瑞香科植物的研究Ⅰ:双白瑞香素的NMR测定

双白瑞香素(Daphnoretin)为双香豆素衍生物。近来发现,该化合物对小鼠体内试验有抗癌活性,能抑制艾氏腹水癌,并具有抑制多种酶包括艾氏腹水癌细胞中DNA 合成的能力,因此重新引起关注。双白瑞香素主要存在于瑞香科植物中,豆科和芸香料中亦有分布(见表1)     

瑞香素对小鼠免疫功能的影响

<正> 瑞香素(Daphnetin,Dap)系瑞香科植物黄瑞香(Daphne giralaii Nitsche)中的有效单体,化学结构为7,8-二羟基香豆素.实验证明Dap有扩张冠状血管,增加冠状血流,改善心肌代谢作用,并有抑制实验性关节炎,兴奋垂体—肾上腺皮质系统,抗血栓形成,抑制血小板聚集和降血脂功能.临床上对冠心病心绞痛,血栓闭塞性脉管炎和风湿及     

祖师麻基源及化学成分研究概况

目的对中药祖师麻的基源及化学成分进行综述;方法查阅相关文献。结果祖师麻主要来源于瑞香科瑞香属植物黄瑞香(Daphnegiraldii Nitsche)、凹叶瑞香(D.retusa Hemsl)及唐古特瑞香(D.tangutica Maxim)的干燥根皮及茎皮;祖师麻主要含有香豆素类、二萜类、木质素类、黄酮类、蒽醌类等化合物。结论祖师麻药材来源广泛,其中以黄瑞香最为常用;来源不同的祖师麻药材化学成分也有差别。     

瑞香狼毒提取物对肝癌原位移植瘤小鼠的生命延长作用

目的观察瑞香狼毒提取物对肝癌原位移植瘤小鼠的生命延长作用。方法从山西省吕梁山区采集瑞香狼毒,采用水提醇沉的方法制备药物;建立小鼠肝癌原位移植瘤动物模型,采用灌胃给药方法,观察瑞香狠毒提取物对荷瘤动物的生命延长作用。结果瑞香狼毒提取物高、中、低剂量组小鼠平均生存时间分别为(14.7±1.9)d、(13.0±3.4)d和(16.2±3.4)d,模型对照组小鼠平均生存时间为(12.9±2.0)d,阳性对照组小鼠平均生存时间为(12.7±3.4)d,与模型对照组比较,瑞香狼毒低剂量组生命延长率为25.15%,与模型对照组比较差异有统计学意义(P<0.05)。结论瑞香狼毒提取物在适当剂量下能延长肝癌H22荷瘤小鼠的生存时间,对实验性小鼠肝癌可以起到显著的抑制作用。     

天山假狼毒和瑞香狼毒根中挥发性成分研究

目的用GC-MS法分析比较天山假狼毒和瑞香狼毒根中挥发性成分的异同。方法采用索氏提取法提取天山假狼毒和瑞香狼毒根中的挥发性成分,经GC-MS联用仪对挥发性成分进行分析鉴定,采用色谱峰面积归一化法计算各挥发性成分的含量。结果共鉴定出2种植物根中的113个挥发性成分,其中天山假狼毒81个,瑞香狼毒69个,二者有37个共有成分。相对百分含量较高的成分有:十六酸甲酯(hexadecanoic acid-methyl ester)、9,12-顺式十八碳二烯酸[(Z,Z)-9,12-octadecadienoic acid]、角鲨烯(squalene)、1-庚三醇(1-heptatriacotanol)和异柠檬酸乙酯(ethyl iso-allocholate)。结论天山假狼毒和瑞香狼毒根中的挥发性成分有部分相近,但在含量与其他单一组分组成上存在一定的差异,本研究为天山假狼毒和瑞香狼毒药材的质量控制和进一步研究提供了重要理论依据。     

