In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre

OBJECTIVE: Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fi bre of Dwarf Red variety of Cocos nucifera were evaluated in this study.METHODS: The dried powdered husk fi bre was exhaustively extracted with hexane, ethyl acetate and methanol successively and the methanolic extract was screened for fl avonoids, phenolics, tannins, alkaloids, steroids, triterpenes, phlobatannins, anthraquinones and glycosides. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei NK65-infected mice, to which the extract was administered at doses of 31.25, 62.5, 125, 250 and 500 mg/kg body weight(BW). Toxicity of the extract was evaluated in rats using selected hematological parameters and organ function indices after orally administering doses of 25, 50 and 100 mg/kg BW for 14 d.RESULTS: Phytochemical analysis revealed the presence of alkaloids, tannins, phenolics, saponins, glycosides, steroids and anthraquinones in the extract. Moreover, the extract reduced parasitemia by 39.2% and 45.8% at doses of 250 and 500 mg/kg BW respectively on day 8 post-inoculation. Various hematological parameters evaluated were not significantly altered(P0.05) at all doses of the extract, except red blood cell count which was signifi cantly elevated(P0.05) at 100 mg/kg BW. The extract significantly increased(P0.05) urea, creatinine, cholesterol, high-density lipoprotein-cholesterol and bilirubin concentrations in the serum as well as atherogenic index, while it reduced albumin concentration significantly(P0.05) at higher doses compared to the controls. Alanine aminotransferase activity was reduced in the liver and heart signifi cantly(P0.05) but was increased in the serum signifi cantly(P0.05) at higher doses of the extract compared to the controls.CONCLUSION: The results suggest that methanolic extract of the Dwarf red variety has partial antimalarial activity at higher doses, but is capable of impairing normal kidney and liver function as well as predisposing subjects to cardiovascular diseases.     

半夏泻心汤及其类方不同配伍对正常大鼠胃液成分的影响

目的为类方的配伍研究提供可参考的试验设计方法.方法用均匀设计法对半夏泻心汤及其类方进行组方药量变化研究,以胃液分析为药理学指标,对所得的药理实验数据进行逐步回归分析.结果在半夏泻心汤、甘草泻心汤方中,各药味对胃液成分的影响其变化趋势类似,但影响程度不尽相同,生姜泻心汤与其他两方出入较大.不同药味之间存在交互作用.结论本方法对类方配伍研究有一定参考价值.     

肾络通对肾间质纤维化实验大鼠病理及基质金属蛋白酶系统的影响

目的观察肾络通对实验大鼠肾间质纤维化的拮抗作用并探讨其作用机理。方法用单侧输尿管结扎方法复制大鼠肾梗阻模型,将其随机分为缬沙坦组、肾络通组、肾络通加缬沙坦组与模型组,并设假手术组。观察梗阻侧肾脏组织形态学改变、基质金属蛋白酶-1(MMP-1)及其基质金属蛋白酶抑制剂-1(TIMP-1)在蛋白及基因水平的表达并与假手术组比较。结果模型组及各治疗组与假手术组比较均呈现程度不同的病理损害,MMP-1、TIMP-1表达均有显著增高(P<0.05),且TIMP-1表达明显高于MMP-1表达。各治疗组与模型组比较,MMP-1表达无明显差异(P>0.05),TIMP-1表达却明显减少(P<0.05)。治疗各组间比较,TIMP-1表达肾络通加缬沙坦组明显低于缬沙坦组(P<0.05),其他组间均无明显差异(P>0.05)。结论输尿管梗阻后肾组织呈现程度不同的病理损害,可能与MMP-1/TIMP-1表达明显失衡有关。肾络通及缬沙坦对其有一定的抑制作用,且肾络通与缬沙坦联合用药,其作用比单一用药更强。     

丹栀逍遥散对D-半乳糖拟老年性痴呆大鼠脑病理学变化的影响

目的观察丹栀逍遥散对D-半乳糖致拟老年性痴呆模型大鼠病理变化的影响。方法大鼠皮下注射D-半乳糖150 mg/(kg.d),49 d造模,以安理申0.54 mg/(kg.d)为对照,用丹栀逍遥散12.64 g/(kg.d)灌胃防治。第50天取大鼠大脑,HE染色光镜观察组织变化,铅铀染色电镜观察超微病变。结果光镜下,丹栀逍遥散减轻造模大鼠大脑的神经细胞损伤、胶质细胞增生、血管壁扭曲增厚。电镜下,丹栀逍遥散使造模大鼠神经细胞突起病变明显好转,脑血管内皮损伤减轻、基底膜完整、胶质细胞足突规则。结论丹栀逍遥散可减轻脑病理变化,是其防治老年性痴呆的形态学依据。     

Enhancing excitability of dopamine neurons promotes motivational behaviour through increased action initiation

Motivational deficits are a key symptom in multiple psychiatric disorders, including major depressive disorder, schizophrenia and addiction. A likely neural substrate for these motivational deficits is the brain dopamine (DA) system. In particular, DA signalling in the nucleus accumbens, which originates from DA neurons in the ventral tegmental area (VTA), has been identified as a crucial substrate for effort-related and activational aspects of motivation. Unravelling how VTA DA neuronal activity relates to motivational behaviours is required to understand how motivational deficits in psychiatry can be specifically targeted. In this study, we therefore used designer receptors exclusively activated by designer drugs (DREADD) in TH:Cre rats, in order to determine the effects of chemogenetic DA neuron activation on different aspects of motivational behaviour. We found that chemogenetic activation of DA neurons in the VTA, but not substantia nigra, significantly increased responding for sucrose under a progressive ratio schedule of reinforcement. More specifically, high effort exertion was characterized by increased initiations of reward-seeking actions. This effect was dependent on effort requirements and instrumental contingencies, but was not affected by sucrose pre-feeding. Together, these findings indicate that VTA DA neuronal activation drives motivational behaviour by facilitating action initiation. With this study, we show that enhancing excitability of VTA DA neurons is a viable strategy to improve motivational behaviour.     

