Glucose-lowering activity of amino acid-N-phosphonic acid oxovanadium complexes and its interaction with DNA

Vanadium has well-documented lowering glucose properties both in vitro and in vivo. The design of new oxovanadium(IV) coordination compounds, intended for use as insulin-enhancing agents in the treatment of diabetes mellitus, can potentially benefit from a synergistic approach, in which the whole complex has more than an additive effect from its component parts. Biological testing with oxovanadium(IV) organic phosphonic acid, for insulin-enhancing potential included acute administration, by oral gavage in streptozotocin (STZ) diabetic rats. The complexes of oxovanadium(IV) amino acid-N-phosphonic acid exhibit higher lowering glucose activity in vivo. The interaction of the complexes of oxovanadium(IV) amino acid-N-phosphonic acid with DNA was investigated by agarose gel electrophoresis. The results indicated that these complexes have strong interaction with DNA.

Inhibition of bromophenols against PTP1B and anti-hyperglycemic effect of Rhodomela confervoides extract in diabetic rats

Protein tyrosine phosphatase 1B (PTP1B) plays an important role as a negative regulator in insulin signaling pathways. PTP1B is an effective target for the treatment of type 2 diabetes mellitus. Four bromophenol derivatives from red algae Rhodomela confervoides, 2,2',3,3'-tetrabromo-4,4',5,5'-tetra-hydroxydiphenyl methane (1), 3-bormo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl) pyrocatechol (2), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (3) and 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-ethyloxy-methyldiphenylmethane (4) showed significant inhibitory activity against PTP1B (IC50 were 2.4, 1.7, 1.5 and 0.84 mu mol/L, respectively) as potential therapeutical agents for the treatment of type 2 diabetes mellitus. The anti-hyperglycemic effects of the ethanol extracts from R. confervoides on streptozotocin-induced diabetes (STZ-diabetes) in male Wistar rats fed with high fat diet were investigated. The STZ-diabetic rats treated with medium-dose and high-dose alga extracts showed remarkable reductions in fasting blood glucose (FBG) as compared with the STZ-diabetic control. The results indicate that the in vivo anti-hyperglycemic activity of the R. confervoides extracts can be partially attributed to the inhibitory actions against PTP1B of the bromophenol derivatives and that may be of clinical importance in improving the management of type 2 diabetes mellitus.

重组人胰岛素样生长因子1对db/db小鼠血糖的影响

下载PDF阅读器目的:研究重组人胰岛素样生长因子1(rhIGF-1)对近似于人类2型糖尿病的db/db小鼠的降血糖作用.方法:正常饲养db/db及同品系的正常小鼠,定期监测血糖和血胰岛素水平.待db/db小鼠表现出明显的高血糖及高胰岛素血症后随机分为4组,每日皮下注射溶媒、胰岛素或不同剂量的rhlGF-1,共2周.首次给药后每30min测定血糖1次,观测不同干预方式的即时降糖效果.再于每次给药前测定血糖,观察2周内的变化趋势.结果:db/db小鼠饲养至8周龄时表现出明显的血糖升高及高胰岛素血症.所用剂量的胰岛素对db/db小鼠未表现出明显的降血糖作用;rhIGF-1特别是高剂量rhIGF-1即时及短期降糖效果均较明显,可有效保护db/db小鼠.结论:rhIGF-1对db/db小鼠有较好的降血糖作用,对伴有明显胰岛素抵抗的糖尿病患者具有临床应用前景.

