Fetal toxicity of Solanum lycocarpum (Solanaceae) in rats

Lobeira (Solanum lycocarpum) is a Brazilian plant used as a hypoglycemic agent. In this study, the toxic effects of lobeira were evaluated during the fetogenesis period. Twenty pregnant Wistar rats were randomly allocated into two groups: control and treated, which received, via oral gavage, 0.5 ml of distilled water or 100 mg of the lobeira powder/kg of body weight, respectively, during days 17-20 of pregnancy. Maternal toxicity was evaluated by body weight, food intake, piloerection, locomotor activity, diarrhoea and vaginal bleeding. Euthanasia was done on 21st day, when ovaries, fetuses and their respective placentas were removed. Resorptions, live and dead fetuses were recorded. External malformations and fetal body, brain, liver, lung and kidneys were also weighed. No clinical signs of maternal toxicity were observed. The placenta weights of the treated rats were lower than those of the control (P<0.01). Lungs (P<0.01) and kidneys (P<0.02) of the fetuses treated with lobeira were also significantly reduced, suggesting a fetotoxic effect of this plant.     

补肾活血颗粒急性毒性实验研究

目的:研究补肾活血颗粒对昆明种(KM)小鼠及SD大鼠的急性毒性,为临床安全用药提供依据。方法:将40只健康KM小鼠及40只健康SD大鼠分别随机分为给药组和对照组,每组20只,给药组一天内以最大给药浓度、动物可承受的最大给药体积给于补肾活血颗粒药液2次,对照组给予等量蒸馏水,观察14 d,最后一天处死所有受试动物,记录脏器指数,计算最大给药量(MLD)及耐受倍数,主要脏器进行石蜡包埋、切片,观察病变情况。结果:给药组的雌性KM小鼠体重增长与对照组比较,有非常显著性差异(P<0.01),给药组的雄性SD大鼠体重增长与对照组比较,有显著性差异(P<0.05);各组脏器指数均无显著性差异(P>0.05)。解剖观察,受试动物各组织脏器无肉眼可见病变。大鼠、小鼠的最大耐受倍数分别为200倍和1000倍。与对照组相比,给药组的组织病理学观察并无明显差别。结论:补肾活血颗粒可延缓雌性KM小鼠的体重增长,并且也可对雄性SD大鼠体重增长产生影响,但对各脏器均无毒性损伤,安全无毒。     

壮药土甘草水提物及醇提物毒理学研究

目的 观察土甘草水提物和醇提物对小鼠灌胃给药的急性毒性.方法 以土甘草水提物1.57 g/ml,醇提物2.40 g/ml,最大剂量40 ml/kg分别对小鼠灌胃给药,观察其急性毒性.结果 给药后,小鼠均蜷卧少动,24 h后此症状消失.观察7 d,小鼠的行为、进食、皮毛、眼和粘膜、呼吸、四肢活动和体重均无异常,未出现其它毒性反应.土甘草水提物对小鼠灌胃给药的最大耐受量为62.8 g生药/kg;醇提物对小鼠灌胃给药的最大耐受量为96.0 g生药/kg.结论 土甘草水提物对小鼠灌胃给药的最大耐受量为62.8 g生药/kg;醇提物对小鼠灌胃给药的最大耐受量为96.0 g生药/kg.未出现其它毒性反应.     

Chronic toxicity study of Portulaca grandiflora Hook

We investigated the toxic effects of Portulaca grandiflora aqueous extract given to male and female Wistar rats for 6 months. The rats were divided into five groups of each sex that were control groups, three experimental groups and recovery groups. The control groups received 5 ml of distilled water/kg per day. The experimental groups were orally given the water extract of Portulaca grandiflora at doses of 10, 100 and 1000 mg/kg per day. The recovery groups received 1000 mg/kg per day for 6 months and were continued husbandry without giving the extract for further 14 days. Changes in the body weights, actual and relative organ weights were not significantly demonstrated in all groups throughout the study. No significant alteration in hematological, biochemical and histopathological parameters was observed in all female groups given the extract. It was found that any significant changes in hematological and biochemical parameters in the male rats at the doses of 100 and 1000 mg/kg per day were not dose-related. In addition, no histopathological lesions were observed in the male animals. Our results suggested that the water extract of Portulaca grandiflora at the doses given in the study did not induce any detrimental effects in the rats.     

