羌活中的香豆素类成分及其抑制脂多糖诱导的RAW 264.7细胞NO生成活性的研究

目的研究羌活Notopterygium incisum的香豆素类成分及其抗炎活性。方法采用硅胶、HPLC等柱色谱方法进行分离纯化,通过质谱、核磁共振波谱数据鉴定化合物的结构;采用脂多糖(LPS)诱导的小鼠巨噬细胞RAW 264.7炎症反应模型,考察羌活中香豆素类成分对炎症反应模型一氧化氮(NO)生成的影响。结果从羌活甲醇提取物分离得到24个香豆素类化合物,分别鉴定为异欧前胡素(1)、川白芷素(2)、补骨脂素(3)、香柑内酯(4)、茵陈素(5)、欧芹酚(6)、5-去氢羌活醇(7)、环氧脱水羌活醇(8)、7″-O-甲基异羌活醇(9)、佛手柑素(10)、7-异戊烯氧基-6-甲氧基-香豆素(11)、栓翅芹烯醇(12)、羌活醇(13)、去甲呋喃羽叶芸香素(14)、异羌活醇(15)、蛇床夫内酯(16)、6-异戊烯氧基伞形花内酯(17)、紫花前胡苷元(18)、异虎耳草素(19)、紫花前胡苷(20)、前胡苷V(21)、前胡苷I(22)、印枳苷元-11-O-β-D-吡喃葡萄糖基-(1→6)-β-D-吡喃葡萄糖苷(23)、羌活苷(24)。化合物7～10、13和15抑制LPS诱导的RAW 264.7细胞NO生成活性最强,最大半数抑制浓度(IC_(50))值为8.50～35.12μmol/L。结论化合物7为新的天然产物,化合物17为首次从羌活中分离得到;C-5位上具有多烯烃结构的香豆素抑制LPS诱导的RAW 264.7细胞NO生成活性较强。     

北沙参化学成分与药理活性研究进展

北沙参为临床常用中药,也可食用。其化学成分主要为香豆素、木脂素、聚炔等类成分。现代药理研究表明,北沙参具有免疫调节、抗肿瘤、抗炎、抗氧化、保肝等方面的活性。本研究在对国内外有关北沙参的文献资料系统整理以及市场产地调研基础上,对其化学成分和药理活性进行总结,以期为北沙参的质量评价、规范化种植以及中蒙医临床使用提供可靠依据。     

HPLC同时测定化妆品中22种香豆素类化合物及质谱确证

目的 建立同时测定化妆品中22种香豆素类化合物的HPLC及液相色谱-串联质谱验证方法。方法 采用Agilent Eclipse XDB-Phenyl色谱柱(150 mm×4.6 mm,3.5μm),流动相为乙腈-0.1%磷酸,梯度洗脱,流速为1.0 mL·min^–1,柱温为35℃,检测波长分别为227,310 nm。以HPLC结果进行定性筛查,并采用标准曲线法定量,以液相色谱-串联质谱法的结果进行确证。结果 22种香豆素类化合物的线性范围为0.1～10 mg·L^–1,相关系数均>0.999 3,方法检出浓度为0.1～1.5 mg·kg^–1,在低、中、高3种加标水平下,平均回收率为91.4%～114.8%,RSD为0.1%～4.8%。结论 该方法操作简便、准确,适用于膏乳、水剂、粉类及精油类化妆品中22种香豆素类化合物的检测。     

Immobilising effect of Ruta graveolens L. on human spermatozoa: coumarin compounds are involved

This study was designed to find out Ruta graveolens L. functional components, which have immobilisation effect on human spermatozoa for contraceptive use. A five‐step fractionation method was used to derive different components from rue aqueous extract by using hexane, chloroform, ethanol, acetone and ultrapure water. Gas chromatography–mass spectrophotometery (GC–MS) of all fractions and the aqueous extract were performed to determine the chemical components. The immobilisation assay and membrane integrity test were also performed with four different coumarins, which were found in GC–MS in a concentration of 10 μm . Hexane, chloroform, acetone and ethanol fractions could significantly decrease motility of sperms within the first and the second hours. Hexane fraction had also significant immediate effect. The aqueous fraction had no effect on sperm motility. Meanwhile, GC–MS revealed that aqueous extract and effective fractions had similar coumarin compounds. We performed the immobilisation assay on four different coumarins, which were found in GC–MS in a concentration of 10 μm . Reduction of sperm motility was only significant for xanthotoxin. In the sperm viability and membrane integrity tests, hexane and ethanolic fractions could impair sperm vitality significantly, in contrast to coumarins. These results indicated that a part of immobilising effect of rue could be due to its coumarins. The possible mechanism could be blocking of spermatozoa potassium channels.     