瑞香狼毒提取物抗实验性癫痫筛选研究

目的　对瑞香狼毒六种提取物 (依次为瑞香狼毒水、生离物、丙酮、石油醚、乙醚、乙醇提取物 )进行药效学及毒性比较研究 ,筛选出一种高效低毒的抗癫痫化合物 ,便于临床前机制探讨。方法　采用动物三种惊厥模型 ,测定瑞香狼毒六种提取物抗实验性癫痫半数有效量 (ED50 )。计算其半数致死量 (L D50 )。结果　瑞香狼毒提取物 ～ ,即丙酮、石油醚、乙醚、乙醇四种提取物对小鼠最大电休克发作实验 (MES)、戊四唑惊厥实验(MET)和电刺激大鼠皮层惊厥阈值 (TL S)模型均具有较强的对抗作用。而其中丙酮提取物毒性较低 ,治疗指数高达 14 .9。结论　瑞香狼毒丙酮提取物是一种抗惊厥作用较强而毒性小的有希望的抗癫痫化合物。     

狼毒的有效成分及其药理活性研究进展

狼毒是毒属植物瑞香科瑞香狼毒 (Stellera chamaejasmeL.)或大戟科狼毒大戟 (Euphorbia fischeriana Stued.)、月腺大戟 (Euphorbia ebracteolata Hayata.)的根 ,有逐水祛痰、散结杀虫之功效 ,为常用中药。近年的研究发现 ,狼毒提取物对肿瘤细胞有较强的抑制活性 ,此外还有抗菌和抗病毒作用 ,是一个理想的天然药物开发品种。1 　 化学成分研究1 .1　瑞香狼毒　六十年代初 ,我国的研究者从瑞香狼毒的根中分离出一种酸性物质 ,定为狼毒素 (chamaejamine) ,后来确定了其双氢双黄酮的结构。目前瑞香狼毒中已知的成分主要有倍半萜内酯、二萜生…     

瑞香素调节Shh/Gli1信号通路对乳腺癌增殖、凋亡和化疗敏感性的影响

目的 探究瑞香素调节音猬因子(Shh)/胶质细胞瘤转录因子1(Gli1)信号通路对乳腺癌增殖、凋亡和化疗敏感性的影响。方法 将人乳腺癌细胞株MDA-MB-231细胞分为对照组、瑞香素组(40μmol/L瑞香素)、GANT61组(10μmol/L GANT61)、瑞香素+GANT61组(40μmol/L瑞香素和10μmol/L GANT61);CCK-8实验检测MDA-MB-231细胞增殖;划痕试验检测MDA-MB-231细胞迁移情况;在上述各分组细胞中加入1 mg/L阿霉素(Dox)处理48 h后CCK-8实验检测细胞化疗敏感性;流式细胞术检测MDA-MB-231细胞凋亡情况;Western blot检测MDA-MB-231细胞Shh/Gli1通路及凋亡相关蛋白表达水平。结果 与0μmol/L比较,随着瑞香素的剂量增加MDA-MB-231细胞存活率显著降低(P<0.05),而与40μmol/L比较,50μmol/L瑞香素处理MDA-MB-231细胞存活率无差异(P>0.05),因此选择40μmol/L瑞香素作为后续实验的干预条件;与对照组比较,瑞香素组和GANT61组OD4...     

瑞香狼毒水提取物对肺腺癌细胞株耐药及凋亡的影响

目的探讨瑞香狼毒水提取物对肺腺癌细胞株A549和耐药细胞株A549/DDP细胞凋亡率及耐药基因表达的影响。方法用不同浓度的瑞香狼毒水提取物、顺铂分别及联合处理人肺腺癌细胞株A549和A549/DDP,用MTT法检测肺癌细胞凋亡率、实时荧光定量PCR检测多药耐药(multidrug resistance protein1,MRP1)基因mRNA水平以及用Westernblot检测多药耐药蛋白1(multidrug resistance protein1,MRP1)的表达水平。结果不同浓度瑞香狼毒水提取物作用相同时间或相同浓度作用不同时间对A549和A549/DDP的细胞抑制率差异有统计学意义(P<0.05);瑞香狼毒处理前后A549/DDP细胞株与A549细胞株相比,对顺铂的敏感性差异有统计学意义(P<0.05);同时两细胞株与瑞香狼毒和顺铂联合孵育后MRP1mRNA水平及MRP1蛋白表达水平差异有统计学意义(P<0.05)。结论瑞香狼毒水提取物有明显抗肿瘤作用,能增强肺癌耐药细胞株对DDP的敏感性,对肺癌耐药具有一定的逆转作用。     

