PPA受体天然激动剂的研究进展

从天然产物中筛选低毒高效的PPARs(peroxisome proliferators activated receptors)激动剂已成为开发治疗代谢综合症药物的研究热点。现针对近年来关于PPARs天然激动剂的研究报道进行综述,包括药用和食用植物、复方中药,以及生理活性物质中含有的PPARs三个亚型α、β、γ的激动剂,或是PPARs的双重和泛天然激动剂,这些天然产物均能通过激动PPARs发挥治疗预防疾病和调节生理功能的作用。     

Impact of natural products in modern drug development

Usage of natural substances as therapeutic agents in modern medicine has sharply declined from the predominant position held in the early decades of last century, but search for bioactive molecules from nature (plants, animals, microflora) continues to play an important role in fashioning new medicinal agents. With the advent of modern techniques, instrumentation and automation in isolation and structural characterisation, we have on hand an enormous repository of natural compounds. In parallel to this, biology has also made tremendous progress in expanding its frontiers of knowledge. An interplay of these two disciplines constitutes the modern thrust in research in the realm of compounds elaborated by nature. The purpose of this article is to underline how natural products research continues to make significant contributions in the domain of discovery and development of new medicinal products. It is proposed to present the material under several heads, each of which has made natural products research relevant in the search for new and better medication.     

保肝降酶的天然药物研究进展

天然药物治疗肝损伤的功效及其低毒性已得到广泛的认可。由于大多肝损伤均有氧化应激的参与,天然药物的保肝作用通常与其抗氧化特性或激发体内抗氧化防御系统的能力有关。然而,越来越多的证据表明,除了抗氧化,天然药物还具有许多其他保肝机制。文章综述了近年来保肝降酶的天然药物的研究进展,将国内外已报道的天然药物分黄酮类、生物碱类、皂苷类、多糖类、木脂素类、萜类及其他类并分别列举其治疗机制及效果,为天然药物保肝降酶相关性的研究提供文献依据和研究思路,并对未来保肝降酶的新药研发方向进行展望。     

保肝降酶的天然药物研究进展

天然药物治疗肝损伤的功效及其低毒性已得到广泛的认可。由于大多肝损伤均有氧化应激的参与,天然药物的保肝作用通常与其抗氧化特性或激发体内抗氧化防御系统的能力有关。然而,越来越多的证据表明,除了抗氧化,天然药物还具有许多其他保肝机制。文章综述了近年来保肝降酶的天然药物的研究进展,将国内外已报道的天然药物分黄酮类、生物碱类、皂苷类、多糖类、木脂素类、萜类及其他类并分别列举其治疗机制及效果,为天然药物保肝降酶相关性的研究提供文献依据和研究思路,并对未来保肝降酶的新药研发方向进行展望。     

From traditional Chinese medicine to rational cancer therapy

Many natural products and derivatives thereof belong to the standard repertoire of cancer chemotherapy. Examples are Vinca alkaloids, taxanes and camptothecins. In recent years, the potential of natural products from plants, notably from medicinal plants used in traditional Chinese medicine (TCM), has been recognized by the scientific community in the Western world. To provide an example of the most recent developments in this field, we have selected several compounds, namely artesunate, homoharringtonine, arsenic trioxide and cantharidin, that are found in natural TCM products and that have the potential for use in cancer therapy. Controlled clinical studies have shown that homoharringtonine and arsenic trioxide can exert profound activity against leukaemia. Increased knowledge of the molecular mechanisms of TCM-derived drugs and recent developments in their applications demonstrate that the combination of TCM with modern cutting-edge technologies provides an attractive strategy for the development of novel and improved cancer therapeutics.     

Exploring anti-TB leads from natural products library originated from marine microbes and medicinal plants

Multidrug-resistant tuberculosis (MDR-TB) and TB–HIV co-infection have become a great threat to global health. However, the last truly novel drug that was approved for the treatment of TB was discovered 40?years ago. The search for new effective drugs against TB has never been more intensive. Natural products derived from microbes and medicinal plants have been an important source of TB therapeutics. Recent advances have been made to accelerate the discovery rate of novel TB drugs including diversifying strategies for environmental strains, high-throughput screening (HTS) assays, and chemical diversity. This review will discuss the challenges of finding novel natural products with anti-TB activity from marine microbes and plant medicines, including biodiversity- and taxonomy-guided microbial natural products library construction, target- and cell-based HTS, and bioassay-directed isolation of anti-TB substances from traditional medicines.     

