Ethnopharmacology and the development of natural PAF antagonists as therapeutic agents

Ginkgolides are unique twenty-carbon terpenes, occurring naturally only in the roots and leaves of Ginkgo biloba. The molecules incorporate a tert-butyl group and six 5-membered rings, and are specific and potent antagonists of platelet-activating factor (PAF), a potent inflammatory autacoid. Studies in animal models with the most potent ginkgolide, BN 52021, and other specific PAF antagonists have demonstrated that PAF plays an important role in pathologies such as asthma, shock, ischemia, anaphylaxis, graft rejection, renal disease, CNS disorders and numerous inflammatory conditions. Ginkgolides are now being developed as therapeutic agents and very promising results have been obtained in clinical trials on shock, organ preservation and thermal injury. In addition to ginkgolides, several other types of natural PAF antagonists have been identified from various medicinal plants. These compounds have not only helped to explain the pharmacological basis of several traditional medicines, but have also provided man with a valuable new class of therapeutic agents.     

Antimutagenic agents from natural products.

Certain secondary metabolites found in terrestrial and marine plants and organisms have evinced the capability for inhibiting the mutagenicity toward Salmonella typhimurium of a number of mutagens. These include 2-aminoanthracene (2AN), ethylmethanesulfonate (EMS), and benzo-[a]pyrene(B[alpha]P). The sensitivity of the antimutagenicity assay is such that crude extracts can be evaluated and purification of extracts readily followed. Major classes of antimutagenic compounds that have been isolated include flavonoids, coumarins, and cymopols.     

Antileukemic activity of selected natural products in Taiwan

The aim of the present study was to evaluate the antileukemic activity of six chemical classes of pure compounds present in commonly used medicinal plants in Taiwan--such as the genus Plantago. Studies were conducted on a series of human leukemia and lymphoma cell lines. Results showed that water soluble compounds (aucubin, caffeic acid, chlorogenic acid, ferulic acid, p-coumaric acid and vanillic acid) exhibited a weak antileukemic activity (IC50: 26-56 microg/ml, SI: 2-11). On the other hand, water insoluble compounds such as triterpenoids (oleanolic acid and ursolic acid), monoterpene (linalool) and flavonoid (luteolin) possessed strong activity against human leukemia and lymphoma cell lines. Among them, linalool showed the strongest activity against histiocytic lymphoma cells U937 (IC50: 3.51 microg/ml, SI: 592.6) and Burkitt lymphoma cells P3HR1 (IC50: 4.21 microg/ml, SI: 494.1). Ursolic acid was effective against P3HR1 cells (IC50: 2.5 microg/ml, SI: 262.6) and chronic myelogenous leukemia cells K562 (IC50: 17.79 microg/ml, SI: 36.91), whereas oleanolic acid inhibited the growth of P3HR1 cells (IC50: 26.74 microg/ml, SI: 11.37). Luteolin exhibited effective activity against K562 cells (IC50 18.96 microg/ml, SI: 5.14) and P3HR1 cells (IC50: 18.99 microg/ml, SI: 5.13). We conclude that terpenes and flavonoid in commonly used medicinal plants possess strong activity against lymphoma and leukemia cells, especially human lymphoma cells, suggesting the potential use of these compounds for treatment of lymphoma.     

Natural products as a source of potential cancer chemotherapeutic and chemopreventive agents

Recent advances in the chemistry of novel bioactive natural products are reported. This research is directed to the exploration of plants with confirmed activity in bioassays designed to detect potential cancer chemotherapeutic and chemopreventive agents. Structural work and chemical studies are reported for several cytotoxic agents from the plants Annona densicoma, Annona reticulata, Claopodium crispifolium, Polytrichum obioense, and Psorospermum febrifugum. Studies are also reported based on development of a mammalian cell culture benzo[a]pyrene metabolism assay for the detection of potential anticarcinogenic agents from natural products. In this study a number of isoflavonoids and flavonoids with antimutagenic activity have been discovered.     