瑞香狼毒中新的双黄酮和活性化合物

目的　研究中药狼毒药材来源之一瑞香狼毒(Stellera chamaejasme L)根的化学成分。方法　用各种柱色谱进行分离纯化,用各种波谱分析方法鉴定其结构。结果　从瑞香狼毒的根中分离并鉴定出3种双黄酮和8种木脂素:瑞香狼毒素A (1)和B (2 ) ,4 ,4″,5 ,5″,7,7″-hexahydroxy-3,3″-biflavanone (3) ,(+) kusunokinin (4) ,lirioresinol-B (5) ,magnoleninC (6) ,(-)- pinoresinol monomethyl ether (7) ,(-) pinoresinol(8) ,(+) matairesinol (9) ,isohinokinin (10 )和(-)-eudesmin (11)。结论　化合物1和2为新化合物,1是已知双黄酮chamaejasmenin C的对映体,4 ,6,8,9,10和11是从本植物中首次分得,7是首次从天然界分得,体外生物测试表明3和8有抗菌活性,1,2 ,9和11有免疫调节活性。     

瑞香素对血清脂质及脂蛋白胆固醇含量的影响

Daphnetin is one of the components of Daphne koreana Nakai and the sample used in the experiment is the synthesized product. The compound was shown to possess obvious effect on lipid and lipoprotein cholesterol contents in the serum of normal and hyperlipidemic mice or rats. When daphnetin was given orally to rats, the serum level of high density lipoprotein cholesterol and the ratio of high density lipoprotein cholesterol to total cholesterol of normal rats were raised, whereas no significant effect on the level of lipid in normal mice was observed. Daphnetin (800 mg/kg, po for 1 week) decreased significantly the total cholesterol content in the serum of yolk(0.5 ml) treated mice. In addition, when daphnetin was given orally at a dosage of 800 mg/kg day for 2 weeks, the serum level of total cholesterol decreased. The sernm concentration of high density lipoprotein cholesterol and the ratio of high density lipoprotein cholesterol to total cholesterol in rats with hyperlipidemia increased significantly.     

Nigella sativa L. oil protects against induced hepatotoxicity and improves serum lipid profile in rats

The effects of 4 weeks oral intake of Nigella sativa L. (NS) oil on some liver function tests and D-galactosamine- or carbon tetrachloride-induced hepatotoxicity were investigated in male albino rats. In another series of experiments, the effect of the oil on serum lipid profile was examined in male spontaneously hypertensive rats of stroke prone strain and Wistar Kyoto rats. The study showed that daily administration of the oil per se (800 mg/kg orally for 4 weeks) did not adversely effect the serum transaminases (ALT and AST), alkaline phosphatase, serum bilirubin or prothrombin activity in normal albino rats. When the oil was given for 4 weeks prior to induction of hepatotoxicity by D-galactosamine or carbon tetrachloride, it was able to give complete protection against d-galactosamine and partial protection against carbon tetrachloride hepatotoxicity. NS oil showed a favourable effect on the serum lipid pattern where the administration of the oil (800 mg/kg orally for 4 weeks) caused a significant decrease in serum total cholesterol, low density lipoprotein, triglycerides and a significant elevation of serum high density lipoprotein level.     

Influence of chrysin on hepatic marker enzymes and lipid profile against d-galactosamine-induced hepatotoxicity rats

Chrysin is a flavonoid that exists in nature and is the major component of some traditional medicinal herbs. We investigated the hepatoprotective and antihyperlipidaemic potential of chrysin against d-galactosamine (a single intraperitoneal injection 400 mg/kg BW) induced hepatotoxicity in male albino Wistar rats. d-GalN rats exhibited an increased hepato and nephro toxicity marker activities aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma glutamyl transpeptidase and total bilirubin level while urea, uric acid and creatinine and lipid profile. It also negatively affected the serum total protein, albumin and A/G ratio. Rats treated with chrysin at different concentrations (25, 50 and 100 mg/kg BW) caused a significant improvement in serum protein level, decreased hepato and nephro toxicity markers. It also decreased the levels of very low density lipoprotein cholesterol and low density lipoprotein cholesterol while high density lipoprotein cholesterol significantly increased. It also decreased the levels of total cholesterol, phospholipids, triglycerides, free fatty acids in the plasma and tissues of liver and kidney. The effect of chrysin (25 mg/kg) is comparable with silymarin, a known hepatoprotective drug. Chrysin thus exhibits hepatoprotective and antihyperlipidaemic activity.     

