CN100998601A - 一种治疗ⅱ型糖尿病的药物及其评价模型 - Google Patents
一种治疗ⅱ型糖尿病的药物及其评价模型 Download PDFInfo
- Publication number
- CN100998601A CN100998601A CN200610161291.8A CN200610161291A CN100998601A CN 100998601 A CN100998601 A CN 100998601A CN 200610161291 A CN200610161291 A CN 200610161291A CN 100998601 A CN100998601 A CN 100998601A
- Authority
- CN
- China
- Prior art keywords
- medicine
- ucp2
- diabetes
- mengiferin
- tissue
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 24
- 229940079593 drug Drugs 0.000 title abstract description 5
- 206010012601 diabetes mellitus Diseases 0.000 title abstract description 3
- 102000008219 Uncoupling Protein 2 Human genes 0.000 claims description 20
- 108010021111 Uncoupling Protein 2 Proteins 0.000 claims description 20
- 241000699670 Mus sp. Species 0.000 claims description 18
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 15
- 230000014509 gene expression Effects 0.000 claims description 10
- 238000003753 real-time PCR Methods 0.000 claims description 10
- 210000002784 stomach Anatomy 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 238000013210 evaluation model Methods 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 5
- 108090000623 proteins and genes Proteins 0.000 claims description 5
- 241000196324 Embryophyta Species 0.000 claims description 4
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 claims description 4
- 241001093152 Mangifera Species 0.000 claims description 4
- 235000014826 Mangifera indica Nutrition 0.000 claims description 4
- -1 carbon glucoside Chemical class 0.000 claims description 4
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 claims description 4
- ZUJVWTIQQMSESW-UHFFFAOYSA-N 3,4,5-trihydroxy-1h-pyridin-2-one Chemical compound OC1=CNC(=O)C(O)=C1O ZUJVWTIQQMSESW-UHFFFAOYSA-N 0.000 claims description 3
- 244000144725 Amygdalus communis Species 0.000 claims description 3
- 235000011437 Amygdalus communis Nutrition 0.000 claims description 3
- 235000004936 Bromus mango Nutrition 0.000 claims description 3
- 241001071804 Gentianaceae Species 0.000 claims description 3
- 241000196124 Polypodiaceae Species 0.000 claims description 3
- 235000009184 Spondias indica Nutrition 0.000 claims description 3
- 241000159241 Toxicodendron Species 0.000 claims description 3
- 244000044283 Toxicodendron succedaneum Species 0.000 claims description 3
- 235000020224 almond Nutrition 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 229930182478 glucoside Natural products 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 238000003757 reverse transcription PCR Methods 0.000 claims description 3
