活性筛选,确定其抗癫痫活性部位;采用紫外分光光度法对活性部位中总黄酮进行了含量测定。结果初步确定乙醚提取部位与丙酮提取部位为其抗癫痫活性部位,乙醚提取部位表现出较强的抗癫痫活性和较高的死亡率,丙酮提取部位显示了更强的综合治疗效果;乙醚活性部位中总黄酮含量为8.51%,丙酮活性部位中总黄酮含量为5.07%。结论紫外分光光度法测定其活性部位中总黄酮含量,准确性高、重现性好、简便易行;初步推断其活性部位中总黄酮含量越高,其抗癫痫活性作用也可能越强。     

不同极性溶媒瑞香狼毒提取物的抗肿瘤活性比较

目的：通过比较不同极性溶媒瑞香狼毒提取物的体外抗肿瘤活性，确定瑞香狼毒抗肿瘤活性成分所在的极性区间。方法：采用索氏回流提取法，依次用石油醚、乙酸乙酯、丙酮和乙醇对狼毒进行回流提取，并用不同浓度的各溶剂提取物分别处理Eca109、K562、HepG_2细胞株，通过MTT检测法，比较各溶媒提取物对肿瘤细胞的抑制活性。结果：石油醚提取物和乙酸乙酯提取物对体外培养肿瘤细胞表现出较强的抑制作用，在测定浓度范围内呈现出良好剂量依赖性，石油醚提取物最大抑制率分别为78％(Eca-109)、93％(K562)、95％(HepG_2)，乙酸乙酯提取物最大抑制率分别为53％(Eca-109)、91％(K562)、87％(HepG_2)；而丙酮和乙醇提取部位在测定浓度范围内则显示出很弱的抑制作用；在各提取物中石油醚提取物的体外抗肿瘤作用最强。结论：石油醚提取成分是瑞香狼毒中体外抗肿瘤活性最强的部位。     

瑞香狼毒成分抗惊厥作用的初步研究

目的：应用不同溶剂对天然植物瑞香狼毒进行提取，并对不同提取物进行抗惊厥活性的初步实验，探索其治疗癫痫的有效化学成分。方法：采用溶剂萃取法和抗癫痫活性实验，确定何种溶剂提取物抗癫痫活性比较强，并对活性较强提取物的化学成分加以分离，进行结构鉴定。结果：抗惊厥活性物质分别存在于乙醇、乙醚、丙酮和水层提取物中，其中丙酮提取物可使其抗惊厥的潜伏期由对照组的（8．6±1．9）min延长至（21．4±6．7）min；对丙酮提取物进行进一步研究，证明抗惊厥活性的有效成分为伞形花内酯，其作用可使抗惊厥的潜伏期由对照组的（8．6±1．9）min延长至（18．1±4．3）min。结论：初步实验证明瑞香狼毒具有抗惊厥作用，伞形花内酯是有效成分之一。     

瑞香狼毒丙酮提取物抗惊厥作用研究

目的　研究瑞香狼毒丙酮提取物 (AESC)抗惊厥作用。方法　采用五种动物惊厥模型 ,测定AESC时效关系 ,抗惊厥效应 ,并分析量效关系。结果　AESC能提高电刺激大鼠皮层惊厥阈值 ,384mg/kg灌胃和 174mg/kg腹腔注射 0 5～ 1h起效 ,2～ 3h达高峰 ,作用持续 7～ 10d ;而丙戊酸镁 15 0mg/kg腹腔注射作用虽强 ,但其维持时间仅 8h。AESC对小鼠听源性惊厥实验 (AS)、最大电休克惊厥实验 (MES)、戊四唑惊厥实验 (MET)均具有剂量依赖性对抗作用 ,其抗AS、MES、MET的ED50 分别为 10 3 0 5、12 3 83和 132 0 1mg/kg。AESC亦能拮抗大鼠海人藻酸惊厥 ,明显减少湿狗样颤抖 (WDS) (P <0 0 5 ) ,有效延长惊厥潜伏期 (P <0 0 5 )。结论　AESC对多种动物惊厥模型有效 ,是一种作用持续时间长 ,抗痫谱广的抗癫痫物质 ,其作用性质与丙戊酸镁相似。     