The interaction of selected natural products with human recombinant glutathione transferases

The interaction of geshoidin, diospyrin and ergothioneine, with heterologously expressed human glutathione transferases (GSTs) was investigated in vitro. Diospyrin and geshoidin inhibited the three GST isoforms tested, with IC50 values in the range 0.1-0.5 microm, whereas ergothioneine had no effect on the GSTs. The predominant mode of inhibition was noncompetitive with respect to both glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB). Diospyrin, however, competitively inhibited A1-1 and M1-1 with respect to GSH and geshoidin displayed mixed inhibition toward A1-1 with respect to GSH. The Ki values for diospyrin with respect to both GSH and CDNB were in the range 0.08-0.6 microM and those for geshoidin were in the range 16-173 microM. These results indicate that diospyrin is a potent inhibitor of heterologously expressed human GSTs A1-1, M1-1 and P1-1. Diospyrin and geshoidin were also found to inactivate P1-1 with diospyrin being a potent inactivator. Given these inhibitory properties, diospyrin may be a potential GST chemomodulator. Ergothioneine inactivated P1-1 only after preincubation and it enhanced ethacrynic acid inactivation of P1-1. Inactivation of P1-1 by ergothioneine may have implications for the antioxidant roles of P1-1 and ergothioneine in vivo.     

Potential of natural products as insect antifeedants

Insect antifeedants are the substances that play a significant role in host plant selection by phytophagous insects. Extensive work has been done on natural antifeedants and a large number of these compounds have been identified belonging to different classes during the past decade. The present article deals with various chemical and biological aspects of insect antifeedants and with their possible role in insect pest management.     

抗癌及抗艾滋病天然药物在美国的研发现状

简要叙述了美国抗癌及抗艾滋病天然药物研究发展现状,特别介绍了活性海洋天然气的最新研究进展,列出了目前已进入临床试验阶段的海洋活性物质的化学结构,介绍了美国国家癌症研究院（NCI）选中并支持进行临床前研究的部分活性海洋天然产物,简要介绍了北卡罗来纳大学药学院天然产物实验室在抗艾滋病活 天然产物研究领域的贡献,亦论及了新技术,新方法在药研究中的应用及局限性,进而阐述了从天然产物研发新药的前景与重要意义。     

Marine natural products as novel antioxidant prototypes

Pure natural products isolated from marine sponges, algae, and cyanobacteria were examined for antioxidant activity using a 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) solution-based chemical assay and a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) cellular-based assay. The DCFH system detects only antioxidants that penetrate cellular membranes. Potent antioxidants were identified and the results from each system compared. The algal metabolites cymopol (1), avrainvilleol (3), and fragilamide (4), and the invertebrate constituent puupehenone (5) showed strong antioxidant activity in both systems. Several compounds were active in the DPPH assay but significantly less active in the DCFH system. The green algal metabolite 7-hydroxycymopol (2) was isolated from Cymopolia barbataand its structure determined. Compound 2 was significantly less active in the DCFH system than cymopol (1). The sponge metabolites (1S)-(+)-curcuphenol (6), aaptamine (7), isoaaptamine (8), and curcudiol (9) and the cyanobacterial pigment scytonemin (10) showed strong antioxidant activity in the DPPH assay, but were relatively inactive in the DCFH system. Thus, cellular uptake dramatically affects the potential significance of antioxidants discovered using only the DPPH assay. The apparent "proantioxidants" hormothamnione A diacetate (11) and Laurencia monomer diacetate (12) require metabolic activation for antioxidant activity. Significant advantages are achieved using both a solution- and cellular-based assay to discover new antioxidants.     

In vitro antimycotic activity of some natural products against Saprolegnia ferax

During the in vitro screening of four essential oils and six substances of vegetable origin against the test fungi Saprolegnia ferax, thyme and savory essential oils, carvacrol and thymol exhibited the best antifungal activity at the lower concentrations. The antimycotic activity of malachite green, formalin and sodium chloride was also tested.     