Antioxidant activity of Nelumbo nucifera (sacred lotus) seeds

Antioxidant activity of hydro alcoholic extract of Nelumbo nucifera seeds (HANN) was studied using in vitro and in vivo models. Total phenolic content in HANN was found to be 7.61 +/- 0.04% (w/w). Characteristic HPTLC fingerprints of HANN were also made using different solvent systems. The HANN exhibited strong free radical scavenging activity as evidenced by the low IC(50) values in both DPPH (1,1-diphenyl-2-picryl hydrazyl) (6.12 +/- 0.41 microg/ml) and nitric oxide (84.86 +/- 3.56 microg/ml) methods. The values were found to be less than those of rutin, the standard used. Acute toxicity of HANN was evaluated in Swiss Albino mice, no signs of toxicity were observed up to the oral dose of 1,000 mg/kg body weight. Administration of HANN to Wistar rats at 100 and 200 mg/kg body weight for 4 days prior to carbon tetrachloride (CCl(4)) treatment caused a significant dose dependent increase (p < 0.05 to p < 0.001) in the level of superoxide dismutase (SOD) and catalase and a significant decrease (p < 0.05 to p < 0.001) in the level of thiobarbituric acid reactive substances (TBARS), when compared to CCl(4) treated control in both liver and kidney. These changes observed at 100 mg/kg body weight treatment were comparable to those observed for standard Vitamin E at 50 mg/kg treatment. Nelumbo nucifera seeds contain alkaloids, saponins, phenolics and carbohydrates. The results support significant antioxidant nature of HANN.     

藏药藏降脂胶囊毒理学研究

目的:观察藏降脂胶囊的毒理作用。方法:急性毒性实验:以一日最大耐受量测定小鼠灌胃藏降脂胶囊的急性毒性反应;长期毒性实验:以1g/kg·d、2.1g/(kg·d)和4.2g/(kg·d)(相当于临床拟用药量的25、50、100倍)各剂量组,连续灌胃90天,对照组给等量的蒸馏水。观察实验期间大鼠行为、外观、进食量、饮水量、体质量,测定给药45天、90天及停药15天大鼠血象指标和血液生化指标、主要脏器系数、解剖学、病理组织形态学。结果:其1日最大耐受量为17.25g/kg(相当于临床拟用药量的441倍)。各剂量组连续给药90d,大鼠生长发育良好,无死亡,实验动物外观、行为活动、体重增长、主要脏器系数、血液生化、血象等指标及对主要脏器病理组织学检查与空白对照组比较均无显著性差异。结论:藏降脂胶囊通过小鼠急性毒性实验和大鼠长期毒性实验未发现明显毒性反应,临床剂量是安全的。     

Antiulcer action of the hydroalcoholic extract and fractions of Davilla rugosa Poiret in the rat

Davilla rugosa Poiret ("Cipó- Caboclo") is commonly used in Brazilian folk medicine. The hydroalcoholic extract of the stems (HE) was fractionated with chloroform (CF), chloroform/ethyl acetate (CAF), ethyl acetate (AF), ethyl acetate/ethanol (AEF), ethanol (EF), and ethanol/water (EWF). The hydroalcoholic extract (HE) and fractions of the stems of D. rugosa Poiret were investigated for possible anti gastric ulcer properties. These extracts were shown to protect rats from developing gastric ulcers induced by two acute models: HCl/ethanol (400 mg/kg i.p.) and immersion-restraint stress (15 and 30 mg/kg of the HE and 15 mg/kg either of the ethanol or the ethanol/water fractions, p.o.). The daily oral dose of 800 mg/kg of HE for 30 consecutive days was tested for possible toxic effects. There were no modifications in body weight, water or food intake or in the external aspect of kidneys, spleen, lungs and liver. The only difference observed was a decrease of liver weight. These results suggest that the D. rugosa Poiret HE has an antiulcer activity in rats and the active components are in the two more polar fractions.     