瑞香狼毒提取物对肝癌原位移植瘤小鼠的生命延长作用

目的观察瑞香狼毒提取物对肝癌原位移植瘤小鼠的生命延长作用。方法从山西省吕梁山区采集瑞香狼毒,采用水提醇沉的方法制备药物;建立小鼠肝癌原位移植瘤动物模型,采用灌胃给药方法,观察瑞香狠毒提取物对荷瘤动物的生命延长作用。结果瑞香狼毒提取物高、中、低剂量组小鼠平均生存时间分别为(14.7±1.9)d、(13.0±3.4)d和(16.2±3.4)d,模型对照组小鼠平均生存时间为(12.9±2.0)d,阳性对照组小鼠平均生存时间为(12.7±3.4)d,与模型对照组比较,瑞香狼毒低剂量组生命延长率为25.15%,与模型对照组比较差异有统计学意义(P<0.05)。结论瑞香狼毒提取物在适当剂量下能延长肝癌H22荷瘤小鼠的生存时间,对实验性小鼠肝癌可以起到显著的抑制作用。     

狼毒的有效成分及其药理活性研究进展

狼毒是毒属植物瑞香科瑞香狼毒 (Stellera chamaejasmeL.)或大戟科狼毒大戟 (Euphorbia fischeriana Stued.)、月腺大戟 (Euphorbia ebracteolata Hayata.)的根 ,有逐水祛痰、散结杀虫之功效 ,为常用中药。近年的研究发现 ,狼毒提取物对肿瘤细胞有较强的抑制活性 ,此外还有抗菌和抗病毒作用 ,是一个理想的天然药物开发品种。1 　 化学成分研究1 .1　瑞香狼毒　六十年代初 ,我国的研究者从瑞香狼毒的根中分离出一种酸性物质 ,定为狼毒素 (chamaejamine) ,后来确定了其双氢双黄酮的结构。目前瑞香狼毒中已知的成分主要有倍半萜内酯、二萜生…     

从木兰科植物中分得新的三萜类化合物

木兰科植物异味南五味子(Kadsuraheteroclita)或南五味子(Kadsuralongipedunculata Finet Gagn)用有机溶媒(如甲醇、乙醇、丙酮、乙酸乙酯)提取,提取物经硅胶柱层、制备性硅胶柱层、高效液相色谱分离,以展开剂(如乙醚、石油醚、正己烷、乙酸乙酯、苯、甲苯丙酮、甲酸、甲醇、乙醇)展开,即可得到结构为(I)的新的三萜类化合物。     

浅析决明子降血脂的有效成分

目的 简要分析决明子降血脂的有效成分.方法 将决明子研成粗粉,按系统溶剂提取法制取决明子正丁醇提取物.将决明子的正丁醇提取物上AB-8大孔吸附树脂,依次通过水、20%乙醇、80%乙醇洗脱,得到80%乙醇洗脱物.然后将洗脱物分别经过硅胶柱和氯仿-甲醇梯度洗脱,分段收集.然后将分段收集液经过硅胶柱层析(石油醚一丙酮梯度洗脱)、Spehadex LH-20柱层析(甲醇一水梯度洗脱)、C18柱层析(甲醇一水梯度洗脱)得到六种化合物.最后通过运用低密度脂蛋白受体(LDLR)报告基因模型对六种化合物的有效成分进行分析.结果 化合物Ⅱ能明显增强荧光素酶的活性,说明其能明显增强低密度脂蛋白的基因表达,从而有效的降低血脂含量.结论 化合物Ⅱ(橙黄决明素)为决明子降血脂的有效成分.     

