胡椒酸乙二胺的急性毒性实验研究
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摘要
目的:研究胡椒酸乙二胺(PAE)的急性毒性作用及安全性。方法:40只昆明种小鼠随机分成实验组和对照组,各20只,实验组用0.5%羧甲基纤维素钠(CMC-Na)配制的PAE混悬液对小鼠进行灌胃,对照组用0.5%CMC-Na溶液灌胃,采用最大耐受量(MTD)法,给药剂量为5 g/kg,每天1次,连续14 d,观察给药后小鼠有无异常反应及死亡情况,期间记录体重变化,实验结束解剖动物,称量脏器湿重,计算脏器系数。结果:给药后小鼠未出现死亡和毒性反应,解剖肉眼观脏器未见病变,分析比较两组小鼠体重、脏器湿重及脏器系数,差异均无统计学意义(P>0.05)。结论:胡椒酸乙二胺属低毒性化合物。
Objective To study the acute toxicity and safety of the piperic acid ethylenediamine(PAE). Methods 40 Kunming mice were randomly divided into experimental group and control group, with 20 mice in each group. The experimental group was intragastrically administered with PAE suspension formulated with 0.5% Sodium carboxymethyl cellulose(CMC-Na), and the control group was gavaged with 0.5% CMC-Na solution. Use the maximum tolerance method(MTD), the intragastric dose was 5 g/kg, the mice were given by gavage once a day for 14 days, observed any adverse reactions and deaths after the treatment, and the body weight changes were recorded during the experiment. At the end of the experiment dissected the animal, weighed the wet weight of the organ, and calculated the organ coefficient. Results There was no death and toxicity in the mice after administration, and no pathological changes were observed in the naked eye, analysis and comparison of body weight, organ wet weight and organ coefficient of the two groups of mice, the difference was not statistically significant(P>0.05). Conclusion Piperonic acid ethylenediamine is a low toxicity compound.
Objective To study the acute toxicity and safety of the piperic acid ethylenediamine(PAE). Methods 40 Kunming mice were randomly divided into experimental group and control group, with 20 mice in each group. The experimental group was intragastrically administered with PAE suspension formulated with 0.5% Sodium carboxymethyl cellulose(CMC-Na), and the control group was gavaged with 0.5% CMC-Na solution. Use the maximum tolerance method(MTD), the intragastric dose was 5 g/kg, the mice were given by gavage once a day for 14 days, observed any adverse reactions and deaths after the treatment, and the body weight changes were recorded during the experiment. At the end of the experiment dissected the animal, weighed the wet weight of the organ, and calculated the organ coefficient. Results There was no death and toxicity in the mice after administration, and no pathological changes were observed in the naked eye, analysis and comparison of body weight, organ wet weight and organ coefficient of the two groups of mice, the difference was not statistically significant(P>0.05). Conclusion Piperonic acid ethylenediamine is a low toxicity compound.
引文
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[23]中华人民共和国国家卫生和计划生育委员会.食品安全性毒理学评价程序:GB 15193.1-2014[S].北京:中国标准出版社,2014.
[24]孙玉珍,方毅,李书丹,等.红树莓根茎水煎剂对昆明小鼠的急性毒性及安全性实验研究[J].中医药学报,2018,46(3):58-61.
[2]Li M,Shu X,Xu H,et al.Integrative analysis of metabolome and gut microbiota in diet-induced hyperlipidemic rats treated with berberine compounds[J].Journal of Translational Medicine,2016,14(1):237-249.
[3]Sham TT,Chan CO,Wang YH,et al.A Review on the Traditional Chinese Medicinal Herbs and Formulae with Hypolipidemic Effect[J].Biomed Research International,2014(10):1155-1175.
[4]吐尔孙拜克·叶尔达,纳森巴特.胡椒碱合成胡椒酸己二胺的中试放大研究[J].中国石油和化工标准与质量,2014,2(24):64-65.