Studies on the toxicity of Punica granatum L. (Punicaceae) whole fruit extracts

Current investigation focuses on the toxicity evaluation of whole fruit hydroalcoholic extract of Punica granatum L. (Punicaceae), used in Cuban traditional medicine a.o. for the treatment of respiratory diseases. Previous findings on the anti-influenza activity of Punica granatum extracts has given support to the ethnopharmacological application. In our study, in chick embryo model, it was found that doses of the extract of less than 0.1 mg per embryo are not toxic. The LD50 of the extract, determined in OF-1 mice of both sexes after intraperitoneal administration, was 731 mg/kg. Confidence limits were 565-945 mg/kg. At the doses of 0.4 and 1.2 mg/kg of extract, the repeated intranasal administration to Wistar rats produced no toxic effects in terms of food intake, weight gain, behavioural or biochemical parameters, or results of histopathological studies. We conclude that toxic effects of Punica granatum fruit extract occurred at higher doses than those effective in the models where the anti-viral activity has been studied or than those doses used in Cuban folk medicine.     

藏药仁青常觉的毒理学实验研究

目的:观察藏药仁青常觉的毒理作用。方法:急性毒性实验:以一日最大耐受量测定小鼠灌胃仁青常觉的急性毒性实验。长期毒性试验:给大鼠灌胃给药3个不同剂量的仁青常觉,低剂量组(0.350g/kg)、中剂量组(0.700g/kg)和高剂量组(1.400g/kg),连续90天,空白对照组ig蒸馏水,观察大鼠一般状况、体重、摄食量,测定给药90天及停药15天血液生化指标、脏器系数、解剖学及病理组织。结果:测得小鼠最大耐受量大于30g/kg(此剂量相当于临床成人拟日服剂量的2142倍),未发现任何不良反应及死亡现象;各剂量组连续给药90天,未发现死亡,动物生长发育良好,外观正常,行为活动无异常,主要脏器系数、血液生化、血象等指标与空白对照组比较均无显著性差异。结论:通过实验,未发现明显毒性反应,证明临床剂量是安全的。     

加味小陷胸汤基于核因子-κB信号通路对非小细胞肺癌荷瘤小鼠的影响实验研究

目的:探讨加味小陷胸汤基于核因子κB(NF-κB)信号通路对非小细胞肺癌荷瘤小鼠的影响。方法:选取SPF级健康雄性C57BL/6小鼠75只,分为对照组15只和造模组60只。造模组采用人非小细胞肺癌A549细胞株右腋下接种建立非小细胞肺癌荷瘤模型,对照组给予等量生理盐水右腋下皮下注射。造模成功后,将造模组小鼠随机分为模型组、加味小陷胸汤低、高浓度组及顺铂组,各15只。模型组和对照组分别予以无菌生理盐水5 ml/kg,腹腔注射,1次/d +蒸馏水5 ml/kg,灌胃,1次/d; 加味小陷胸汤低、高浓度组分别予以无菌生理盐水5 ml/kg,腹腔注射,1次/d +8 mg/ml、16 mg/ml加味小陷胸汤药液5 ml/kg,灌胃,1次/d; 顺铂组予以0.4 mg/ml顺铂溶液5 ml/kg,腹腔注射,1次/d +蒸馏水5 ml/kg,灌胃,1次/d。所有小鼠均连续给药14 d。对小鼠肿瘤体积、瘤重和生长抑制率、肿瘤组织细胞凋亡率、肿瘤组织含半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)、NF-κB、B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达水平进行检测。结果:治疗后,与模型组比较,各组小鼠肿瘤体积、瘤重较低,肿瘤组织NF-κB、Bcl-2表达水平较低,且加味小陷胸汤低浓度组>加味小陷胸汤高浓度组和顺铂组,差异有统计学意义(P<0.05)。与模型组比较,各组小鼠肿瘤生长抑制率较高,肿瘤组织细胞凋亡率较高,肿瘤组织Bax、Caspase-3表达水平较高,且加味小陷胸汤低浓度组<加味小陷胸汤高浓度组和顺铂组,差异有统计学意义(P<0.05)。结论:加味小陷胸汤能剂量依赖性抑制非小细胞肺癌荷瘤小鼠肿瘤生长,促进肿瘤细胞凋亡,其作用可能与抑制NF-κB信号通路,调节凋亡相关蛋白Bcl-2、Bax、Caspase-3表达有关。     