瑞香狼毒水提物对有机体的毒性研究

<正> 在中药抗癌筛选中,已发现瑞香狼毒(telleraChamaejasme L.)对移植性实体瘤与白血病有较强的抑制作用,临床多用来治疗晚期癌症,但关于瑞香狼毒对机体毒性的报道较少。本文报告瑞香狼毒水提物对昆明小鼠机体脂质过氧化的作用。     

从华中五味子分得的一个新木脂素

华中五味子(Schisandra sphenanthera)是一种中国的药用植物。它的果实经空气干燥粉碎后依次用石油醚、乙醚、甲醚提取,其乙醚提取物经硅胶(20～30μ)柱(3×60cm)层折,依次用石油醚、石油醚—10％丙酮、石油醚—20％丙酮、石油醚—40％丙酮洗脱,分别得到部分P_1、P_2、P_3、P_4。P_2部分再经硅胶(40μ)柱(1.5×25cm)层析,用逐渐增加乙酸乙酯含量(15～50％)的石油醚洗脱,得出粗品ganschisandrine(1),经正己烷—乙醚重结晶,得到白色片状结晶(1),C_(22)H_(25)O_5mp114～115℃,〔a〕~D_(20)+173.1~o(C.0.26,氯     

北豆根不同组分发挥抗炎作用的安全范围研究

目的研究北豆根水提、醇提组分发挥抗炎作用的治疗指数和安全范围。方法建立琼脂皮下注射致小鼠肉芽肿模型,给不同剂量的北豆根水提、醇提组分连续7天灌胃,观察北豆根不同组分抗炎作用,用Bliss法计算各组分发挥抗炎药效ED50、ED95;依据本实验室前文报道的北豆根不同组分急性毒性研究结果,用Bliss法计算各组分急性毒性的LD50,LD5,求得北豆根不同组分发挥抗炎作用的治疗指数(TI),安全系数(SF)。结果北豆根不同组分对炎症模型有明显的抗炎作用,呈现明显的量效关系,且醇提组分抗炎作用大于水提组分。北豆根水提、醇提组分对肉芽肿模型小鼠的抗炎安全范围TI、SF分别为57.532、17.4702和45.844、9.800。结论北豆根醇提组分对炎症模型的抗炎效果大于水提组分,但水提组分发挥抗炎作用的安全范围大于醇提组分。因此,在临床应用北豆根醇提组分时更应密切注意不良反应的发生并加强用药监测。     

Control of nerve agent-induced seizures is critical for neuroprotection and survival

This study evaluated the potency and rapidity of some anticholinergics (atropine, biperiden, and trihexyphenidyl) and benzodiazepines (diazepam and midazolam) as an anticonvulsant treatment against seizures induced by six nerve agents (tabun, sarin, soman, cyclosarin, VR, and VX) and summarized the relationship between anticonvulsant activity and nerve agent-induced lethality and neuropathology. Guinea pigs, previously implanted with cortical electrodes for EEG recording, were pretreated with pyridostigmine bromide (0.026 mg/kg im) 30 min prior to challenge with 2x LD50 dose (sc) of a given nerve agent; in a separate experiment, animals were challenged with 5x LD50 sc of soman. One minute after agent challenge the animals were treated im with 2 mg/kg atropine SO(4) admixed with 25 mg/kg 2-PAM Cl. Five minutes after the start of EEG seizures, animals were treated im with different doses of anticholinergics or benzodiazepines and observed for seizure termination. The time to seizure onset, the time to seizure termination, and 24-h lethality were recorded. The anticonvulsant ED50 of each drug for termination of seizures induced by each agent was calculated and compared. Brain tissue from animals that survived 24 h was examined for pathology. All drugs were capable of terminating seizure activity, with midazolam and trihexyphenidyl being significantly more potent than the other drugs, and midazolam being more rapid in controlling seizure than atropine, trihexyphenidyl, or diazepam against each agent. Seizures induced by sarin or VX required lower doses of all the test anticonvulsants. The dose of a given drug that was an effective anticonvulsant against a 2x LD50 challenge of soman was equally effective against seizures induced by a 5x LD50 challenge. All nerve agents were capable of producing neuropathology. Seizure control was strongly associated with protection against acute lethality and brain pathology.     

Organophosphorus nerve agents-induced seizures and efficacy of atropine sulfate as anticonvulsant treatment.