- 235000013311 vegetables Nutrition 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 2
- 238000002651 drug therapy Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- AEDDIBAIWPIIBD-ZJKJAXBQSA-N mangiferin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=C(OC=2C(=CC(O)=C(O)C=2)C2=O)C2=C1O AEDDIBAIWPIIBD-ZJKJAXBQSA-N 0.000 abstract 2
- YWQSXCGKJDUYTL-UHFFFAOYSA-N Mangiferin Natural products CC(CCC=C(C)C)C1CC(C)C2C3CCC4C(C)(C)CCCC45CC35CCC12C YWQSXCGKJDUYTL-UHFFFAOYSA-N 0.000 abstract 1
- 229940043357 mangiferin Drugs 0.000 abstract 1
- 210000001519 tissue Anatomy 0.000 description 14
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 239000000523 sample Substances 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 101150076688 UCP2 gene Proteins 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 210000004153 islets of langerhan Anatomy 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 230000003914 insulin secretion Effects 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 206010013183 Dislocation of vertebra Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 101150112014 Gapdh gene Proteins 0.000 description 1
- 241001293752 Gentiana manshurica Species 0.000 description 1
- 108020005004 Guide RNA Proteins 0.000 description 1
- 240000007228 Mangifera indica Species 0.000 description 1
- 102000015494 Mitochondrial Uncoupling Proteins Human genes 0.000 description 1
- 108010050258 Mitochondrial Uncoupling Proteins Proteins 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 238000012356 Product development Methods 0.000 description 1
- 241000025505 Pyrrosia Species 0.000 description 1
- 238000001190 Q-PCR Methods 0.000 description 1
- 241000977602 Swertia mussotii Species 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000011697 diabetes animal model Methods 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000010627 oxidative phosphorylation Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
本发明属于生物制药及分子生物学技术领域,所述芒果甙为一种四羟基吡啶的碳糖甙,在多种植物中存在。C57/BL6小鼠灌胃给予芒果甙,可使小鼠肾组织UCP2(Uncoupling Protein 2,解偶联蛋白2)基因表达水平显著下调。本发明阐明了芒果甙可以抑制肾组织中UCP2基因的表达,可在制备预防和治疗II型糖尿病药物中应用,并提出了一个治疗II型糖尿病药物的评价模型。
Description
一、技术领域
本发明属于生物制药及分子生物学技术领域。
二、背景技术
胰岛细胞功能异常和胰岛素抵抗常导致II型糖尿病的发生。胰岛细胞功能异常是一种复杂的现象,包括对葡萄糖感应的丧失,导致GSIS(glucose-stimulated insulin secretion)损害等。