四妙勇安汤活性部位灌胃给药的急性毒性实验研究

目的观察四妙勇安汤活性部位(SMAF)灌胃给药的急性毒性。方法通过预实验,未获得动物的半数致死量,进行最大耐受量试验。选取昆明小鼠及Wistar大鼠各40只,雌雄各半,均分为给药组(20只)及对照组(20只),雌雄各半,给药组采用一次最大浓度和最大容积灌胃给药,小鼠灌胃剂量为6.0 g/kg,大鼠灌胃剂量为3.0 g/kg,对照组灌胃等容积0.5%羧甲基纤维素。观察给药14 d内,大、小鼠的行为、体质量、进食量、死亡率及毒性反应,计算药物的最大耐受量。结果给药后14 d内,与对照组相比,给药组雌雄小鼠、大鼠活动、行为、眼睑、分泌物、呼吸、腹形、排便等均无异常,未见因药物引起的死亡。给药组雌雄小鼠、大鼠给药后7、14 d体质量与对照组同期比较差异无统计学意义(P0.05)。给药组雌雄小鼠、大鼠药后7、14 d进食量与对照组同期比较差异无统计学意义(P0.05)。给药14 d后,处死各组小、大鼠,与对照组比较,给药组均未见脏器明显的肿大、萎缩、坏死、充血、出血、水肿等异常现象。四妙勇安汤活性部位一次性灌胃给药对小鼠最大耐受量6.0 g/kg(相当于人日推荐量的360倍);对大鼠最大耐受量3.0 g/kg(相当于人日推荐量的180倍)。结论 SMAF灌胃给药没有明显毒性。     

不同比例海藻与甘草配伍对大鼠的毒性研究

目的：研究不同比例海藻与甘草配伍对大鼠的毒性作用。方法：32只Wistar大鼠,体重(123±15.3) g,随机分为4组,每组各8只,分别为 正常组(A)和配伍用药组(B,C,D)。正常组用蒸馏水灌胃,B,C,D组用海藻-甘草(1∶1)、海藻-甘草(2∶1)、甘草-海藻(3∶1)灌胃,给药剂量为生 药20 mg·g^-1体重,共35 d,期间观察大鼠的毛色、进食、活动等情况。第36天处死大鼠,对大鼠体重,脏器系数,血常规,血液生化指 标及肝药酶进行检测。结果：海藻与甘草配伍对大鼠毛色、进食、活动、体重、脏器系数无影响,对血液系统、肝功能、心肌酶、肾功能、肝药 酶会产生一定的影响,且与配伍比例有关。结论：海藻甘草不同比例配伍后,对大鼠脏器具有选择毒性作用,并与配伍比例有关。     

瑶药葫芦钻提取物抗肿瘤作用的实验研究

目的研究葫芦钻提取物的抗肿瘤作用。方法体外抗肿瘤活性研究采用MTT比色法,靶细胞采用人肝癌细胞BLE-7404;通过复制小鼠S180,H22腹水瘤和肉瘤动物模型,观察葫芦钻提取物对小鼠平均生命延长率和肿瘤抑制率的影响来评价体内抗肿瘤作用。结果葫芦钻水、醇提取物浓度为20 mg/ml时,对体外培养的肿瘤细胞的抑制率均>50%;葫芦钻水、醇提取物的最大耐受剂量均是150 g/kg;经3次实验,葫芦钻水、醇提取物高、低剂量组对S180腹水瘤小鼠平均生命延长率均>50%,葫芦钻醇提物高剂量组对H22腹水瘤小鼠平均生命延长率>50%。葫芦钻水、醇提取物高、低剂量组对S180肉瘤小鼠平均瘤重抑制率均>30%,对H22肉瘤小鼠平均瘤重抑制率均>50%。结论葫芦钻水、醇提取物具有一定的抗肿瘤作用。     

Teratogenic effects, acute and sub chronic toxicity of the leaf aqueous extract of Ocimum suave Wild (Lamiaceae) in rats