黄脉九节的化学成分研究

综合运用硅胶柱色谱、Sephadex LH-20凝胶柱色谱、ODS反相柱色谱及制备型高效液相等色谱分离技术,对茜草科九节属植物黄脉九节Psychotria straminea枝叶的化学成分进行系统的分离和纯化。根据化合物的理化性质和波谱数据,并通过与文献对照,鉴定了从黄脉九节枝叶95%乙醇提取物的石油醚萃取部位中分离得到的16个化合物,包括8个黄酮类化合物、3个香豆素类化合物和5个三萜类化合物,分别鉴定为杨芽黄素(1)、芹菜素(2)、山柰酚(3)、木犀草素(4)、香叶木素(5)、槲皮素(6)、山柰酚-4''-O-甲醚(7)、鼠李素(8)、7-羟基香豆素(9)、7-甲氧基香豆素(10)、东莨菪内酯(11)、羽扇豆醇(12)、30-醛基羽扇豆醇(13)、羽扇豆醇乙酸酯(14)、α-香树脂醇(15)和熊果酸(16)。该研究首次对黄脉九节的化学成分进行了系统研究,除化合物6和9为首次从黄脉九节中分离得到以外,其他化合物均为首次从九节属植物中分离得到。     

蛇床子中的细胞毒活性香豆素

研究植物蛇床Cnidium monnieri干燥成熟果实中的香豆素类成分及其细胞毒活性,为进一步开发利用蛇床子提供依据。采用大孔树脂、硅胶和Sephadex LH-20、C₁₈柱色谱等方法分离纯化,并运用波谱方法对所分离的化合物进行结构鉴定。采用MTT法对所分离得到的化合物进行L1210癌细胞毒活性实验。从蛇床子中分离鉴定了11个香豆素类化合物,分别为蛇床子素(1)、佛手柑内酯(2)、花椒毒酚(3)、花椒毒素(4)、欧前胡素(5)、异虎耳草素(6)、欧前胡素酚(7)、补骨脂素(8)、5,7-二甲氧基香豆素(9)、水合羟基前胡内酯(10)、swietenocoumarin F(11)。化合物 7,9~11 为首次从蛇床属植物中分离得到。在样品溶液浓度为1×10^-5 mol·L^-1的条件下,化合物 1,5,10, 11 对小鼠白血病L1210细胞体外生长的抑制率分别是70.13%,63.10%,55.77%,75.08%,表明上述化合物对L1210细胞具有较明显的体外细胞毒活性。     

中药有效成分治疗高尿酸血症基础研究进展

对高尿酸血症(HUA)具有治疗作用的中药主要有效成分有黄酮类如槲皮素、越桔果渣黄酮、葛根素和红旱莲总黄酮等,皂苷类如穿山龙总皂苷和萆薢总皂苷等,香豆素类如秦皮总香豆素和岩白菜素等。这些有效成分可以通过多个靶点和作用机制防治HUA,已阐明的主要机制包括:1直接促进尿酸排泄,抑制尿酸生成;2直接抑制血清和肝黄嘌呤氧化酶和腺苷脱氨酶活性;3下调肾尿蛋白转运体1和葡萄糖转运子9及其基因表达预防尿酸过度生成,上调肾有机阴离子转运体1蛋白及其基因表达促进尿酸排泄;4调节雌二醇和三磷酸甘油醛脱氢酶水平;5改善或减少HUA的脂质过氧化。     

Mining large heterogeneous data sets in drug discovery

ABSTRACT

Introduction: Selective monoamine oxidase-B (MAO-B) inhibitors are currently used as coadjuvants for the treatment of early motor symptoms in Parkinson’s disease. They can, based on their chemical structure and mechanism of inhibition, be categorized into reversible and irreversible agents.

Areas covered: This review provides a comprehensive update on the development state of selective MAO-B inhibitors describing the results, structures, structure–activity relationships (SARs) and Medicinal chemistry strategies as well as the related shortcomings over the past five years.

Expert opinion: Researchers have explored and implemented new and old chemical scaffolds achieving high inhibitory potencies and isoform selectivity. Most of them were characterized and proposed as multitarget agents able to act at different levels (including AChE inhibition, H3R or A_2AR antagonism, antioxidant and chelating properties, Aβ_1-42 aggregation reduction) in the network of aetiologies of neurodegenerative disorders. These results can also be used to avoid ‘cheese-reaction’ effects and the occurrence of serotonergic syndrome in patients.     

International Normalized Ratio (INR), coagulation factor activities and calibrated automated thrombin generation – influence of 24 h storage at ambient temperature

International Normalized Ratio (INR) measurements are used to monitor oral anticoagulation therapy with coumarins. Single coagulation factor activities and calibrated automated thrombin (CAT) generation are considered as more advanced methods for evaluating overall haemostatic capacity. The aims were to assess the variability of INR, coagulation factor activities, and CAT, during 24 h of storage of blood samples at ambient temperature. A total of 24 patients on stable coumarin treatment were followed prospectively for 6 weeks. INR was analyzed at 0, 6 and 24 h after blood sampling and 1-stage clotting activity of coagulation factors II, VII, IX, and X as well as CAT generation was recorded after 0 and 24 h respectively. Statistical analyses included Bland–Altman plot, 95% limits of agreement, and a variability test using a mixed effect model. The level of INR remained statistically unchanged from 0 to 6 and 24 h of storage. Coagulation factor activities and CAT revealed no significant difference induced by 24 h of storage, although the limits of agreement were wide. Patients’ individual INR, coagulation factor activities, and CAT generation were not significantly influenced by 24 h storage of blood samples, but for the CAT generation analyses a trend toward time dependency was detected.