UCP2(Uncoupling Protein2,解偶联蛋白2)是解偶联蛋白家族的新成员,为一种位于线粒体内膜上的阳离子载体蛋白。它可以引起质子的渗漏,使氧化磷酸化解偶联,ATP合成减少,能量以热的形式散失。UCP2是胰岛素分泌的负调节分子。首先,它介导了线粒体内膜的质子渗漏,这已被一系列的研究所证明,这些研究的对象涵盖了原脂质体、线粒体以及完整细胞(Proc.Natl.Acad.Sci.,99:118-122,2002)。在胰岛β细胞中,UCP2介导的质子渗漏使得糖生成的ATP数量降低,从而负调节GSIS。ob/ob小鼠是肥胖导致的糖尿病动物模型,在该小鼠胰岛中,UCP2表达显著升高。另外,高血糖也能导致胰岛内UCP2表达升高。更重要的是,在ob/ob小鼠中敲除UCP2,胰岛素分泌的第一相能得到恢复,并且血清中胰岛素含量升高,高血糖症状也得到改善(Cell,105:745-755,2001)。这些结果充分说明,UCP2在高血糖以及肥胖导致的胰岛功能异常中发挥了重要作用。因此,有效抑制UCP2基因在胰岛等组织中的表达对治疗II型糖尿病有较大意义,具有该作用特点的药物可应用于II型糖尿病的治疗。
芒果甙是一种四羟基吡啶的碳糖甙,属双苯吡酮类化合物。在漆树芒果树(Mangifera indica),扁桃树(Mangifera persiciformis)的叶、果实、树皮,龙胆科植物东北龙胆(Gentiana manshurica kitag)、川西瘴芽菜(Swertia mussotii franch),百合科植物知母(Anmarrhena asphodeloides bge.),水龙骨科植物光石韦(Pyrrosia ca/vata(Bak)china)等多种植物中存在。药理学研究表明,芒果甙可降低糖尿病模型小鼠(KK-Ay mice)的血糖并提高其胰岛素耐量,对正常小鼠无明显作用(1.BiolPharm Bull,21(12):1389-90,1998;2.Phytomedicine,8(2):85-7,2001)。
三、发明内容
本发明需要解决的问题是采用现代细胞生物学和分子生物学实验方法,研究芒果甙作为一种治疗II型糖尿病的药物的应用及其分子作用机制,提出UCP2很有可能是中医寒热理论的一个重要效应分子,是芒果甙作用的靶点。同时,建立一种评价治疗II型糖尿病药物的模型。
本发明的技术方案如下:
1.本发明采用芒果甙进行体内试验。芒果甙是从漆树芒果树、扁桃树、龙胆科植物东北龙胆、川西瘴芽菜、百合科植物知母和水龙骨科植物光石韦中提取的一种四羟基吡啶的碳糖甙,其结构式为:
(1)动物模型、给药方法及组织的分离提取:
雄性正常C57/B6小鼠,随机分为对照组和给药组,每组10只。给药组分两次灌胃给予本发明药物(芒果甙100mg/kg),两次灌药间隔8h,第二次灌药6h后处死动物。对照组正常喂食,给予生理盐水。取小鼠肾组织,立即放入液氮或Trizol中,以防止RNA降解。
(2)组织RNA的提取、RT-PCR和real-time PCR:
按RNA提取试剂盒操作,从组织中提取总RNA,然后将RNA反转录成cDNA。PCR(使用半定量PCR引物)、琼脂糖凝胶电泳表明,样品中无基因组DNA污染(图1)。然后用cDNA样品进行Q-PCR(使用定量PCR引物、Taqman探针),比较对照组和给药组肾组织中UCP2基因表达(其中具体分子生物学操作参照《分子克隆实验指南第三版上册》,2002,科学出版社)。半定量和定量PCR均采用GAPDH作为内参。
结果表明,本发明药物可显著降低肾组织UCP2基因表达水平(p<0.05),给药组的UCP2mRNA水平降低约40%(图2),提示芒果甙可抑制小鼠肾脏中UCP2表达。
本发明研究证明,芒果甙可降低小鼠肾组织中UCP2基因表达水平,因而可以改善胰岛细胞的功能和胰岛素分泌,可制备成预防和治疗II型糖尿病的药物。
2.模型评价:
本发明研究提出了一种治疗II型糖尿病药物的评价模型,用待测药物芒果甙灌胃给予C57/BL6小鼠,然后以UCP2为靶点,以定量PCR手段来测量组织中UCP2基因的表达水平。此模型优点在于其采用分子生物学手段,从mRNA水平上用定量的方法来判断药物的有效性,直接从分子水平揭示药物的作用靶点,较普通的定性的生理学方法更深入、更准确,对药物药效和毒性的综合评价提供了一个有益线索。但其成本比普通的生理学方法高,不适宜用于高通量筛选药物。本发明可将体内试验改成体外实验,用成熟的细胞系代替动物作为试验对象即可大大降低试验成本,用于大批量药物筛选。
本发明与现有技术相比,其有益效果在于为中医药治疗II型糖尿病提供了现代分子生物学的评价模型,揭示了一些以芒果甙为有效成分的中药治疗II型糖尿病的作用靶点,证明芒果甙可作为一种治疗II型糖尿病的药物。
四、附图说明
图1为小鼠肾组织普通PCR电泳结果图。
249bp处是小鼠UCP2基因的条带。493bp处是小鼠GAPDH基因(作为内参)的条带;从右向左1~4条带为对照组,5~8为给药组。
图2为UCP2在C57/B6小鼠肾脏中的表达量平均值(定量PCR结果)。
Control为对照组,灌胃生理盐水(0.6ml/20g),MF为给药组,灌胃给予芒果甙(100mg/kg)。注:与对照组比较p<0.05。
五、具体实施方式
下面结合具体实施例对本发明做进一步的阐述,但不对其有任何限制。
材料与来源:
试剂:Trizol购自Invitrogen公司;逆转录酶和Taq酶购于大连宝生物工程有限公司。本发明中芒果甙购于广西昌洲天然产物开发有限公司。
手术器械:剪刀、弯头小镊等购自江苏思来科技有限公司。
其它器材:Heidolph DIAX900匀浆器;ABI Prism7000Sequence DetectionSystem PCR仪;C57BL/6小鼠购于南京大学模式动物中心
实验用小鼠为SPF级的野生型雄性小鼠,品系C57/BL6,9周龄,饲养于南京市鼓楼医院动物实验中心。
实施例是将芒果甙用生理盐水配制成一定浓度的混悬液,给药体积为30ml/kg,对照组灌服等体积的生理盐水。
实施例1动物模型、给药方法及组织的分离提取
雄性C57/B6小鼠(9周大)正常饲养一周后,随机分为对照组和给药组,每组10只小鼠。给药组于第1天晚上,灌胃给予芒果甙(100mg/kg),8h后第二次灌胃给予同样剂量的芒果甙,6h后颈椎脱臼法处死动物。对照组正常喂食,给予生理盐水。