The aqueous extract from the leaves of Ocimum suave was evaluated for acute and sub chronic toxicity and teratogenic effects. Swiss mice were administered single oral doses of 2000, 4000, 6000 and 8000 mg/kg and monitored for death and body weight gained for 7 days (acute toxicity). In sub-acute toxicity, experimental rats, received daily doses of 250, 500 and 1000 mg/kg for 42 consecutive days and the toxic effects were assessed using biochemical and haematological data and histology of vital organs. In a teratogenic study, 1-day pregnant rats were administered orally 500 and 1000 mg/kg of extract daily for 21 consecutive days and 14th day corpora lutea and foetal implants and litter size at birth were noted. Reproductive performance of F(1) generation rats was studied by crossing them at maturity and recording the number, birth weight and physical presentation of the young offspring. Acute intake of extract up to 8000 mg/kg did not produce mortality or significant changes in general behaviour. Sub chronic treatment did not show any change in body and organ weights, feeding habits or behaviour between the control and the treated groups of both sexes. Haematological analysis and blood biochemistry revealed no toxicity effects of the extract. No gross abnormalities or histological changes were observed. Teratogenic and fertility studies did not reveal any toxic manifestations or foetal abnormalities. The leaf aqueous extract of Ocimum suave is non toxic in acute and sub chronic intake.     

灯盏花素对正常和眼底病变模型大鼠影响的比较研究

目的：通过比较灯盏花素对正常和眼底病变大鼠的影响，探索以模型动物评价中药安全性的可行性及注意事项。方法：将160只SD大鼠随机分为空白对照组、模型组、灯盏花素(正常动物)2.0 g/kg组(简称正常-高组)、灯盏花素(模型动物)0.8 g/kg(简称模型-低组)、灯盏花素(模型动物)2.0 g/kg组(简称模型-高组)，每组32只，雌雄各半。各组的给药容积均为15 mL/kg,1次/d，连续给予灭菌动物饮用水和浓度为0.05、0.13 g/mL的灯盏花素混悬液9 d后，模型组和模型-低、高组以0.06 g/kg剂量腹腔注射碘酸钠(NaIO3)溶液1次造模，空白对照组、正常-高组同法注射氯化钠注射液。造模次日各组继续给药，实际给药天数分别为11、15、29、36 d，停药后继续观察至造模后第41、62天。试验期间每天观察动物一般体征、每周称量体质量，于造模后第3、7、21、28、41、62天随机抽取大鼠腹主动脉采血进行血清生化学指标检测，主要脏器称重和组织病理学检查。结果：灯盏花素对大鼠体质量和正常大鼠一般体征均没有影响，但可减少因注射NaIO3引起稀便的大鼠数量；正常-高组大鼠血清生化学指标无毒理学意义的轻微波动，但模型-低组和模型-高组大鼠造模初期血清化学指标升高。连续给药11 d可使模型-高组雌鼠肾上腺重量和正常-高组雄鼠胸腺重量增大，给药15 d可使正常雌鼠肾上腺重量减轻，上述指标组间比较均具有显著性差异(P<0.05)。灯盏花素两个剂量对正常大鼠脏器组织形态均没有影响，但可明显减轻模型大鼠的视网膜病变。结论：灯盏花素模型大鼠重复给药的无毒性反应剂量(NOAEL)低于正常动物，以模型动物开展临床前安全性评价存在降低受试物安全剂量范围的可能性，在模型动物的选择方面应排除造模药物的影响，包括考虑造模药物和评价药物之间的相互作用和模型背景数据的建立等。     

纳豆冻干粉对小鼠免疫功能的影响

目的 观察纳豆冻干粉对小鼠免疫功能的影响。方法分别以80mg／kg、160mg／kg、320mg／kg三个剂量纳豆冻干粉灌胃喂养小鼠,并设蒸馏水对照组;30d后,检测小鼠体质量、胸腺和脾脏指数、NK细胞活性、单核-巨噬细胞吞噬能力等。结果纳豆冻干粉对小鼠体质量无明显影响;中、高剂量组小鼠NK细胞活性、巨噬细胞吞噬率、吞噬指数均较对照组显著提高（P〈0．05）。结论纳豆冻干粉具有增强小鼠免疫功能的作用。     

Phytochemical study of Solanum lycocarpum (St. Hil) unripe fruit and its effects on rat gestation