Phenolic marine natural products as aldose reductase inhibitors

Four different types of marine natural compounds isolated from tunicates were found to inhibit human aldose reductase. They all are characterized by a heterocyclic system, and at least two phenolic groups are present in the structure. Two of the compounds tested showed an inhibitory potency 5/6-fold higher than that of the known AR inhibitor sorbinil. One notable structural feature of these active compounds is the lack of either the carboxylic acid or the spiro-hydantoin commonly present in the principal classes of currently used inhibitors.     

Potential synergism of natural products in the treatment of cancer

Cancer is the second leading cause of death worldwide. There is thus increased interest in alternative treatment modalities that include chemotherapy, hormonal supplements, surgery, radiation therapy, complementary or alterative medicine, used alone or in combination. Therefore patients who are subjected to combination treatments such as hormonal supplements or alternative medicine face considerable risk of drug-drug interactions. The administration of herbal drugs by patients without a physician's prior counseling is increasing globally and there is a possibility of herb-drug interactions too. Herbal drugs or extracts themselves contain a combination of active constituents, which interact within themselves and also between other prescribed pharmaceutical drugs to either enhance (synergize) or decrease (antagonize) the therapeutic effect. This review focuses on a number of reports of herb-drug interactions, their mechanism of action with a special emphasis on dietetic phytochemicals such as quercetin, genistein, curcumin and catechins. All phytochemicals tend to increase the therapeutic effect by blocking one or more targets of the signal transduction pathway, by increasing the bioavailability of the other drug or, by stabilizing the other drug in the system.     

Alkaloids from Pachysandra terminalis inhibit breast cancer invasion and have potential for development as antimetastasis therapeutic agents

The aim of the present study was to identify potentially useful natural compounds for the development of novel therapeutic agents to inhibit metastasis. A phytochemical investigation of Pachysandra terminalis resulted in the isolation of seven new pregnane alkaloids, terminamines A-G (1-7), and seven known alkaloids (8-14). The structures of 1-7 were elucidated by 1D- and 2D-NMR spectroscopic and mass spectrometric methods. Compounds 1-5 and 8-14 inhibited the migration of MB-MDA-231 breast cancer cells induced by the chemokine epithelial growth factor. In addition, compound 1 inhibited phosphorylation of integrin β(1), which plays an important role in MB-MDA-231 cell adhesion and metastasis.     

A review of natural products and plants as potential antidiabetic drugs

The present paper reviews the active, natural principles and crude extracts of plants which have been experimentally studied for hypoglycemic activity in the last ten years. Phytoconstituents with known structures have been classified in appropriate chemical groups and the active crude extracts have been listed alphabetically according to genus. Data are reported on their pharmacological activity, mechanism of action, toxicity and other properties.     

5种生物碱胃癌多药耐药逆转剂的筛选及机制研究

目的研究骆驼蓬碱、去氢骆驼蓬碱、贝母素甲、贝母素乙和氧化苦参碱对肿瘤细胞多药耐药性(MDR)的逆转作用及机制。方法以胃癌亲本细胞系SGC-7901和MDR细胞系SGC-7901/VCR为细胞模型,采用MTT法检测上述5种生物碱的细胞毒活性及对MDR的逆转效果;用流式细胞仪检测MDR逆转效果最好的贝母素乙对肿瘤细胞内阿霉素(ADR)蓄积的影响;Western blotting法检测P-糖蛋白(P-gp)的表达;Hoechst荧光染色和细胞免疫荧光法检测贝母素乙诱导SGC-7901/VCR细胞凋亡情况。结果骆驼蓬碱、去氢骆驼蓬碱、贝母素甲、贝母素乙和氧化苦参碱均能不同程度地抑制SGC-7901和SGC-7901/VCR细胞的增殖,在非毒剂量下贝母素乙能够显著提高SGC-7901/VCR细胞对ADR的敏感性及细胞内ADR的浓度,降低P-gp表达。贝母素乙联合5-氟尿嘧啶(5-FU)给药可诱导SGC-7901/VCR细胞凋亡,凋亡细胞cleaved caspase-3呈高表达。结论贝母素乙具有作为胃癌MDR逆转剂的潜力,其逆转耐药的机制可能与下调P-gp表达和诱导细胞凋亡有关。     

