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.     

Antimutagenicity of extracts from crude drugs in Chinese medicines

The antimutagenicity of extracts from crude drugs was studied by the Ames bioassay system. The crude drugs chosen were medical plants used very frequently as Chinese medicines. Each crude drug was extracted with hot water similar to the method of Chinese medical treatment. Antimutagenicity of the extract was found with 4 kinds of crude drugs, Paeoniae radix, Bupleuri radix, Hoelen and Glycyrrhizae radix. Each extract of the crude drug showed a different type of antimutagenic action from the others.     

Metabolic diversity and bioactivity screening of mangrove plants: a review

Mangrove forests are salt tolerant plants confined to the coastal areas and occupy only 5% of the total forest areas of the world. These are the most hostile environment with fluctuating tidal and saline regime and a limited plant species can survive under such condition. Nevertheless, these plants are most valuable resources and provide economic and ecological benefits to the coastal people. Several mangrove species have been used in traditional medicine or have few applications as insecticide and pesticide. Mangroves are biochemically unique, producing wide array of natural products with unique bioactivity. They possess active metabolites with some novel chemical structures which belong to diverse chemical classes such as alkaloids, phenol, steroids, terpenoids, tannins, etc. The present review examines recent investigations on the biological activities of extracts and phytochemicals identified from mangroves and their associates as antimicrobial, antiviral, antioxidant, anticancer and many other properties like antiproliferative, insecticidal, antimalarial, antifeedant, central nervous system depressant and anti-plasmodial etc. The present article also emphasizes and creates an awareness of potential mangroves and their associates as a source of novel medicines, agrochemicals and source of many biologically active compounds.     

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。     

Biological screening of natural products and drug innovation in China

Natural products have been applied to human healthcare for thousands of years. Drug discovery in ancient times was largely by chance and based on clinical practices. As understanding of therapeutic benefits deepens and demands for natural products increase, previously serendipitous discoveries evolve into active searches for new medicines. Many drugs presently prescribed by physicians are either directly isolated from plants or are artificially modified versions of natural products. Scientists are looking for lead compounds with specific structures and pharmacological effects often from natural sources. Experiences and successes of Chinese scientists in this specialized area have resulted in a number of widely used drugs. The tremendous progress made in life sciences has not only revealed many pathological processes of diseases, but also led to the establishment of various molecular and cellular bioassays in conjunction with high-throughput technologies. This is advantageous and permits certain natural compounds that are difficult to isolate and purify, and compounds that are difficult to synthesize, to be assayed. The transition from traditional to empirical and to molecular screening will certainly increase the probability of discovering new leads and drug candidates from natural products.     

Medicinal mushrooms and cancer therapy: translating a traditional practice into Western medicine

Modern medical practice relies heavily on the use of highly purified pharmaceutical compounds whose purity can be easily assessed and whose pharmaceutical activity and toxicity show clear structure-function relationships. In contrast, many herbal medicines contain mixtures of natural compounds that have not undergone detailed chemical analyses and whose mechanism of action is not known. Traditional folk medicine and ethno-pharmacology coupled to bioprospecting have been an important source of many anticancer agents as well as other medicines. With the current decline in the number of new molecular entities from the pharmaceutical industry, novel anticancer agents are being sought from traditional medicine. As the example of medicinal mushrooms demonstrates, however, translating traditional Eastern practices into acceptable evidence-based Western therapies is difficult. Different manufacturing standards, criteria of purity, and under-powered clinical trials make assessment of efficacy and toxicity by Western standards of clinical evidence difficult. Purified bioactive compounds derived from medicinal mushrooms are a potentially important new source of anticancer agents; their assimilation into Western drug discovery programs and clinical trials also provides a framework for the study and use of other traditional medicines.     

A review of medicinal plant of Middle East and North Africa (MENA) region as source in tuberculosis drug discovery

Tuberculosis (TB) is a disease that affects one-third of the world’s population. Although currently available TB drugs have many side effects, such as nausea, headache and gastrointestinal discomfort, no new anti-TB drugs have been produced in the past 30 years. Therefore, the discovery of a new anti-TB agent with minimal or no side effects is urgently needed. Many previous works have reported the effects of medicinal plants against Mycobacterium tuberculosis (MTB). However, none have focused on medicinal plants from the Middle Eastern and North African (MENA) region. This review highlights the effects of medicinal plants from the MENA region on TB. Medicinal plants from the MENA region have been successfully used as traditional medicine and first aid against TB related problems. A total of 184 plants species representing 73 families were studied. Amongst these species, 93 species contained more active compounds with strong anti-MTB activity (crude extracts and/or bioactive compounds with activities of 0–100 µg/ml). The extract of Inula helenium, Khaya senegalensis, Premna odorata and Rosmarinus officinalis presented the strongest anti-MTB activity. In addition, Boswellia papyrifera (Del) Hochst olibanum, Eucalyptus camaldulensis Dehnh leaves (river red gum), Nigella sativa (black cumin) seeds and genus Cymbopogon exhibited anti-TB activity. The most potent bioactive compounds included alantolactone, octyl acetate, 1,8-cineole, thymoquinone, piperitone, α- verbenol, citral b and α-pinene. These compounds affect the permeability of microbial plasma membranes, thus kill the mycobacterium spp. As a conclusion, plant species collected from the MENA region are potential sources of novel drugs against TB.     

A Review of the Chemistry and Biological Activities of Natural Colorants,Dyes, and Pigments: Challenges,and Opportunities for Food,Cosmetics, and Pharmaceutical Application

Natural pigments are important sources for the screening of bioactive lead compounds. This article reviewed the chemistry and therapeutic potentials of over 570 colored molecules from plants, fungi, bacteria, insects, algae, and marine sources. Moreover, related biological activities, advanced extraction, and identification approaches were reviewed. A variety of biological activities, including cytotoxicity against cancer cells, antioxidant, anti-inflammatory, wound healing, anti-microbial, antiviral, and anti-protozoal activities, have been reported for different pigments. Considering their structural backbone, they were classified as naphthoquinones, carotenoids, flavonoids, xanthones, anthocyanins, benzotropolones, alkaloids, terpenoids, isoprenoids, and non-isoprenoids. Alkaloid pigments were mostly isolated from bacteria and marine sources, while flavonoids were mostly found in plants and mushrooms. Colored quinones and xanthones were mostly extracted from plants and fungi, while colored polyketides and terpenoids are often found in marine sources and fungi. Carotenoids are mostly distributed among bacteria, followed by fungi and plants. The pigments isolated from insects have different structures, but among them, carotenoids and quinone/xanthone are the most important. Considering good manufacturing practices, the current permitted natural colorants are: Carotenoids (canthaxanthin, β-carotene, β-apo-8′-carotenal, annatto, astaxanthin) and their sources, lycopene, anthocyanins, betanin, chlorophyllins, spirulina extract, carmine and cochineal extract, henna, riboflavin, pyrogallol, logwood extract, guaiazulene, turmeric, and soy leghemoglobin.     

Bioactive compounds from brown seaweeds: Phloroglucinol,fucoxanthin and fucoidan as promising therapeutic agents against breast cancer

Breast cancer is one of the most common cancers among women and its incidence tends to increase year by year. Chemotherapy is an effective treatment for many types of cancer, however its toxicity in normal cells and acquired tumor resistance to the drug used are considered as the main barriers. New strategies have been proposed to increase the success of anticancer drugs namely it combination with natural dietary compounds, decreasing drug dose administered and reducing its toxicity to normal cells. Seaweeds are rich in bioactive compounds and, in Traditional Chinese Medicine and Japanese folk medicine are used to “treat” tumors. Attending to the attractive biological effects of some seaweed several efforts have been made to isolate the bioactive compounds and explore its action mechanisms. Phloroglucinol, fucoxanthin and fucoidan are bioactive compounds present in brown seaweed showing chemopreventive and chemotherapeutic effects against cancer. Several mechanisms namely antioxidant, cell cycle arrest, induction of cell death and inhibition of metastasis and angiogenesis have been mentioned as responsible for it anticancer activity. Beside the promising biological effects of these compounds, synergistic effects with cytotoxic drugs have been less explored. This review focuses on the potential protective and therapeutic effect – mainly against breast cancer – of the bioactive compounds phloroglucinol, fucoxanthin and fucoidan present in the brown seaweeds. Current knowledge about interaction between each of these compounds and the conventional anticancer drugs and the further research opportunities are discussed.     