Solanum lycocarpum, St. Hil (Solanaceae) is a common native shrub in the Brazilian cerrado. The fruits are used in folk medicine as a hypoglycaemic agent in the management of diabetes, obesity and to decrease cholesterol levels. In this study the glycoalkaloids, solamargine and solasonine, were isolated from unripe fruits of S. lycocarpum. To evaluate the effects of the fruits on gestation, pregnant rats (n=25) were fed from day 6 to 22 with chow containing 10% of dried and ground unripe fruits. The control group (n=21) received regular chow. During and after the treatment period the dams showed reduced body weight and slower body weight gain, even with no change in food and water intake, evidencing mild maternal toxicity. Gestation was not significantly impaired, although experimental fetuses presented reduced body length at birth. Also, 20% of the treated dams showed one or two dead pups at birth. On day 22 of gestation and on post-natal day 1, the levels of metabolites of the sex hormones oestradiol, progesterone and testosterone were measured in faeces by radioimmunoassay. On post-natal day 1, tissue portions from the dams were collected for histopathological evaluation. No alterations were detected in either study. The results suggest that S. lycocarpum fruit did not impair gestation, however, it did promote mild maternal toxicity and mild fetotoxic effects if ingested as a food source during the gestation period. This study has implications for pregnant women, who employ phytotherapeutic formulations under the impression that they are harmless.     

Anti-spermatogenic activity of ethanol extract of Dalbergia sissoo Roxb. stem bark

The study was undertaken to evaluate the anti-spermatogenic efficacy of ethanol extract of stem bark of Dalbergia sissoo Roxb. For the in vitro study, semen samples were obtained from 15 healthy fertile men aged 25-35 years. Sperm motility was examined by the Sander-Cramer method. A dose-dependent and time-dependent effect of ethanol extract on sperm motility and sperm viability were observed. Various concentrations affected the motility of sperm. Ethanol extract at a concentration of 20 mg/mL caused complete immobilization within 3 minutes. Sperm viability and hypo-osmotic swelling was significantly reduced at this concentration. The in vivo studies were carried out on Swiss male albino mice. Ethanol extract at a dose of 200 mg/kg body weight resulted in a significant decrease (p<0.001) in weight of the testis and epididymis. A significant decrease (p<0.01) in sperm motility and sperm count in the epididymis were observed. Histological changes in the epididymis and testis were also investigated.     

粉防己碱与可乐定对小鼠和大鼠吗啡躯体依赖的影响

目的:观察粉防己碱(Tet)与可乐定对吗啡依赖小鼠和大鼠催促戒断症状的影响。方法:采用剂量递增方式皮下注射酸吗啡,建立吗啡依赖小鼠和大鼠模型,用纳洛酮催瘾。结果:Tet 15,30或60 mg/kg,可明显抑制小鼠催促戒断后的体重下降及一些戒断体征,大鼠给予 Tet 15,30或60 mg/kg 预处理,可抑制1 h 体重下降,明显改善戒断时的行为表现,戒断症状评分随剂量增加而下降。Tet 15 mg/kg 与可乐定0.075 mg/kg 联用,对吗啡依赖小鼠和大鼠催促戒断症状有明显对抗作用。但以上处理对小鼠和大鼠的跳跃反应均无影响。结论:Tet 可缓解吗啡依赖小鼠和大鼠的戒断症状,小剂量 Tet 与可乐定联用可能是一种较好的用药方案。     

A 90 day repeated oral toxicity study on plantamajoside concentrate from Plantago asiatica

Plantago asiatica is distributed widely in East Asia. Since ancient times it has been used as a diuretic to treat acute urinary infections, and as an antiinflammatory, antiasthmatic, antioxidant, antibacterial, antihyperlipidemic and antihepatitis drug. The major compound, plantamajoside from P. asiatica, which is used as a marker compound in chemotaxonomic studies, was reported to have antibacterial activity, inhibition activity against cAMP phosphodiesterase and 5-lipoxygenase and antioxidant activity. However, there are no reports on the safety of plantamajoside. This study assessed the toxic effects of plantamajoside concentrate (PC), the purity of which was above 80%, in rats following administration at dose levels of 0, 500, 1000 and 2000 mg/kg body weight/day for 13 weeks, as recommended by the OECD guidelines. The results showed that there were no differences in body weight, food intake, water consumption, relative organ weight or the hematological and serum biochemical values among the different dosage groups. No death or abnormal clinical signs were observed during the experimental period. Therefore, the results suggested that no observed adverse effect level (NOAEL) of the PC in rats after oral administration is considered to be greater than 2000 mg/kg in rats under the conditions employed in this study.