Sesquiterpene coumarins

Plants have a long history as therapeutic tools in the treatment of human diseases and have been used as a source of medicines for ages. In search of new biologically active natural products, many plants and herbs used in traditional medicine are screened for natural products with pharmacological activity. In this paper, we present a group of natural products, the sesquiterpene coumarins isolated from plants, and describe their wide range of biological activity. Sesquiterpene coumarins are found in some plants of the families Apiaceae (Umbelliferae), Asteraceae (Compositae) and Rutaceae. The coumarin moiety is often umbelliferone (7-hydroxycoumarin) but scopoletin (7-hydroxy-6-methoxycoumarin) and isofraxidin (7-hydroxy-6,8-dimethoxycoumarin) are also found. These coumarins are linked to a C₁₅ terpene moiety through an ether linkage. Another group of sesquiterpene coumarins is the prenylated 4-hydroxycoumarins where the link between the coumarin and the C₁₅ terpene moiety is a C–C-bond at carbon 3 of the coumarin moiety. Finally, the prenyl-furocoumarin-type sesquiterpenoids are a separate group of sesquiterpene coumarins based on the suggested biosynthetic pathway. Our relatively limited knowledge on the biosynthesis of sesquiterpene coumarins is reviewed.     

Making small molecules in plants: A chassis for synthetic biology-based production of plant natural products

Plant natural products have been extensively exploited in food,medicine,flavor,cosmetic,renewable fuel,and other industrial sectors.Synthetic biology has recently emerged as a promising means for the cost-effective and sustainable production of natural products.Compared with engineering microbes for the production of plant natural products,the potential of plants as chassis for producing these compounds is underestimated,largely due to challenges encountered in engineering plants.Knowledge in pl...     

Natural products and derivatives affecting neurotransmission relevant to Alzheimer's and Parkinson's disease

The two major neurodegenerative diseases Alzheimer's disease (AD) and Parkinson's disease (PD) are characterised by low levels in the brain of the neurotransmitters acetylcholine (ACh) and dopamine (DA), respectively. Clinical treatment of these two conditions is palliative and relies, in most cases, on improving stimulation at the relevant receptors by either increasing levels of the endogenous neurotransmitter or by the use of substances which have a similar agonist response. Natural products continue to provide useful drugs in their own right but also provide templates for the development of other compounds. The major advances in the treatment of AD have been the use of acetylcholinesterase inhibitors such as galantamine, huperzine A, physostigmine and its derivatives to increase the levels of ACh rather than the use of cholinergic compounds, although compounds with nicotinic properties have attracted some interest. In contrast, the treatment of PD has relied on the elevation of DA levels by use of L-DOPA, its precursor, and by the administration of dopaminergic agonists, especially the ergot alkaloid derivatives. The use of inhibitors of enzymes that cause breakdown of DA is an avenue which is being explored. As well as the major natural products of clinical interest, the paper discusses the chemistry, activity and usage of the constituents of plants used in traditional medicine for the treatment of diseases presenting symptoms similar to those characteristic for Alzheimer's or Parkinson's disease.     

A call for using natural compounds in the development of new antimalarial treatments - an introduction

Natural compounds, mostly from plants, have been the mainstay of traditional medicine for thousands of years. They have also been the source of lead compounds for modern medicine, but the extent of mining of natural compounds for such leads decreased during the second half of the 20th century. The advantage of natural compounds for the development of drugs derives from their innate affinity for biological receptors. Natural compounds have provided the best anti-malarials known to date. Recent surveys have identified many extracts of various organisms (mostly plants) as having antiplasmodial activity. Huge libraries of fractionated natural compounds have been screened with impressive hit rates. Importantly, many cases are known where the crude biological extract is more efficient pharmacologically than the most active purified compound from this extract. This could be due to synergism with other compounds present in the extract, that as such have no pharmacological activity. Indeed, such compounds are best screened by cell-based assay where all potential targets in the cell are probed and possible synergies identified. Traditional medicine uses crude extracts. These have often been shown to provide many concoctions that deal better with the overall disease condition than with the causative agent itself. Traditional medicines are used by ~80 % of Africans as a first response to ailment. Many of the traditional medicines have demonstrable anti-plasmodial activities. It is suggested that rigorous evaluation of traditional medicines involving controlled clinical trials in parallel with agronomical development for more reproducible levels of active compounds could improve the availability of drugs at an acceptable cost and a source of income in malaria endemic countries.     