三种藏药材的化学成分研究

本学位论文报道了西藏产三种藏族传统植物药材的化学成分研究。论文由四章组成，前三章是实验部分，分别报道了尼泊尔黄堇(Corydalis hendersonii Hemsl.)、藏波罗花(Incarvillea younghusbandii Sprague)和全缘叶绿绒蒿(Meconopsis interifolia Franch.)的化学成分研究结果。从这三种青藏高原药用植物中共分离鉴定出33 个化合物，其中1 个是新化合物。第四章概述了罂粟科紫堇属植物的化学和药理研究进展。 第一章为尼泊尔黄堇的化学成分研究。通过正、反相硅胶柱色谱等分离方法从药用植物尼泊尔黄堇的地上部分共分离纯化得到12 个化合物。运用MS、1H-NMR、13C-NMR、DEPT、HMBC、NOESY 等现代波谱学方法将它们的结构鉴定为：刺罂粟碱(1) ， 普托品(2) ， 新那亭(3) ， 斯可任(4) ， tetrahydrothalifendine (5) ，9-methyl-decumbenine C (6)，tetrahydroberberrubine (7)，隐品碱(8)，α-别隐品碱(9)，6,7-methylenedioxy-1(2H)-oxoisoquinolinone (10)，6-丙酮基-5,6 -二氢血根碱(11)和β-谷甾醇(12)。其中化合物6 为新化合物，为首次发现的分子骨架上C-9 位连有甲基的苯肽异喹啉类型生物碱。另外，除化合物1 和2 外，其它9 个生物碱（3～11）均为首次从该种植物中分离得到。同时，我们还对对尼泊尔黄堇中的总生物碱进行了串联质谱分析。 第二章为藏波罗花的化学成分研究。从该药用植物的地上部分共分离得到16个化合物，通过理化常数和波谱数据鉴定为：异佛手柑内酯(1)，6-甲氧基当归素(2)，欧前胡素(3)，花椒毒内酯(4)，珊瑚菜素(5)，水合氧化前胡素(6)，rivulobirin A (7)，齐墩果酸甲酯(8)，咖啡酸甲酯(9)，银桦酸(10)，(D)-boschniakinic acid (11)，对羟基苯甲酸(12) ， tert-O-β-D-glucopyranosyl-(R)-heraclenol (13) ， 5-methoxy-8-O-β-D-glucopyranosyloxypsoralen (14)，前胡苷V(15)和苯乙醇-O-β-D-吡喃葡萄糖-(1→2)-O-β-D-吡喃葡萄糖苷(16)。所有以上化合物均为首次从该种植物中分离得到。另外我们还首次对藏波罗花挥发油的化学成分进行了气相色谱-质谱(GC-MS)联用分析，共鉴定出39 个挥发性成分。 第三章为全缘叶绿绒蒿化学成分的分离鉴定。从传统藏药材全缘叶绿绒蒿地上部分共分离纯化出8 个化合物。通过理化常数和波谱数据将他们的结构分别鉴定为：去甲血根碱(1)，β-谷甾醇(2)，3-羟基-齐墩果烷-12(13)-烯-30-酸(3)，6-丙酮基-5,6-二氢血根碱(4)，木犀草素(5)，胡萝卜苷(6)，quercetin 3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (7)和普托品(8)。其中化合物1，4 和7 为首次从该种药用植物中分离得到。 第四章为综述，总结和归纳了近年来罂粟科紫堇属植物的化学和药理研究进展。 This dissertation consists of four parts. The first, second and third parts report the studies on the chemical constituents from the medicinal plants of Corydalis hendersonii, Incarvillea younghusbandii and Meconopsis interifolia. The forth part reviews the progress of the studies on Corydalis species. The first chapter is about the isolations and identifications of alkalids from the aerial parts of C. hendersonii which is a traditional Tibetan medicine to treat febrifuge, high blood pressure and hepatitis. A new isoquinoline alkaloid, 9-methyl-decumbenine C (6), together with ten known alkaloids, stylopine (1), protopine (2), canadine (3), scoulerine (4), tetrahydrothalifendine (5), tetrahydroberberrubine (7), cryptopine (8), α-allocryptopine (9), 6,7-methylenedioxy-1(2H)-isoquinolinone (10) and 6-acetonyl-5,6-dihydrosanguinarine (11), and β-sitosterol (12) were isolated. Their structures were elucidated by spectroscopic methods. Furthermore, the total alkaloids were analyzed by ESI-MSn. The second chapter is about the isolations and identifications of chemical constituents from the aerial parts of I. younghusbandii. Sixteen compounds were isolated and purified by normal and reversed phase silica gel column chromatography. By spectral analysis, there structures were identified as isobergapten (1), sphondin (2), imperatorin (3), xanthotoxin (4), phellopterin (5), heraclenol (6), rivulobirin A (7), methyl oleanolate (8), methyl caffeate (9), grevillic acid (10), (D)-boschniakinic acid (11), 4-hydroxybenzoic acid (12), tert-O-β-D-glucopyranosyl-(R)-heraclenol (13), 5-methoxy-8-O-β-D-glucopyranosyloxypsoralen (14), decuroside Ⅴ(15), and phenylethyl-O-β-Dglucopyranosyl-(1→2)-β-D-glucopyranoside (16). All of these compounds were isolated from this plant for the first time．By the way, the chemical components of the essential oil from I. younghusbandii were analyzed by GC-MS for the first time. The third chapter is about the the isolations and identifications of the chemical constituents of M. interifolia. Eight compounds were isolated and identified as norsanguinarine (1), β-sitosterol (2), 3-hydroxyolean-12(13)-en-30-oic acid (3), 6-acetonyl-5,6-dihydrosanguinarine (4), luteolin (5), daucosterol (6), quercetin 3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (7) and protopine (8). The compounds 1, 4 and 7 were isolated from this herb for the first time. The last chapter is a review of the research progress of the studies on Corydalis species, which includes the chemical constituents in this genus and their pharmacology.