在冰台上取小鼠肾组织,生理盐水漂洗干净,立即放于冻存管中,于液氮中保存备用。
实施例2组织RNA的提取、RT-PCR和real-time PCR
取适量组织(约100mg)加1ml Trizol于Heidolph DIAX900组织匀浆器将组织充分匀浆(3档120秒),将匀浆液转入洁净的1.5ml离心管中,加入200μl氯仿,13200rpm离心10分钟,小心吸取上清至另一洁净的1.5ml离心管中,加入等体积的异丙醇,13200rpm离心10分钟,弃上清,用75%乙醇洗涤沉淀,室温干燥。然后用20μl DEPC水溶解该沉淀,紫外分光法检测总RNA的浓度和纯度。
2μgRNA用于逆转录,反应体系为20μl,含2μg RNA,1mM dNTP,RNA酶抑制剂1U/μl,Olig(dT)18引物2.5 pmol/μl,AMV逆转录酶0.5U/μl,轻轻混匀,42℃孵育1小时,冰上放置2min。所得cDNA可用于real-time PCR。
real-time PCR为20μl反应体系,分别含0.5μl(检测GAPDH)和15μl(检测UCP2)cDNA,2mM MgCl2,0.2mM dNTP,各1pmol/μl上、下游引物及相应的探针,0.025U/μl Taq酶,混匀。PCR反应条件:95℃5分钟,95℃30秒,60℃60秒(40个循环)72℃延伸3分钟。
目的基因UCP2和内参GAPDH的引物序列:
普通PCR引物序列:
UCP2-sense:5’-GCTGGTGGTGGTCGGAGAT-3’
UCP2-antisense:5’-GGGAGGCGATGACGGTGGT-3’
GAPDH-sense:5’-GCAGTGGCAAAGTGGAGATT-3’
GAPDH-antisense:5’-GTCTTCTGGGTGGCAGTGAT-3’
定量PCR引物序列:
UCP2-sense:5’-CCAATGTTGCCCGWAATG-3’
UCP2-antisense:5’-TGAGGTTGGCTTTCAGGAG-3’
GAPDH-sense:5’-TGTGTCCGTCGTGGATCTGA-3’
GAPDH-antisense:5’-CCTGCTTCACCACCTTCTTGA-3’
定量PCR探针序列:
UCP2-probe:5’-CTGGTGACCTATGACCTCATCAAAG-3’
GAPDH-probe:5’-CCGCCTGGAGAAACCTGCCAA-3’
结果用ABI Prism7000SDS Software分析,见图2。
Claims (4)
2.根据利用权利要求1所述的芒果甙作为待测药物治疗II型糖尿病的评价模型,其特征是用待测药物芒果甙灌胃给予C57/BL6小鼠后,以UCP2为靶点,以定量PCR手段来测量组织中UCP2基因的表达水平。
3.根据利用权利要求2所述的治疗II型糖尿病的评价模型,其特征是:
(1)用雄性正常C57/B6小鼠作为实验对象,两次灌胃6小时后处死取组织,放入液氮或Trizol中保存;
(2)提取组织RNA,用RT-PCR和real-time PCR的方法,以UCP2为目标基因,GAPDH为内参,测量组织中UCP2基因的表达水平,判断药物可否预防和治疗II型糖尿病。
4.根据利用权利要求1所述的芒果甙在制备预防和治疗II型糖尿病药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200610161291.8A CN100998601A (zh) | 2006-12-20 | 2006-12-20 | 一种治疗ⅱ型糖尿病的药物及其评价模型 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200610161291.8A CN100998601A (zh) | 2006-12-20 | 2006-12-20 | 一种治疗ⅱ型糖尿病的药物及其评价模型 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN100998601A true CN100998601A (zh) | 2007-07-18 |
Family
ID=38257472
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200610161291.8A Pending CN100998601A (zh) | 2006-12-20 | 2006-12-20 | 一种治疗ⅱ型糖尿病的药物及其评价模型 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN100998601A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011044751A1 (zh) * | 2009-10-16 | 2011-04-21 | 天津中医药大学 | 芒果叶苷及其制备方法与应用 |
-
2006
- 2006-12-20 CN CN200610161291.8A patent/CN100998601A/zh active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011044751A1 (zh) * | 2009-10-16 | 2011-04-21 | 天津中医药大学 | 芒果叶苷及其制备方法与应用 |
US8829167B2 (en) | 2009-10-16 | 2014-09-09 | Tianjin University Of Traditional Chinese Medicine | Foliamangiferosides, preparation method and use thereof |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Obatomi et al. | Anti-diabetic properties of the African mistletoe in streptozotocin-induced diabetic rats | |