Potential dermatological application on Asian plants

Skin diseases are among some of the most common types of health problems faced in Malaysia, as reported by the World Health Organization (WHO). Correspondingly, research into the use of medicinal plants for skin disease treatment has become important. Through the ages, medicinal plants have been used widely to treat a variety of skin diseases. The demand for plant-based medicines is growing, as they are generally considered to be safer and less harmful than conventional allopathic drugs. This article reviews the potential of Asian plants to be epidermal protecting agents. There are eleven remarkable Asian plants that are known for their skin barrier protecting agent properties. Important studies have shown that natural products offer a rich potential source of epidermal protecting agents. Nevertheless, further surveys and clinical evidence are needed to establish the potential of identified species in contributing to the treatment of skin disease, especially atopic eczema.     

Bio-mining the microbial treasures of the ocean: new natural products

The biological resources of the oceans have been exploited since ancient human history, mainly by catching fish and harvesting algae. Research on natural products with special emphasis on marine animals and also algae during the last decades of the 20th century has revealed the importance of marine organisms as producers of substances useful for the treatment of human diseases. Though a large number of bioactive substances have been identified, some many years ago, only recently the first drugs from the oceans were approved. Quite astonishingly, the immense diversity of microbes in the marine environments and their almost untouched capacity to produce natural products and therefore the importance of microbes for marine biotechnology was realized on a broad basis by the scientific communities only recently. This has strengthened worldwide research activities dealing with the exploration of marine microorganisms for biotechnological applications, which comprise the production of bioactive compounds for pharmaceutical use, as well as the development of other valuable products, such as enzymes, nutraceuticals and cosmetics. While the focus in these fields was mainly on marine bacteria, also marine fungi now receive growing attention. Although culture-dependent studies continue to provide interesting new chemical structures with biological activities at a high rate and represent highly promising approaches for the search of new drugs, exploration and use of genomic and metagenomic resources are considered to further increase this potential. Many efforts are made for the sustainable exploration of marine microbial resources. Large culture collections specifically of marine bacteria and marine fungi are available. Compound libraries of marine natural products, even of highly purified substances, were established. The expectations into the commercial exploitation of marine microbial resources has given rise to numerous institutions worldwide, basic research facilities as well as companies. In Europe, recent activities have initiated a dynamic development in marine biotechnology, though concentrated efforts on marine natural product research are rare. One of these activities is represented by the Kieler Wirkstoff-Zentrum KiWiZ, which was founded in 2005 in Kiel (Germany).     

Importance of flavonoids in insect--plant interactions: feeding and oviposition

Jeffrey Harborne and colleagues have been responsible for collating the majority of data on the role of flavonoids in insect plant interactions. This article examines some of this information and assesses our knowledge about the role flavonoids play in insect feeding and oviposition behaviour. It is clear that insects can discriminate among flavonoids and that these compounds can modulate the feeding and oviposition behaviour of insects, but further work is required to understand the neural mechanisms associated with these behavioural responses. Despite the wealth of data about the diversity of flavonoids in plants, very few of these compounds have been tested against insects and their role in the evolution of host range in insect--plant interactions has yet to be determined.     

From tradition to innovation: the search for novel therapeutic molecules to treat diabetes

There are over a hundred chemical substances that have been derived from plants for use as drugs and medicines; many more await and medicinal plants are the target of all the attention. The structural diversity of natural products still surpasses that from synthetic compounds and is far beyond any imagination of experts in the field. For many pharmaceutical companies, it is a good argument to investigate natural compounds. Many plants with antidiabetic virtues are known in traditional medicine over the world. The CPID (Centre de Pharmacologie et Innovation dans le Diabète) proposes a technology program to purify new natural antidiabetic substances. A large antidiabetic plant library is constructed for a high-throughput pharmacological screening with cell cultures.     

Bioactive molecules from protists: Perspectives in biotechnology

For hundreds of years, mankind has benefited from the natural metabolic processes of microorganisms to obtain basic products such as fermented foods and alcoholic beverages. More recently, microorganisms have been exploited for the production of antibiotics, vitamins and enzymes to be used in medicine and chemical industries. Additionally, several modern drugs, including those for cancer therapy, are natural products or their derivatives. Protists are a still underexplored source of natural products potentially of interest for biotechnological and biomedical applications. This paper focuses on some examples of bioactive molecules from protists and associated bacteria and their possible use in biotechnology.     

