Inhibitory activity of a series of coumarins on leukocyte eicosanoid generation

Sixteen plant-derived or synthetic coumarins with different patterns of substitution were tested for their capacity to modify A23187-induced synthesis of leukotriene B₄ and thromboxane B₂ via the 5-lipoxygenase and cyclooxygenase pathways of arachidonate metabolism in rat peritoneal exudate leukocytes. Five of the 16 coumarins inhibited LTB₄ production: all containortho-dihydroxy substitutions (approximate IC₅₀ values 8–100 M). The mechanism is likely to depend upon a combination of the coumarins' iron-chelating and iron ion-reducing abilities, properties which also confer beneficial activities of these compounds as scavengers of reactive oxygen species (Payá et al., Biochem. Pharmacol.44, 205–214 (1992)). Inhibition of the cyclooxygenase pathway was only demonstrated by one compound, 5,7-dihydroxy-4-methylcoumarin, which did not inhibit 5-lipoxygenase, indicating that the cyclooxygenase inhibitory mechanism is different. Similar effects of the active coumarins were obtained using arachidonic acid as substrate for rat leukocyte eicosanoid generation, confirming that they act at the 5-lipoxygenase/cyclooxygenase level. The same profile of activity was also shown when the coumarins were tested against 5-lipoxygenase in human polymorphonuclear neutrophils. Taken together, these antioxidant and anti-eicosanoid properties of coumarins could be exploited for the design of potentially valuable non-toxic anti-inflammatory agents for treating diseases in which eicosanoid generation and the production of reactive oxygen species are involved.     

3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-one (CHP) inhibits human ovarian cell proliferation by inducing apoptosis

Coumarins induce apoptosis by activating mitochondrial pathway and caspase-3-dependent apoptotic pathway. In the present study, we first time investigated the effect of 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-one (CHP) on induction of apoptosis in human ovarian carcinoma cells. The data from MTT assay revealed a significant inhibitory effect on cell viability at 30 (87%) and 50 μM (74%) concentration of CHP in OVCAR-3 and OVCAR-420 cells, respectively after 72 h. Apoptosis analysis using annexin V/PI double staining followed by flow cytometry showed 59 and 52% binding to annexin V-FITC in OVCAR-3 and OVCAR-420 cells respectively. propidium iodide (PI) staining and flow cytometry examination indicated a significant increase in percentage of cells in G2/M phase after treatment with CHP compared to DMSO control group. Reactive oxygen species (ROS) assay kit showed increase in levels of ROS. We used rhodamine-123 (Rh-123) staining and flow cytometry assay to determine changes in mitochondrial membrane potential (ΛΨm). The results revealed that CHP significantly decreased MMP to 85.65 ± 1.2443% & 49.78 ± 1.6554% at 10 and 30 μM respectively in OVCAR-3 compared to 95.97 ± 2.1243% in control group. Western blot analysis clearly indicated a significant increase in the expression of Caspase-3, Bax, and release of Cytochrome c and decrease in Bcl-2, CDK1 and Cyclin B1 expression on treatment with CHP. Therefore, CHP may become a potential candidate for the treatment of human ovarian cancers.     

水曲柳皮总香豆素提取工艺研究

目的筛选水曲柳总香豆素的最佳提取工艺。方法采用正交实验设计L9（3^4）考察浸渍时间，乙醇浓度，水浴温度，提取时间4个因素对提取工艺的影响。结果水曲柳中总香豆素含量的最佳工艺为水曲柳粗粉加25倍量95％乙醇，室温超声提取45min。结论优选的超声提取条件工艺简单，成本低，节能省时，可增加水曲柳的利用率。     

香豆素类化合物的药理研究进展

通过查阅相关文献,对香豆素类化合物药理作用的研究现状进行综述。香豆素类化合物具有镇痛抗炎、抗艾滋病、抗肿瘤、抗氧化、降压、抗心律失常等多方面的生物活性,为香豆素类化合物的深入研究提供参考。     

黄花败酱的化学成分研究

目的：对黄花败酱的化学成分进行研究。方法：采用乙醇提取，溶剂萃取，硅胶柱层析，重结晶等从败酱科植物黄花败酱的全草中提取分离活性成分，通过波谱解析及化学方法进行结构鉴定。结果：自黄花败酱醇提物中分得8个化合物。结论：除文献报道过的齐墩果酸（oleanolic acid)，东茛菪素（scopoletin)，β－谷甾醇（β－sitosterol)和β－胡萝卜甙（daucostarine)外，还首次从黄花败酱中分到2α－羟基齐墩果酸（2α－hydroxyoleanolic acid),2α-羟基乌苏酸（2α－hydroxyursolic acid)，齐墩果酸－3－O－β－D－吡喃木糖苷（oleanoliic adic-3-O-β-D-xylopyranoside)和3，4－二羟基苯甲酸（3，4－dihydroxybenzoic acid)。     