CN101631544B (zh) | 作为治疗剂的色酮 | |
US20060165721A1 (en) | Cinnamomi and poria composition, method to prepare same and uses thereof | |
Wang et al. | Steaming changes the composition of saponins of Panax notoginseng (Burk.) FH Chen that function in treatment of hyperlipidemia and obesity | |
CN112645808A (zh) | 一种高良姜中分离的5-羟基-1,7-二苯基-3-庚酮及其应用 | |
Sun et al. | Dissection of the role of paeoniflorin in the traditional Chinese medicinal formula Si-Ni-San against contact dermatitis in mice | |
Aja et al. | Evaluation of anti-diabetic effect and liver enzymes activity of ethanol extract of Pterocarpus santalinoides in alloxan induced diabetic albino rats | |
Sulistyowati et al. | Systematic literature review: potential anti hyperglycemia Imperata cylindrica | |
Lu et al. | Preclinical studies of licorice in ulcerative colitis: a systematic review with meta-analysis and network pharmacology | |
Tahsin et al. | In vivo and In silico assessment of diabetes ameliorating potentiality and safety profile of Gynura procumbens leaves | |
CN101284001B (zh) | 芒果甙元在制备预防和治疗ii型糖尿病药物中的应用 | |
CN101879156A (zh) | 一种药物组合物及其应用 | |
Su et al. | Evaluation of the Chinese medicinal herb, Graptopetalum paraguayense, as a therapeutic treatment for liver damage in rat models | |
CN112552155A (zh) | 一种高良姜中分离的1,7-二苯基-4-庚烯-3-酮及其应用 | |
CN100998601A (zh) | 一种治疗ⅱ型糖尿病的药物及其评价模型 | |
CN111317791A (zh) | 一种清热通淋片及其制备方法 | |
Szulc et al. | Combined effects of methyldopa and baicalein or Scutellaria baicalensis roots extract on blood pressure, heart rate, and expression of inflammatory and vascular disease-related factors in spontaneously hypertensive pregnant rats | |
Li et al. | Xiangshao Granules reduce the aggressive behavior and hippocampal injury of premenstrual irritability in rats by regulating JIK/JNK/p38 signal pathway | |
Kolawole | The effect of Bridelia ferruginea and Senna alata on plasma glucose concentration in normoglycemic and glucose induced hyperglycemic rats | |
CN103830288B (zh) | 赛葵总黄酮提取物及其制备方法和用途 | |
CN102526227A (zh) | 藏边大黄提取物在制备防治脂肪性肝病药物中的应用 | |
CN112898143A (zh) | 高良姜中分离5-羟基-7-(4-羟基-3-甲氧基苯基)1-苯基-3-庚酮及其应用 | |
CN105920071B (zh) | 一种具有明确谱效关系的红花提取物的用途 | |
Liu et al. | Changtai granule, a traditional Chinese drug, protects hapten-induced colitis by attenuating inflammatory and immune dysfunctions | |
CN104435077B (zh) | 一种狗蚁草乙酸乙酯提取物的制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |