姜黄素抗肝纤维化的实验研究

目的：探讨姜黄素对四氯化碳（CCl4)中毒性纤维化的治疗作用。方法：复制大鼠CCl4肝纤维化模型，以马洛替酯为阳性对照，采用光镜观察组织学改变，测定血清谷丙氨酸转移酶（ALT），谷草氨酸转移酶（AST），一氧化氮（NO），透明质酸（HA），层粘连蛋白（LN），肝组织羟脯氨酸（Hyp，丙二醛（MDA）以反映肝细胞损伤及肝纤维化的程度。结果：姜黄素能降低实验性肝纤维化大鼠血清中升高的ALT,AST,NO,HA,LN水平和过高的肝组织中Hyp,MDA的含量。病理组织学检查亦表明，姜黄素明显改善实验性肝纤维化。结论：姜黄素可能对实验性肝纤维化具有一定的治疗作用。     

Negative Effects of Curcumin on Liver Injury Induced by Alcohol

Curcumin is known for its antiinflammatory and antifibrotic properties in liver damage. However, the negative effects of curcumin on alcoholic liver damage are seldom reported. In this study, both advantageous and disadvantageous functions of curcumin on alcoholic liver injury were observed. In order to determine the effects of curcumin on liver fibrosis induced by alcohol, 5% ethanol and/or curcumin (1 × 10^–3 or 1 × 10^–4 m ) were injected intravenously in mice. Hematoxylin‐eosin staining was performed to determine the value of liver injury by optical density analyses. Liver histology was evaluated by an experienced hepatopathologist blinded to the type of treatment received by the animals. Ethanol accelerates serum levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), liver injury, production of tumor necrosis factor‐alpha (TNF‐α), transforming growth factor‐beta (TGF‐β) and nuclear factor‐kappa B (NF‐κB) during 5% ethanol‐induced liver injury. 1 × 10^–3 m curcumin accelerates liver injury and liver cellular edema during only 5% ethanol‐induced liver injury evolution, whereas 1 × 10^–4 m curcumin does not lead to (or protect) alcoholic liver injury. Therefore, it is suggested that curcumin may have dual effects on alcoholic liver injury depending on its concentration. Copyright © 2012 John Wiley & Sons, Ltd.     

姜黄素抗博莱霉素诱导大鼠肺纤维化的实验研究

目的：探讨姜黄素对博莱霉素（BLM）致肺纤维化的治疗作用。方法：复制大鼠博莱霉素致肺纤维化模型，采用光镜观察组织学改变，测定肺组织羟脯氨酸（Hyp）、超氧化物歧化酶（SOD）、丙二醛（MDA）以反映肺细胞损伤及肺纤维化的程度。结果：姜黄素能降低实验性肺纤维化大鼠过高的肺组织中Hyp、MDA的含量，提高大鼠体内的SOD的含量。病理组织学检查亦表明，姜黄素明显改善实验性肺纤维化。结论：姜黄素对实验性肺纤维化具有一定的治疗作用。     

Anti-diabetes and hypoglycaemic properties of Hemionitis arifolia (Burm.) Moore in rats

Hemionitis arifolia, a folklore anti-diabetes fern, was evaluated for its hypoglycaemic and anti-diabetic properties using rats. Glucose lowering effect and anti-diabetes activity were studied using glucose tolerance test in normal rats and alloxan diabetic rats, respectively. When different extracts were tested, the ethanol and, to some extent, the water extracts were found to lower the levels of blood glucose in glucose fed rats. The ethanol extract showed optimum activity at 200 mg/kg. The extract exhibited only marginal hypoglycaemic activity in overnight fasted normal rats and it was devoid of conspicuous toxic symptoms in sub-acute toxicity evaluation in mice. When the alcohol extract was fractionated by sequential solvent extraction, the activity was found in ethyl acetate fraction (50 mg/kg). This fraction containing steroids and coumarins showed anti-diabetes activity in alloxan diabetic rats as judged from serum glucose levels, liver glycogen content and body weight. This fraction is an attractive material for further research vis-à-vis drug development.     

Ginkgo biloba extract prevents ethanol induced dyslipidemia

Ginkgo biloba extract (EGB) functions as a natural substantial antioxidant and hypolipidemic. Chronic alcohol abuse leads to sustained dyslipidemia characterized by hyperlipidemia and lipid peroxidation. Thus, the present study investigates the effect of EGB on lipid disorders induced by ethanol in rats. Male Sprague-Dawley rats were fed with ethanol (2.4 g/kg), and pretreated with a daily dose of low or high EGB (48 or 96 mg/kg, respectively). During the experiment, serum was collected on day 30, 60, and 90. Serum lipid profile, including lipid peroxidation, was determined by colorimetric methods. Our data showed that ethanol intake resulted in a time-dependent increase in serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and malondialdehyde (MDA), and a decrease of the ratio of high-density lipoprotein cholesterol (HDL-C) against TC. EGB prophylactic medication (48 and 96 mg/kg), especially at the high dose, significantly increased HDL-C content, and normalized the abnormal lipid profile and peroxidation in comparison to ethanol-fed only rats. These results suggest that ethanol results in time-dependent hypercholesterolemia, hypertriglyceridemia and promotes serum lipid peroxidation. EGB pretreatment prevents hyperlipidemia and ameliorates lipid peroxidation induced by ethanol.     

Neuroprotective role of curcumin from curcuma longa on ethanol-induced brain damage.

In the present study, curcumin from Curcuma longa was screened for neuroprotective activity using ethanol as a model of brain injury. Oral administration of curcumin to rats caused a significant reversal in lipid peroxidation, brain lipids and produced enhancement of glutathione, a non-enzymic antioxidant in ethanol intoxicated rats, revealing that the antioxidative and hypolipidaemic action of curcumin is-responsible for its protective role against ethanol induced brain injury.     

蒙药金色诃子炮制品对α-萘异硫氰酸酯致大鼠肝损伤的保护作用及其急性毒性研究

目的:观察蒙药金色诃子不同炮制品对α-萘异硫氰酸酯致大鼠肝损伤的保护作用及其急性毒性。方法:采用a-萘异硫氰酸酯建立大鼠肝损伤模型,给予不同金色诃子炮制品,观察其降酶保肝作用。采用最大给药量方法进行急性毒性实验。结果:与模型组比较,烘制金色诃子能够明显降低a-萘异硫氰酸酯所致肝损伤大鼠血清AST和ALT水平(P0.05)。急性毒性实验小鼠未见异常反应,烘制金色诃子、煮制金色诃子、金色诃子肉最大给药剂量为临床用药量的500倍,生品最大给药剂量为临床用药量的375倍。结论:烘制金色诃子对a-萘异硫氰酸酯所致急性肝损伤具有降酶保肝作用,毒性较小,较为安全。     

姜黄素对5-Fu化疗大鼠肠黏膜屏障保护作用的实验研究

目的：观察姜黄素在利用5-Fu化疗期间对大鼠肠黏膜屏障的保护功能的研究。方法：健康Wister大鼠60只随机分成Control组（20只）,5-Fu组（20只,5-氟尿嘧啶）,5-Fu＋Cur.组（20只,5-氟尿嘧啶＋姜黄素）,在实验的第2、4、6天监测各组大鼠的体重、内毒素、DAO、D-乳酸水平,第7天处死大鼠后取出大鼠回肠,并在光镜下观察肠黏膜组织结构病理变化。结果：与正常组相比,化疗组的体重明显下降（P〈0.05）;内毒素、血浆DAO、D-乳酸水平明显增高（P〈0.05）;肠组织病理学观察可见：肠黏膜明显萎缩,绒毛脱落,并伴有大量炎性细胞浸润。结论：姜黄素对5-Fu化疗期间肠黏膜屏障具有保护作用。     

A study on the toxicology of Acacia nilotica

The potential toxicity of Acacia nilotica was investigated in rats maintained on 2% and 8% acacia diet for 2 and 4 weeks. A significant reduction in body weight in all acacia-fed groups and a significant decrease in the levels of hemoglobin, serum total protein and total cholesterol in animals fed 8% acacia diet for up to 4 weeks were observed. These effects were, however, reversed one week after treatment termination. No significant changes in serum parameters of hepatic and renal functions, fasting glucose and triglycerides were observed. Further, no deaths among treated animals and no significant histopathological changes in liver sections were noted. It is concluded that A. nilotica, at 2% and 8% levels, has a low toxicity potential.     

姜黄素固体分散体在大鼠体内的药动学研究

 目的以聚乙烯吡咯烷酮(PVP)、聚乙二醇(PEG)为载体,分别制备了姜黄素固体分散体。以姜黄素的普通片剂为参比制剂,研究固体分散体在大鼠体内的药动学过程。方法SD大鼠分别灌胃给予姜黄素固体分散体及姜黄素片剂,采用高效液相色谱法测定姜黄素的血药浓度,使用3P97软件计算药动学参数。结果姜黄素固体分散体在大鼠体内药动学过程符合单室模型,与姜黄素普通片剂相比ρ_max,AUC显著增大,姜黄素-PVP固体分散体相对生物利用度为690%。结论姜黄素-PVP固体分散体能显著提高姜黄素在大鼠体内的生物利用度。     

姜黄素对糖尿病大鼠血抗氧化酶和丙二醛含量的影响

目的:观察姜黄素对糖尿病大鼠血清超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性及丙二醛(MDA)含量的影响.方法:链脲佐菌素(STZ)诱导糖尿病大鼠模型,治疗组灌胃给予姜黄素200mg/kg,为期8周.采血检测血清SOD和CAT活性及MDA含量.结果:糖尿病组大鼠血清SOD和CAT活性显著降低,MDA含量明显增加(均 P<0.01).姜黄素治疗组血清SOD和CAT活性明显高于糖尿病组,MDA含量明显低于糖尿病组.结论:姜黄素能有效改善糖尿病大鼠血清抗氧化酶活性,降低MDA水平.     

罗格列酮对高脂饮食诱导非酒精性脂肪肝大鼠脂肪因子的影响

目的观察罗格列酮对高脂饮食诱导的非酒精性脂肪肝大鼠血清中脂肪因子的影响及肝脏保护作用。方法将40只SD大鼠分为对照组、模型组和治疗组。对照组予基础饲料,其余2组予高脂饲料喂养,其中治疗组从第9周开始予罗格列酮5 mg/(kg.d)灌胃,各组均喂养16周。于16周末处死大鼠,称肝脏及脂肪质量,计算肝指数;肝脏组织制作石蜡切片行HE染色;用ELISA法检测各组大鼠血清中抵抗素、瘦素、脂联素水平。结果模型组与对照组相比,肝指数增高,血清中瘦素及抵抗素水平显著升高,光镜下肝脏出现明显脂肪变性及纤维化;治疗组与模型组比较,肝指数降低,光镜下的肝脏脂肪变性及纤维化明显改善,血清中脂联素水平明显上升;但与对照组比较,肝指数仍然显著升高,肝组织中仍有脂肪变性及纤维化,瘦素及抵抗素水平仍有所升高。结论罗格列酮可以显著改善高脂饮食诱导的肝脏脂肪变性,并且对脂肪因子有显著影响。     

姜黄素结构修饰物调血脂与抗脂质过氧化作用研究

 目的研究姜黄素甲氧基水解及酚羟基酯化后的结构修饰物调血脂、抗脂质过氧化作用和对脂代谢相关酶类活性的影响,初步比较其构效关系,以期寻找到结构比姜黄素更适配的化合物,用于调血脂。方法用盐酸水解姜黄素甲氧基获得姜黄素水解物(HCur);用丁二酸酐酯化姜黄素酚羟基获得姜黄素酯化物(ECur);高脂膳食喂饲Wistar大鼠,建立食饵性高脂血症模型,用姜黄素(curcumin)、HCur和ECur进行实验性治疗,给药3周后处死动物,测定血清和肝脏总胆固醇(total cholester-ol,TC)、甘油三酯(triglyceride,TG)和血清高密度脂蛋白(high density lipoprotein cholesterol,HDL-C)含量,计算低密度脂蛋白(low density lipoprotein cholesterol LDL-C)含量,同时测定肝素化血浆总脂解酶(post heparin total activity,PHTA)、脂蛋白脂酶(lipoprotein lipase,LPL)和肝脂酶(hepatic lipase,HL)的活性及血清丙二醛(malondialdehyde,MDA)含量。结果①姜黄素能降低血清和肝脏TC、TG、LDL-C和MDA含量,升高血清HDL-C含量,提高PHTA活性。②HCur能降低TC、LDL-C、TG和MDA含量,能显著提高PHTA与LPL活性。③ECur仅具降LDL-C作用。结论HCur可降低肝脏和血清脂质及血清MDA含量,尤其能提高TG代谢相关酶活性,而ECur仅能降低LDL-C含量,其他活性均不显著,提示姜黄素结构上的酚羟基在降血脂中起重要作用。     

Preliminary studies on antihepatotoxic effect of Physalis peruviana Linn. (Solanaceae) against carbon tetrachloride induced acute liver injury in rats

Physalis peruviana is a medicinal herb used by Muthuvan tribes and Tamilian native who reside in the shola forest regions of Kerala, India against jaundice. It was evaluated for its antihepatotoxic, phytochemical analysis and the acute toxicity of the most promising extract in rats. Water, ethanol and hexane extracts of Physalis peruviana (500mg/kg body weight) showed antihepatotoxic activities against CCl(4) induced hepatotoxicity. The ethanol and hexane extracts showed moderate activity compared to water extract, which showed activity at a low dose of 125mg/kg. The results were judged from the serum marker enzymes. Histopathological changes induced by CCl(4) were also significantly reduced by the extract. Further, the extract administration to rats resulted in an increase in hepatic GSH and decrease in MDA. Preliminary phytochemical analysis revealed the presence of various components in the crude aqueous extract. The extract was found to be devoid of any conspicuous acute toxicity in rats.     

Effects of Croton cajucara Extract on Serum Lipids of Rats Fed A High Fat Diet

The antihyperlipidaemic property of a hydroalcoholic extract obtained from the leaves of Croton cajucara Benth. (Euphorbiaceae) was studied in rats fed a high fat diet. Ten weeks following daily oral administration of plant extract (200 mg/kg), significant reductions in the serum total cholesterol (Tc), and low-density lipoprotein cholesterol (LDL-c) levels were observed without much change in serum high-density lipoprotein cholesterol (HDL-c) and triglycerides. The data also showed a significant elevation in the HDL-c/Tc ratio in plant extract treated rats compared with the control group. The atherogenic index was significantly decreased by extract treatment. These beneficial effects and the absence of acute toxicity in C. cajucara extract may be of significance in the treatment of atherosclerosis.     

鸡鸣散镇痛抗炎作用及其机理的时间药理学实验研究

目的:观察鸡鸣散(Ji-Ming-San,JMS)对啮齿类动物的毒性及镇痛抗炎作用,探讨其机制及昼夜节律性差异,验证前人关于JMS择时用药的合理性。方法:Bliss法计算JMS半数致死量(LD50)及相同剂量下JMS对小鼠急性死亡率的昼夜差异;热板法、扭体法观察JMS镇痛作用,硝酸还原酶法测定小鼠血清及脑组织一氧化氮(NO)含量及其昼夜差异;耳廓肿胀法和足跖肿胀法观察JMS抗炎作用,紫外分光光度计法测炎症组织前列腺素E2(PGE2)含量及其昼夜差异。结果:JMS对小鼠的急性毒性呈显著的用药时间依赖性,白昼毒性大于夜间;JMS对小鼠模型有良好的镇痛作用,呈昼夜节律性,并与其降低小鼠血清、脑组织NO含量的昼夜差异相吻合;JMS具有良好的抗炎作用,呈昼夜差异性,并与其降低炎性组织中PGE2含量的昼夜差异相吻合。结论:JMS具有良好的镇痛、抗炎作用,并呈昼夜节律性,镇痛作用可能与其降低NO含量有关,抗炎作用可能与其降低PGE2含量有关。     

Protective effect of fenugreek (Trigonella foenum graecum) seeds in experimental ethanol toxicity

The study investigates the effect of aqueous extract of fenugreek seeds (Trigonella foenum graecum) on lipid peroxidation and antioxidant status in experimental ethanol toxicity in rats. The ability of the seed extract to prevent iron-induced lipid peroxidation in vitro was also investigated. Ethanol feeding for 60 days resulted in significant increases in the activities of serum aspartate transaminase, alanine transaminase and alkaline phosphatase. The levels of serum lipid hydroperoxides and thiobarbituric acid reactive substances in liver and brain were also significantly elevated. Significantly lower activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and glutathione reductase were observed in liver and brain accompanied by depletion in glutathione, ascorbic acid and alpha-tocopherol concentrations. Activity of Ca(2+) ATPase in brain was significantly lowered. Simultaneous administration of aqueous extract of fenugreek seeds with ethanol prevented the enzymatic leakage and the rise in lipid peroxidation and enhanced the antioxidant potential. The seeds exhibited appreciable antioxidant property in vitro which was comparable with that of reduced glutathione and alpha-tocopherol. Further, histopathological examination of liver and brain revealed that, aqueous extract of fenugreek seeds could offer a significant protection against ethanol toxicity.     

姜黄素抗肺纤维化大鼠细胞外基质过度形成的实验研究

目的:研究姜黄素抗博莱霉素诱导大鼠肺纤维化细胞外基质过度沉积的作用。方法:SD雄性大鼠144只,分为假手术组,模型组,姜黄素高、中、低剂量组,醋酸泼尼松组,每组24只。除假手术组外其余各组大鼠气管内一次性滴注盐酸博莱霉素,假手术组大鼠气管内一次性滴注等体积的生理盐水。造模后第1天开始给药,持续到处死动物的前一天。姜黄素高,中,低剂量组分别为200,100,50 mg.kg^-1.d^-1,醋酸泼尼松组为0.56 mg.kg^-1.d^-1,假手术组,模型组分别灌服等体积的生理盐水。各组动物于7,14,28 d随机处死8只,分别观察大鼠肺组织羟脯氨酸(HYP)和血清中Ⅲ型胶原,Ⅳ型胶原及层黏连蛋白和透明质酸的含量,同时取肺组织进行HE,Mallory染色。结果:姜黄素可降低肺纤维化大鼠血清Ⅲ,Ⅳ胶原,层黏连蛋白及透明质酸含量,减轻肺组织纤维性增生。结论:可能是通过降低肺纤维化大鼠细胞外基质含量而发挥治疗肺纤维化作用。     

The effect of Malaysian cocoa extract on glucose levels and lipid profiles in diabetic rats

The present study aims to investigate the effect of cocoa extract on serum glucose levels and lipid profiles in streptozotocin-diabetic rats. Cocoa extract (contained 285.6 mg total polyphenol per gram extract) was prepared from fermented and roasted (140 degrees C, 20 min) beans by extracting using 80% ethanol in the ratio of 1-10. The extract of three dosages (1, 2, and 3%) was fed to normal and diabetic rats for a period of 4 weeks. In hyperglycaemic group, cocoa extract (1 and 3%) diets were found to significantly lower (p<0.05) the serum glucose levels compared to the control. Furthermore, supplementation of 1 and 3% cocoa extract had significantly reduced (p<0.05) the level of total cholesterol in diabetic rats. In addition, 1, 2, and 3% cocoa extract diets had significantly lowered (p<0.05) the total triglycerides. Interestingly, this study found that serum HDL-cholesterol had increased significantly (p<0.05) in diabetic rats fed with 2% cocoa extract, while the LDL-cholesterol had decreased significantly (p<0.05) in the 1% treated group. These results indicate that cocoa extract may possess potential hypoglycaemic and hypocholestrolemic effects on serum glucose levels and lipid profiles, respectively. The results also found that the effect of cocoa extract was dose-dependent.     

苗族药了哥王不同提取物对正常大鼠肝毒性的影响

目的:考察了哥王不同提取物对正常大鼠肝毒性的影响,并探讨其作用机制。方法:选用SD大鼠72只,随机分成空白组、乙醇提取物组、石油醚提取物组、乙酸乙酯提取物组、正丁醇提取物组和水部位提取物组,每组12只。不同给药组连续灌胃给药2周,每隔2日称量大鼠体重,于第15天,每组随机取6只,麻醉后腹主动脉取血,离心血液,取血清测定丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),碱性磷酸酶(ALP),总胆红素(T-BIL),总蛋白(TP),白蛋白(ALB),血糖(GLU),总胆固醇(CHOL),肌酐(Cr)。取肝组织,称其质量,计算脏器系数,并留取肝组织作病理学检查。每组余下的6只大鼠于第15天停止给药,正常供给饲料与水,恢复2周,观察大鼠恢复情况,于第28天进行上述相同指标的检测。结果:给药2周后,与空白组比较,乙醇提取物组和乙酸乙酯提取物组大鼠的肝脏系数明显增大(P0.05)。乙醇提取物组血清中ALT,AST,GLB明显升高,白蛋白/球蛋白(A/G),TP和ALB明显降低(P0.05);乙酸乙酯提取物组血清中ALP,T-BIL,GLU明显升高,A/G,TP和ALB明显降低(P0.05);石油醚提取物组血清中AST,AST/ALT,ALP,GLU明显升高,T-BIL,A/G,TP和ALB明显降低(P0.05,P0.01);正丁醇提取物组血清中AST/ALT,T-BIL明显升高,A/G明显降低(P0.05,P0.01);水部位提取物组血清中A/G明显降低(P0.05);乙醇提取物组、乙酸乙酯提取物组和石油醚提取物组大鼠肝组织能观察到不同程度的炎细胞浸润,出现一定的肝细胞脂肪变性和局灶性肝细胞坏死,其他组少见。停药恢复2周后,各组肝脏系数均接近于空白组;各组血清中肝功能生化指标基本恢复到空白组水平;各组大鼠肝组织细胞结构清晰,少见炎细胞浸润,未见脂肪变性和肝细胞坏死。结论:苗族药了哥王乙醇提取物组、乙酸乙酯提取物组对肝损伤较大,具有明显的肝毒性;石油醚提取物组对肝也有一定的损伤,但比乙醇提取物组和乙酸乙酯提取物组损伤程度小;正丁醇提取物组毒性较小,水部位提取物组无毒性;停药2周恢复后,各组大鼠反映肝功能的生化指标基本恢复到空白组水平,大鼠的肝损伤明显的减轻,表明了哥王的肝毒性具有一定的可逆性。