某些药物对大鼠血浆和肝脏脂蛋白脂酶活性及血浆胆固醇的影响

高浓度极低密度脂蛋白(VLDL)和高浓度低密度脂蛋白(LDL)血症是冠心病的易患因子,脂蛋白脂酶(LPL)可使VLDL转化为LDL,故LPL可能促进动脉粥样斑块的形成。但LPL又可促进高密度脂蛋白(HDL)的生成,而HDL是防止动脉粥样硬化斑块形成的有利因子,故又认为LPL可能有利于防止斑块的生成。由此可见LPL对动脉粥样硬化的影响具有两面性,LPL在脂蛋白代谢中的作用非常复杂。     

Effects of ezetimibe,either alone or in combination with atorvastatin,on serum visfatin levels: a pilot study

Introduction: Ezetimibe inhibits intestinal absorption of cholesterol and lowers circulating low-density lipoprotein cholesterol levels. Visfatin is a novel adipokine, which may be implicated in the atherosclerotic process. Objective: The aim of this study was to explore the possible association between ezetimibe administration and serum visfatin concentrations. Methods: Patients (n = 30) with primary dyslipidemia and another 30 who failed to reach their assigned low-density lipoprotein cholesterol target on atorvastatin therapy (20 mg/day) were included in the study. All participants were given ezetimibe at 10 mg/day for 12 weeks. Results: At baseline the visfatin levels correlated significantly with the total cholesterol (r = 0.61 and p < 0.01) and low-density lipoprotein cholesterol (r = 0.51 and p < 0.01) levels in the statin pretreatment group. Furthermore, in the statin group the post-treatment levels of visfatin and low-density lipoprotein cholesterol were significantly correlated (r = 0.57 and p < 0.01). The serum visfatin concentrations did not change significantly in either the monotherapy or statin pretreatment groups or in subgroups divided according to the baseline lipid variables. In both the ezetimibe monotherapy and ezetimibe plus atorvastatin groups the effect of ezetimibe on the lipid variables depended on the baseline lipid values. The low-density lipoprotein cholesterol:high density lipoprotein cholesterol ratio was consistently improved by ezetimibe in all groups or subgroups. Conclusions: Ezetimibe did not alter serum visfatin concentrations, either when administered as monotherapy or combined with a statin. Future studies investigating the effect of ezetimibe on visfatin levels need to include groups of patients with distinct lipid characteristics.     

某些药物对大鼠血浆和肝脏脂蛋白脂酶活性及血浆胆固醇的影响

Lipoprotein lipase (LPL) is one of the most important factors in lipoprotein metabolism. The plasma and liver LPL activities (indicaded by fatty acid release), the ratio of LPL activity to total lipase activity and theoplasma cholesterol levels in rats treated with drugs were determined so as to study the relationship between LPL and lipoprotein metabolism.Plasma LPL activity is negatively related to the total cholesterol and high density lipoprotein cholesterol levels. As the liver LPL activity, increased, the plasma LPL activity also increased. When rats were treated with insulin, phenytoin or Radix Polygonum multiflorum, the plasma and liver LPL activities and the ratio of LPL activity to total lipase activity increased, whereas the plasma total cholesterol and high density lipoprotein cholesterol levels decreased. No significant effect of phenytoin on the total cholesterol level was observed, When large doses of phenytoin were used, the plasma very low density lipoprotein and low density lipoprotein cholesterol level increased and the ratio of high density lipoprotein cholesterol to total cholesterol decreased.     