Natural products for cancer chemotherapy

For over 40 years, natural products have served us well in combating cancer. The main sources of these successful compounds are microbes and plants from the terrestrial and marine environments. The microbes serve as a major source of natural products with anti‐tumour activity. A number of these products were first discovered as antibiotics. Another major contribution comes from plant alkaloids, taxoids and podophyllotoxins. A vast array of biological metabolites can be obtained from the marine world, which can be used for effective cancer treatment. The search for novel drugs is still a priority goal for cancer therapy, due to the rapid development of resistance to chemotherapeutic drugs. In addition, the high toxicity usually associated with some cancer chemotherapy drugs and their undesirable side‐effects increase the demand for novel anti‐tumour drugs active against untreatable tumours, with fewer side‐effects and/or with greater therapeutic efficiency. This review points out those technologies needed to produce the anti‐tumour compounds of the future.     

Phytochemistry and pharmacognosy

During the past 50 years there have been tremendous advances in chemical and biological techniques of analysis that have transformed research in pharmacognosy. The PSE has regularly held symposia of relevance to pharmacognosy and some of these are briefly reviewed in the area of natural products from higher plants. These symposia have charted the developments that link pharmacognosy with phytochemistry and illustrate the application of increasingly more sophisticated analytical techniques to the discovery of biologically active compounds. Plants have yielded clinical drugs, either as natural product molecules, or as synthetic modifications, particularly for chemotherapeutic treatment of cancer and malaria. Aspects of biotechnology, traditional medicines and herbal medicinal products are briefly discussed.     

Insect natural products and processes: new treatments for human disease

In this overview, some of the more significant recent developments in bioengineering natural products from insects with use or potential use in modern medicine are described, as well as in utilisation of insects as models for studying essential mammalian processes such as immune responses to pathogens. To date, insects have been relatively neglected as sources of modern drugs although they have provided valuable natural products, including honey and silk, for at least 4-7000 years, and have featured in folklore medicine for thousands of years. Particular examples of Insect Folk Medicines will briefly be described which have subsequently led through the application of molecular and bioengineering techniques to the development of bioactive compounds with great potential as pharmaceuticals in modern medicine. Insect products reviewed have been derived from honey, venom, silk, cantharidin, whole insect extracts, maggots, and blood-sucking arthropods. Drug activities detected include powerful antimicrobials against antibiotic-resistant bacteria and HIV, as well as anti-cancer, anti-angiogenesis and anti-coagulant factors and wound healing agents. Finally, the many problems in developing these insect products as human therapeutic drugs are considered and the possible solutions emerging to these problems are described.     

天然活性成分作用靶点识别及确证方法的研究进展

药物靶标的发现和验证是新药研发的关键环节,对新药创制具有源头创新意义。天然产物是新药创制的重要来源,识别其作用靶点不仅为临床预防治疗提供可能新策略,也为进一步阐释中草药及其复方的作用特点及分子机制提供参考依据。随着生命科学和信息学的发展,药物靶点的识别及确证方法不断涌现,生物信息学、网络药理学、蛋白质组学、亲和色谱、药物亲和稳定性、芯片技术、基因敲除技术、RNA干扰等技术的广泛应用,越来越多的天然活性成分的靶点得以识别和验证。因此,本文对近五年来天然活性成分作用靶点识别及确证方法做一简要综述,以供参考。     

植物天然产物微生物重组合成研究进展

植物天然产物是小分子药物、营养品、化妆品、香精香料等的主要来源之一,在国民经济中发挥重要的作用。目前植物天然产物主要依赖于植物提取,这种生产方式占用耕地、生长周期长,而且植物活性成分往往含量低、生产成本高。通过解析植物天然产物生物合成途径,在微生物细胞中重构,创建细胞工厂,实现利用可再生原料发酵合成,为植物天然产物的供给提供了新的路线。本文重点介绍了中国科学院天津工业生物技术研究所在萜类、黄酮类、苯丙素类等重要类型植物天然产物微生物重组合成方面的研究进展,简要探讨了当前研究面临的挑战及未来前景。