[5]徐抒,吐尔孙拜克·叶尔达,铁日格力,等.胡椒酸己二胺降血脂及抗氧化作用的实验研究[J].河北医学,2016,22(5):868-870.
[6]阿荣,乔延江,博格日勒图,等.荜茇宁衍生物对高脂血症大鼠调脂作用及其机制的研究[J].安徽医药,2015,19(8):1446-1449.
[7]张桂秋,李丹,杨异卉.胡椒碱衍生物的化学合成及生物活性研究进展[J].中国临床药理学杂志,2017,33(14):1374-1378
[8]李凤奎,王纯耀.实验动物与动物实验方法学[M].郑州:郑州大学出版社,2007.
[9]Zarai Z,Boujelbene E,Ben Salem N,et al.Antioxidant and antimicrobial activities of various solvent extracts,piperine and piperic acid from Piper nigrum[J].LWT-Food Sci Technol,2013(50):634-641.
[10]Majeed M,Prakash L.The medical uses of pepper[J].Int Pepper New,2000(25):23–31.
[11]Jung BS,Shin MK.Encyclopedia of illustrated Korean natural drugs,Araliaceae[J].Seoul:Young Lim Sa,1998:439-443.
[12]Thiel A,Buskens C,WoehBe T,et a1.Black pepper constituent piperine:Genotoxicity studies in vitro and in vivo[J].Food and Chemical Toxicology,2014,66(4):350-357.
[13]Srinivasan K.Black pepper and its pungent principle-piperine:a review of diverse physiological effects[J].Critical Reviews in Food Science & Nutrition,2007,47(8):735-748.
[14]Jwa H,Choi Y,Park UH,et al.Piperine,an LXRalpha antagonist,protects against hepatic steatosis and improves insulin signaling in mice fed a highfat diet[J].Biochem Pharmacol,2012,84(11):1501-1510.
[15]Bai YF ,Xu H.Protective action of piperine against experimental gastric ulcer[J].Acta Pharmacol Sin,2000,21(4):357-359.
[16]Umar S,Golam Sarwar AH,Umar K,et al.Piperine ameliorates oxidative stress,in ammation and histological outcome in collagen induced arthritis[J].Cell Immunol ,2013(284):51-59.
[17]Bae GS,Kim MS,Jung WS,et al.Inhibition of lipopolysaccharide-induced in ammatory responses by piperine.Eur J Pharmacol,2010(642):154-162.
[18]Lucian Hritcu,Jaurès A Noumedem,Oana Cioanca,et al.Anxiolytic and antidepressant profile of the methanolic extract of Piper nigrum fruits in beta-amyloid (1-42) rat model of Alzheimer's disease[J].Behavioral & Brain Functions,2015,11(1):1-13.
[19]Wattanathorn J,Chonpathompikunlert P,Muchimapura S,et al.Piperine,the potential functional food for mood and cognitive disorders[J].Food & Chemical Toxicology An International Journal Published for the British Industrial Biological Research Association,2008,46(9):3106-3110.
[20]Diwan V,Poudyal H,Brown L.Piperine attenuates cardiovascular,liver and metabolic changes in high carbohydrate,higIl fat-fed rats[J].Cell Biochemistry and Biophysics,2013,67(2):297-304.
[21]Choi S,Choi Y,Kim S,et al.Piperine reverses high fat diet-induced hepatic steatosis and insulin resistance in mice[J].Food Chemistry,2013,141(4):3627-3635.
[22]Nogara L,Naber N,Pate E,et al.From the Cover:Piperine’s mitigation of obesity and diabetes can be explained by its up-regulation of the metabolic rate of resting muscle[J].Proc Natl Acad Sci USA,2016,113(46):13009-13014.
[23]中华人民共和国国家卫生和计划生育委员会.食品安全性毒理学评价程序:GB 15193.1-2014[S].北京:中国标准出版社,2014.
[24]孙玉珍,方毅,李书丹,等.红树莓根茎水煎剂对昆明小鼠的急性毒性及安全性实验研究[J].中医药学报,2018,46(3):58-61.