蛇床子总香豆素的抗炎作用

蛇床子总香豆素（ＴＣＣＭ）对角叉菜胶和鸡蛋清引起的大鼠足跖肿均有明显的抑制作用。ＴＣＣＭ还能减轻二甲苯引起的耳壳肿胀，明显抑制大鼠滤纸片肉芽肿。     

九里香化学成分的研究

自广东产芸香科(Rutaceae)植物九里香(Murraya paniculata(L.)Jack.)叶中分离得到六个香豆精,其中三个化合物为新的香豆精,根据光谱(UV,IR,NMR和MS)分析和化学方法确定九里香甲素(isomexoticin)九里香乙素(murpanidin)和九里香丙素(murpanicin)分别为(一)5,7-二甲氧基-8-(2′,3′-二羟基-3′-甲基丁基)香豆精(Ⅰ),(+)7-甲氧基-8-(1′,2′-二羟基-3′-甲基-3′-丁烯基香豆精(Ⅲ)和7-甲氧基-8-(1′-乙氧基-2′-羟基-3′-甲基-3′-丁烯基)香豆精(Ⅳ)。同时也得到三个已知香豆精murragatin(Ⅱ),murralongin(Ⅴ)和5,7-二甲氧基-8-(3′-甲基-2′-酮基丁基)香豆精(Ⅵ),最后一个是首次自本植物中得到的。     

Anti-oxidative and photo-protective effects of coumarins isolated fromFraxinus chinensis

Free radicals and reactive oxygen species (ROS), which are generated by UV irradiation, may cause serious injury to skin cell membranes, DNA and functional proteins. In addition, these agents stimulate the expressions of matrix metalloproteinases (MMPs), which can degrade most components of the extracellular matrix (ECM), including collagen. In order to develop new anti-photoaging agents, five major components from the extract of Fraxinus chinensis extract (FCE) were identified. Two of the major components of FCE were found to be esculin (11.2%) and esculetin (1.9%). FCE (IC50: 50.0 microg/mL 1, 1-diphenyl-2-picrylhydrazyl (DPPH); 19.8 microg/mL, superoxide anion radical) and esculetin (IC50: 2.1 microg/mL DPPH; 0.6 microg/mL, superoxide anion radical) showed strong antioxidative activities. Of the compounds tested, esculetin showed the strongest scavenging activity against DPPH radicals, followed by superoxide anions from the xanthine/xanthine oxidase system. The intracellular ROS scavenging activity showed that oxidation of 5-(6-)-chloromethyl-2', 7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA) was effectively inhibited by esculetin, with potent free radical scavenging activity was also shown in UVB-irradiated human dermal fibroblasts (HDFs). Moreover, treatment of UVA-irradiated HDFs with esculetin resulted in dose-dependent decreases in the expression levels of MMP-1 mRNA and protein. From these results, FCE and one of its components, esculetin, were predicted to be potentially useful as ingredients in cosmetics for protecting against photoaging.     

Inhibitors of NQO1: identification of compounds more potent than dicoumarol without associated off-target effects

The enzyme NAD(P)H quinone oxidoreductase (NQO1) can function both as a detoxifying enzyme as well as chaperone protein. The latter property has been extensively characterized by the use of dicoumarol which inhibits the chaperone properties of NQO1 in cells. However, the use of this compound is compromised by its multiple “off-target” effects. Coumarin-based compounds that are more potent than dicoumarol as inhibitors of NQO1 in cells have been identified (Nolan et al., Biochem Pharmacol 2010;80:977–81). The purpose of the work reported here is to evaluate the off-target effects of these compounds when compared to dicoumarol. A range of these substituted coumarins are identified that are significantly less toxic than dicoumarol in a panel of nine cell lines. Further a number of the compounds generate much less intracellular superoxide, and many of them also show a reduced ability to induce apoptosis when compared to dicoumarol. None of these effects correlate with the ability of the compounds to inhibit the enzymatic activity of NQO1 in cells. In conclusion, potent inhibitors of NQO1 have been identified that will be more pharmacologically useful than dicoumarol for probing the function of NQO1 in cells and tissues.     

Chemical constituents from the aerial parts of Tirpitzia ovoidea

In the present study, we isolated 18 known compounds from Tirpitzia ovoidea (Linaceae), including seven terpenoids (1-7), three simple phenylproponoids (8-10), three coumarins (11-13) and five other compounds (14-18). The structures of these compounds were identified by spectroscopic methods and compared with those reported in the literature. Compounds 1-16 were isolated from this plant as well as the Linaceae family for the first time.