中药单体联用抗真菌药物抗耐药白色念珠菌的研究现状

近年来,针对耐药白色念珠菌感染的不断出现,有关中药单体联用抗真菌药物对耐药白色念珠菌作用的研究日趋增多。该文重点采用FICI评价法比较多种中药单体与抗真菌药物联用的协同作用,并对目前已阐明的协同机制进行归纳总结。     

Countercurrent separation of natural products

An assessment of the technology and method development in countercurrent chromatography (CCC) and centrifugal partition chromatography (CPC), collectively referred to as countercurrent separation (CS), is provided. More than six decades of CS theory and applications are critically reviewed and developed into a practical guide to CS for natural products research. The necessary theoretical foundation is given for better use of CS in the separation of biological molecules of any size, small to large, and from any matrix, simple to complex. The three operational fundamentals of CS--instrumentation, biphasic solvent systems, and theory--are covered in a prismatic fashion. The goal of this review is to provide the necessary background and references for an up-to-date perspective of CS and to point out its potential for the natural products scientist for applications in natural products chemistry, metabolome, and proteome research involving organisms from terrestrial and marine sources.     

以VEGF/VEGFR为靶点的抗肿瘤天然化合物研究进展

肿瘤是威胁人类生命健康的重大疾病之一,目前抗肿瘤药物研究呈现出多元化发展的趋势,其中以肿瘤血管生成为靶点,开发血管新生抑制剂,已经成为抗肿瘤研究中1个重要的领域。血管内皮生长因子(vascular endothelial growth factor,VEGF)是血管内皮细胞生长和分化的首要因子,在血管生成过程中非常关键。通常VEGF指的是VEGF-A,其结合受体包括血管内皮生长因子受体1(vascular endothelial growth factor receptor 1,VEGFR1)和VEGFR2。目前研究认为,VEGF/VEGFR途径是介导肿瘤血管生成的关键通路。针对VEGF及其受体的靶向治疗可使肿瘤内新生血管减少,有助于抑制肿瘤的增殖、侵袭和转移。传统的中医药在肿瘤辅助治疗方面颇具特色,从中药中筛选和开发具有血管抑制活性的抗肿瘤药物潜力巨大。对以VEGF/VEGFR为靶点的抗肿瘤天然化合物作用机制研究进展进行综述,以期为该类化合物的研究开发提供参考。     

Medicinal and edible lignicolous fungi as natural sources of antioxidative and antibacterial agents

The antioxidant activity of organic extracts of eight fungal species, Ganoderma lucidum, Ganoderma applanatum, Meripilus giganteus, Laetiporus sulphureus, Flammulina velutipes, Coriolus versicolor, Pleurotus ostreatus and Panus tigrinus, was evaluated for free radical (DPPH^· and OH^·) scavenging capacity and an effect on lipid peroxidation, and the antibacterial activity was tested by the agar well diffusion method. The highest DPPH^· scavenging activity was found in the methanol extract of G. applanatum (12.5 μg/mL, 82.80%) and the chloroform extract of G. lucidum (510.2 μg/mL, 69.12%). The same extracts also showed the highest LP inhibition (91.83%, 85.09%) at 500 μg/mL, while the methanol extracts of G. applanatum and L. sulphureus showed the highest scavenging effect on OH^· radicals (68.47%, 57.06%, respectively) at 400 μg/mL. A strong antibacterial activity against Gram‐positive bacteria was also manifested. The antioxidative potencies correlated generally with the total phenol content (0.19–9.98 mg/g). The HPLC determination showed that the majority of analysed species contained gallic and protocatechic acids. Consequently, these fungi are shown to be potential sources of antioxidative and antibacterial agents. Copyright © 2010 John Wiley & Sons, Ltd.