糖尿病心肌病68例临床特点分析

目的分析探讨糖尿病心肌病的临床特点。方法选择本院2001年8月～2010年7月治疗的糖尿病患者200例,其中伴有糖尿病心肌病患者108例。将糖尿病心肌病患者随机分为两组：糖尿病合并心肌病组和糖尿病无心肌病组。比较两组的一般特征、心脏超声特点及血脂代谢情况。结果两组在性别、年龄比例方面,差异无统计学意义（P〉0.05）,但是病程差异有统计学意义（P〈0.05）。两组三酰甘油、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇比较,差异有统计学意义（P〈0.05）,但是总胆固醇差异无统计学意义（P〉0.05）。糖尿病心肌病患者左心室舒张功能较对照组减弱,心功能异常（射血分数、每搏量及左心室内径缩短率均减小）。结论糖尿病病程时间的长短以及血清三酰甘油的浓度是糖尿病心肌病发病的危险因素。     

Synthesis and Hypolipidemic Activity of 3-Imino-l-oxoisoindolines in Rodents

A series of substituted 3-imino-l-oxoisoindolines derivatives demonstrated significant hypolipidemic activity, lowering both serum cholesterol and triglycerides levels after 16 days of dosing at 20 mg/kg/ day ip in CF₁ mice. 2-Butyl-3-butylimino-l-oxoisoindoline lowered serum cholesterol levels 52% and serum triglyceride 42%. 2-Pentyl-3-imino-l-oxoisoindoline lowered serum cholesterol levels 42% and serum triglyceride 61%. These derivatives resulted in better activity than the parent compound, 3-imino-1-oxoisoindoline. These studies showed that compounds with N-alkyl substitution of nitrogen atoms in the ring and outside the ring possessed potent hypolipidemic activity at the low dose of 20 mg/kg/day ip in normolipidemic CF₁ mice. Studies with 2-butyl-3-butylimino-l-oxoisoinodine in rats showed that serum cholesterol was reduced 60% and serum triglyceride 43% after 14 days of dosing at 20 mg/kg/day, orally. Treatment with this agent lowered lipid levels in the liver and aorta tissue, with increases in lipid levels in the small intestine tissue. Higher levels of cholesterol and phospholipids were excreted in the feces of treated animals compared to the control. Cholesterol levels of the very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) fractions were reduced, whereas the HDL cholesterol levels were elevated significantly. This ratio of low-density lipoprotein (LDL) cholesterol:HDL cholesterol levels suggests that the agent may be effective in treating hyperlipidemic states in humans.     

吩噻嗪类药物引起精神分裂症患者高甘油三酯异常的机制研究

目的：探讨用吩噻嗪类药物治疗后的慢性精神分裂症患者血高油三酯异常特征的危险因素。方法：采用酶法对１１３例精神分裂症者、２５例脑器质性精神障碍患者和１００例健康人血清甘油三酯（ＴＧ）、高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）、总胆固醇（ＴＣ）的水平进行了对比分析。结果：血高ＴＧ与低ＨＤＬ－Ｃ浓度的变化为精神分裂症症患者最显著的脂质异常特征,其中阴性症状组和脑器质性精神障碍患者ＴＧ含量明显高于阳性症状组（Ｐ〈     

Antihyperglycemic and hypolipidemic activity of methanolic extract of Amaranthus viridis leaves in experimental diabetes

To investigate the antihyperglycemic and hypolipidemic effects of methanolic extract of leaves of Amaranthus viridis (MEAV) in normal and Streptozotocin (STZ) induced diabetic rats. The anti-hyperglycemic and hypolipidemic activity of methanolic extract of leaves of Amaranthus viridis was evaluated by using normal and STZ induced diabetic rats at dose of 200 mg/kg and 400 mg/kg by mouth per day for 21 days. Blood glucose levels and body weight was monitored at specific intervals, and different biochemical parameters, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein were also assessed in the experimental animals. Histology of pancreas was performed. The statistical data indicated a significant increase in the body weight, decrease in the blood glucose, total cholesterol and serum triglycerides after treatment with MEAV. High density lipoprotein (HDL) cholesterol level was significantly increased when treated with extract. Histologically, focal necrosis was observed in the diabetic rat pancreas; however, was less obvious in treated groups. The MEAV has beneficial effects in reducing the elevated blood glucose level and body weight changes, and improves the lipid profile of STZ induced rats.