The ability of five organophosphorus nerve agents (tabun, sarin, soman, GF, and VX) to produce brain seizures and the effectiveness of atropine as an anticonvulsant treatment against these nerve agents were studied in two different animal models--the rat and guinea pig. All animals were implanted with cortical electrodes for EEG recordings. Five minutes after the start of nerve agent-induced EEG seizures, animals were treated intramuscularly (IM) with different doses of atropine sulfate and observed for seizure termination. The anticonvulsant ED50 of atropine sulfate for termination of seizures induced by each nerve agent was calculated and compared. In the rat model, selected oximes were administered either before, concurrent with, or following challenge with a 1.6 x LD50 dose of a given nerve agent to maximize seizure development with certain agent/oxime combinations. The choice and the timing of oxime administration significantly effected the incidence of seizure development by different nerve agents. When oxime administration did not effect seizure development (tabun, soman) the anticonvulsant ED50 for atropine sulfate was the same, regardless of the nerve agent used to elicit the seizure. When oxime administration reduced the incidence of seizure occurrence (sarin, GF, VX), the anticonvulsant ED50 dose of atropine sulfate for a nerve agent was lower. In the guinea pig model, animals were pretreated with pyridostigmine prior to challenge with 2 x LD50 of a given agent, and treated 1 min later with atropine sulfate (2 mg/kg) and 2-PAM (25 mg/kg). Under these conditions, the incidence, latency of seizure development, and anticonvulsant ED50s of atropine for soman-, tabun-, and GF-elicited seizures were virtually identical. With sarin, although the latency of seizure development was the same as with soman, tabun, and GF, seizures occurred with a lower incidence, and the anticonvulsant ED50 of atropine was lower. With VX, the latency of seizure development was notably longer, while the incidence of seizure development and anticonvulsant ED50 of atropine were significantly lower than with soman, tabun, or GF. In both models, a lower incidence of seizure development predicted a lower anticonvulsant dose of atropine. In the rat, the incidence of seizure development and the anticonvulsant effectiveness of atropine was highly dependent on the oxime used. In the guinea pig, higher doses of atropine sulfate were required to control soman-, tabun-, or GF-induced seizures, perhaps reflecting the lower cholinesterase reactivating ability of 2-PAM against these agents.     

Screening of the anticonvulsant activity of some plants from Fabaceae family in experimental seizure models in mice

BACKGROUND AND PURPOSE OF THE STUDY: Fabaceae is the third largest family of flowering plants. Lack of essential oils in the plants of this family can be an advantage in search for safe and effective medicines. In this study the anticonvulsant effect of the leaves of Albizzia julibrissin, Acacia juliflora, Acacia nubica and aerial parts of Astragalus obtusifolius was evaluated in pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure tests. METHODS: The hydroalcoholic extracts of the plants were obtained by percolation. Different doses of the extracts were injected to the mice intraperitoneally (i.p.) and occurrence of clonic seizures induced by PTZ (60 mg/kg, i.p.) or tonic seizures induced by MES (50 mA, 50Hz, 1sec) were monitored up to 30 min after administration. Acute toxicity of the extracts was also assessed. The safe and effective extract was then fractionated by dichloromethane and anticonvulsant activity of the fractions was determined. Finally, the constituents of the extract and the fractions were screened by thin layer chromatography. RESULTS: Among the extracts, only A. obtusifolius extract showed low toxicity and protective effect against clonic seizures with ED50 value of 3.97 g/kg. Fractionation of the extract led to increase in anticonvulsant activity and ED50 value of 2.86 g/kg was obtained for the aqueous fraction. Phytochemical screening revealed the presence of alkaloids, flavonoids, anthrones and saponins in the aqueous fraction. MAJOR CONCLUSION: The presence of anticonvulsant compounds in A. obtusifolius suggests further activity-guided fractionation and analytical studies to find out the potential of this plant as a source of anticonvulsant agent.     

New anticonvulsants derived from 4-allyl-2-methoxyphenol (Eugenol): comparison with common antiepileptics in mice

The anticonvulsant activity (ED50) of three synthetic eugenol derivatives - phenyleugenol (PE), benzyleugenol (BE), phenylethyleugenol (PEE) - was compared to that of common antiepileptics - diphenyl-hydantoin (DPH), phenobarbital (PB), diazepam (DZ) - and the naturally occurring methyleugenol (ME) in the maximal electroshock seizure (MES) test and the subcutaneous pentylenetetrazol-induced minimal seizure (s.c. PTZ) test. Neurotoxicity (ND50) and lethality (LD50) were determined in order to evaluate the protective index (PI = ND50/ED50) and the therapeutic index (TI = LD50/ED50). BE, PE and PEE are shown to be effective anticonvulsants by the MES test in mice with PIs equal to or higher than that of PB and DZ. Furthermore, BE and PEE were significantly more potent in rats than in mice. Experiments on ;the duration of protection revealed an immediate onset, a steady decline within the following 4 h and reappearance of activity 6-8 h after injection of PE, BE, and PEE but not ME. In the s.c. PTZ test in mice, the eugenol derivatives were active in increasing the latency to the first minimal seizure but less active in its prevention. As to the TIs, PEE showed a smaller margin of safety by the two tests than BE and PE. The latter compounds have high LD50s and consequently high TIs.     

吴茱萸不同组分镇痛作用及安全范围研究

目的研究吴茱萸不同组分发挥镇痛作用的治疗指数和安全范围。方法采用经典的急性毒性试验方法,进行吴茱萸不同组分的急性致死量试验;采用经典的小鼠热板法,进行吴茱萸不同组分的镇痛药效实验。采用Bliss法,计算各组分的急性毒性试验的LD50和LD5以及发挥镇痛药效的ED50和ED95,求得不同组分发挥镇痛作用的治疗指数(TI),安全系数(SF)。结果吴茱萸挥发油LD50值为2.6995mL.kg-.1d-1,LD5值为1.9853m.lkg-.1d-1;ED50值为0.4625mL.kg-.1d-1,ED95值为0.9996 mL.kg-.1d-1;计算得TI为5.837,SF为1.986。吴茱萸水提组分无法作出LD50,MTD试验结果按含生药量计算为80.0 g.kg-.1d-1;ED50值为1.3515 g.kg-1.d-1,ED95值为4.3435 g.kg-1.d-1。结论吴茱萸水提组分和挥发油组分均有一定的镇痛作用,并呈现一定的量效关系,且吴茱萸水提组分发挥镇痛作用的安全范围大于挥发油组分。     

香加皮不同组分发挥镇痛作用的安全范围研究

目的研究香加皮不同组分发挥镇痛作用的安全范围。方法用热板法观察香加皮不同组分镇痛作用,依据本实验室前文报道的香加皮不同组分急性毒性研究结果,用Bliss法分别计算各组分发挥镇痛药效的ED50、ED95、和急性毒性的LD50,LD5,求得香加皮不同组分发挥镇痛作用的治疗指数(TI),安全系数(SF),以此评价其发挥镇痛作用的安全范围。结果香加皮不同组分均有明显的镇痛作用,呈现明显的量效关系,不同组分发挥镇痛作用的安全范围有所不同,香加皮水提提组分ED50=1.5698 g.kg-1.d-1,TI=59.611,SF=17.4702,其ED95和LD5分别相当于药典规定的人日用量的48.0和839.0倍。香加皮醇提组分ED50=1.3687 g.kg-1.d-1,TI=44.853,SF=14.2405,其ED95和LD5分别相当于药典规定的人日用量的35.7和509.0倍。结论香加皮水提组分发挥镇痛作用的安全范围大于醇提组分,在应用香加皮醇提组分时更应密切注意不良反应的发生并加强用药监测。     

Etifoxine: evaluation of its anticonvulsant profile in mice in comparison with sodium valproate, phenytoin and clobazam