Gastroprotective effects of amifostine in rats treated by T-2 toxin

Cytoprotector amifostine (AMI) was given in a dose of 50, 100 or 150?mg/kg ip in rats treated with several highly toxic doses of T-2 toxin. The best survival rate (24?h and 7?days after treatment) was obtained with AMI50 (50?mg/kg ip). After T-2 intoxication, a peak in the mean number of gastric lesions (petechiae and ulcerations) was reached on the third day (26.40?±?6.24). Administration of AMI50 reduced, almost completely, the total number of gastric lesions in rats acutely poisoned by 0.5 LD₅₀ T-2 (1.5?mg/kg sc), starting with day 1 after intoxication (5.60?±?3.42).     

阿霉素肾病大鼠podocin mRNA和蛋白的表达

目的观察阿霉素肾病大鼠肾小球上皮细胞足突蛋白podocin mRNA和蛋白的表达。方法肾病组予阿霉素5mg/kg尾静脉注射一次,正常对照组予等量生理盐水尾静脉注射,注射后2周24h尿蛋白定量>30mg为肾病模型成立。观察4周后留24h尿行蛋白定量及血生化检查,并应用半定量RT-PCR和印迹法(Western blotting)测定podocinmRNA和蛋白质的表达。结果正常对照组大鼠podocin蛋白表达的相对量是5·26±1·19,而肾病组大鼠podocin蛋白基本不表达;正常对照组、肾病组podocin分子mRNA的相对值分别为1·06±0·19、1·96±0·98,肾病组大鼠podocinmRNA的表达与正常对照组相比显著上调(P<0·05)。结论阿霉素肾病大鼠蛋白尿的产生可能与podocin蛋白表达的减少有关。     

饲喂乳源免疫调节肽对大鼠生长和免疫的影响

目的探讨乳源免疫调节肽(PGPIPN)对大鼠生长和免疫的影响。方法取42只40日龄的SD大鼠(♀♂各半)随机分为两个实验组和一个对照组(每组14只且♀♂相等,分开饲养)。预饲1周后,实验组Ⅰ和Ⅱ分别被灌喂2.5×10-3g/L和2.5×10-2g/L免疫调节肽,对照组灌喂生理盐水,记录大鼠日采食量和体重。饲养1个月后检测对照组和实验组大鼠淋巴细胞转化、红细胞免疫、巨噬细胞吞噬、日采食量和体重等差别。结果乳源免疫调节肽对大鼠腹腔巨噬细胞吞噬和红细胞免疫有显著促进功能(P<0.05);而对淋巴细胞转化作用有增长的趋势,但未达到显著水平(P>0.05)。与对照组相比,实验组Ⅱ的大鼠日采食量显著地增加(P<0.05),♀♂大鼠分别提高了10.95%和8.03%;增重率有提高的趋势,♀♂大鼠增重率分别提高了5.13%和7.10%,但均未达显著水平(P>0.05)。实验组Ⅰ的大鼠,其日采食量和增重与对照组相比均变化不大。结论乳源免疫调节肽能促进机体的免疫功能,提高其免疫力;增加日采食量。     

Effect of bosentan on leptin and endothelin‐1 concentration in plasma and brain after cardiac arrest in rats

In previous studies, bosentan was found to decrease plasma leptin concentrations after myocardial infarction (MI) in rats and had decreased mortality. The present study was undertaken to examine the effect of bosentan on leptin and endothelin‐1 (ET‐1) concentrations in plasma and ET‐1 concentrations in the hippocampus after cardiac arrest (CA) in rats. Studies were performed in 72 rats divided into treated and untreated animals in the following experimental groups: control, 3 min, 10 min, 1 h, 24 h, and 7 days after CA. Bosentan was given daily 2 h before CA or decapitation, 7 days, by gavage at a dose of 100 mg/kg. Plasma leptin concentration decreased in the early period after CA, and being elevated in 24 h, normalized 1 week later. Bosentan kept plasma leptin concentration at the control level in the postischemic period. Plasma ET‐1 concentration significantly increased during the postischemic period. Bosentan produced the elevation of plasma ET‐1 concentration in the preischemic period and kept the level of ET‐1 at control values after CA. Concentration of ET‐1 in the hippocampus was significantly lower 24 h after CA and was elevated after 1 week. The most dramatic effect of bosentan on ET‐1 concentration was in the hippocampus, where it significantly decreased during the entire postischemic recovery period. We postulate an important effect of bosentan on concentration of ET‐1 and leptin in plasma and ET‐1 in the brain after global cerebral ischemia caused by CA. Drug Dev Res 64:137–144, 2005. © 2005 Wiley‐Liss, Inc.     

大鼠肝再生过程中增殖细胞核抗原的表达

目的:探讨大鼠肝再生过程中肝细胞增殖细胞核抗原(PCNA)表达的变化. 方法:建立肝切除动物模型,用免疫组织化学法、图像分析仪检测肝细胞PCNA的表达. 结果:PCNA强阳性肝细胞数及其总灰度值在肝大部切除后24 h明显增高,肝细胞阳性表达率在48 h达到峰值,至120 h趋于正常水平.结论:PCNA强阳性肝细胞呈规律性变化,提示残余肝可再生.