The anticonvulsant potential of 6-chloro-2-(ethylamino)-4-methyl-4-phenyl-4H-3,1-benzoxazine (etifoxine), a non-benzodiazepine tranquilizer, was evaluated in mice in comparison to valproate, phenytoin and clobazam. Maximal seizures were induced by electroshock (MES) and the chemical convulsants pentetrazol (PTZ), picrotoxin (PTX), bicuculline (BIC), isoniazid (INH), nicotine (NIC) and strychnine (STR). Tonic extensor convulsions were prevented by etifoxine in the following rank order of potency (ED50 values with seizure tests): 39.5 (PTX), 101 (PTZ), 101 (MES), 154 (INH), 181 (NIC), 397 (BIC), and greater than 800 mg/kg p.o. (STR). Clonic seizures were induced by threshold doses of PTZ, PTX and pilocarpine (PIL) and antagonized by etifoxine at ED50 values of 181 (PIL), 221 (PTZ), and greater than 800 mg/kg p.o. (PTX). Hence, etifoxine blocked both tonic and clonic seizures but was more potent against the tonic component. The anticonvulsant profile of etifoxine appeared similar to that of valproate. However, in terms of potency, protective indices (ED50 rotarod/ED50 seizure test) and therapeutic indices (LD50/ED50 seizure test) etifoxine was on an average 3.7, 12 and 14 times superior to valproate, respectively. It is concluded that etifoxine has a marked anticonvulsive potential and may be beneficially used in epileptic disorders, especially of the grand mal type.     

Preclinical evaluation of CHF3381 as a novel antiepileptic agent

CHF3381 [n-(2-indanyl)-glycinamide hydrochloride] has been selected on the basis of a screening program as the compound displaying the highest anticonvulsant activity in the maximal electroshock seizure (MES) test and the best therapeutic index with reference to the rotarod test in mice and rats. In this study, the antiepileptic activity and the behavioural toxicity of CHF3381 were characterised in multiple model systems. CHF3381 effectively prevented MES-induced convulsions when administered i.p. (ED50, 24 mg/kg and 7.5 mg/kg) or p.o. (ED50, 21 mg/kg and 21 mg/kg) in both mice and rats, respectively. The time course of oral anti-MES activity in the rat was related to the brain concentration profile of unchanged CHF3381. Interestingly, the brain drug levels were about 4-5 times higher than in plasma. CHF3381 was very effective in mice against picrotoxin-, and i.c.v. N-methyl-D-aspartate (NMDA)-induced hind limb tonic extension (ED50 Approximately/=10 mg/kg), but was a weaker antagonist of 4-amynopyridine- and bicuculline-induced tonic seizures (ED50 approximately/=100 mg/kg), and ineffective against pentylentetrazole- and picrotoxin-induced clonic seizures. CHF3381 antagonised the behavioural effects and lethality of i.p. administered NMDA (ED50 = 57 mg/kg p.o.), indicating that the compound may act as a functional NMDA antagonist. In keeping with this idea, CHF3381 weakly displaced [(3)H]-TCP from binding to NMDA receptor channels (Ki, 8.8 microM). In the rat amygdala kindling model, CHF3381 was more efficient against kindling development than against kindled seizures (minimally active dose = 80 vs. 120 mg/kg i.p). Furthermore, it significantly increased the seizure threshold in kindled rats at relatively low doses (40 mg/kg i.p.). In contrast with MK-801-induced hyperactivity, CHF3381 moderately reduced the spontaneous locomotor activity in mice at anticonvulsant doses. Toxic effects on motor performance (rotarod test) were found at high doses only (TD50 approximately/= 300 mg/kg p.o., congruent with 100 mg/kg i.p. in both mice and rats). Furthermore, CHF3381 did not impair passive avoidance and Morris water maze responding in the therapeutic range of doses. Finally, the development of tolerance after repeated doses was negligible. These data indicate that CHF3381 exerts anticonvulsant and antiepileptogenic effects in various seizure models and possesses good therapeutic window, with scarce propensity to cause neurological side-effects.     

Pharmacological properties of the antiinflammatory agent 10-methylamine-11-H-indeno-[1,2-b]quinolin-11-one (MB432)

10-Methylamine-11-H-indeno [1,2-b] quinolin-11-one (MB432) was found to be a prostaglandin synthetase inhibitor, to display antiinflammatory activity in carrageenin edema and cotton pellet granuloma tests in rats, and to exert analgesic action in paw pressure test in rats and in the writhing test in mice. The therapeutic index (LD50/ED50) for antiinflammatory and analgesic effect of MB432 is higher than that of indomethacin (IND) and phenylbutazone (PHB). The acute toxicity of MB432 is low but the drug showed high ulcerogenic activity. The ratio of medium ulcerogenic to median antiinflammatory and analgesic doses of MB432 is comparable to that of PHB but higher than for IND.