Plant extracts as modulators of genotoxic effects

Higher plants used extensively in traditional medicines are increasingly being screened for their role in modulating the activity of environmental genotoxicants. The property of preventing carcinogenesis has been reported in many plant extracts. The observation of a close association between carcinogenesis and mutagenesis has extended the survey to include plant extracts and plant products able to modify the process of mutagenesis, which involves alteration in the genetic material. Natural plant products may, apart from inducing mutations, modify the action of other known mutagens on the living organisms by 1) activating the existing mutagens within the cell, 2) inhibiting the production of mutagens in the cell, 3) synergising the activity of existing mutagens, or 4) activating the promutagens within the cell into mutagens. This review deals with data obtained in the course of research on the modulatory effects of plant extracts on mutagenesis and clastogenesis, two genotoxic phenomena associated with carcinogenesis. In screening for antimutagenic effects, extracts of different plant parts have been used, ranging from leafy vegetables, fruits, and underground storage organs to whole plants. The extracts were prepared mainly in water or organic solvents. Several of these assays have indicated the involvement of certain factors that are intrinsic components of the extracts, ranging from specific compounds like ascorbic acid to vegetable fibres which could act as nonspecific redox agents, free radical scavengers, or ligands for binding metals or toxic principles. The possible ways in which inhibitors of mutagenesis can act include the inhibition of interaction between genes and biochemically reactive mutagens and the inhibition of metabolic activation of indirectly acting mutagens. The effects of toxicants can be observed at the level of chromosomes (clastogenesis) through alterations in chromosome structure (chromosomal aberrations) and number (aneuploidy, polyploidy). A wide range of short-term and long-term screening procedures is available. The most common ones use higher plants or rodents in vivo as test systems for monitoring chromosomal aberrations. Experiments with a number of crude vegetable and fruit extracts have demonstrated their anticlastogenic activities against known cytotoxic agents. The individual components of the extracts—e.g., sulfhydryl and flavonoid compounds, gallic acid, ellagic acid, mucic acid, citric acid, reducing sugars, tannin—are observed to have an additive interaction with the major constituents chlorophyll and ascorbic acid, when modulating the effects of the clastogens. Under certain conditions, plant products may induce mutagenic effects, due to the presence of multiple biological properties. Some inhibitors can stimulate simultaneously both enhancing and detoxifying mechanisms, e.g., inducers of coordinated enzyme activities. Many oxidants can, depending on the redox potential, either accept or donate electrons, rendering them protective or harmful. Plants also play an active role in the accumulation, metabolism, and environmental distribution of xenobiotics. The property of plants to activate promutagens that may enter the food chain is of great significance in view of the large number and types of chemicals to which the plants are exposed. A promutagen is a chemical that is not mutagenic itself but that can be biologically transformed by a plant system into a mutagen. Several methods for studying promutagens from plants were developed both in vivo and in vitro, including plant cell-free systems. Both mutagens and antimutagens can be extracted from the same plant extract depending on the nature of solvents used for extraction. Interaction between inhibitors may lead to synergistic effects. Such combined action may take place through the different inhibitors acting at different levels or being localised at different cellular areas. The greater protection afforded by crude plant extract as compared with an equivalent amount of the purified or synthetic ingredients, as observed withPhyllanthus emblica L. andBeta vulgaris L. var.benghalensis Hort., may be related to this phenomenon. Specific biological action of a drug is due to its specific binding to a functional molecular receptor. In complex plant extracts, the variable observed effects can be attributed to the many chemically reactive species that are formed during the processing and ingestion of the extract, which could act as non-specific redox agents, scavengers of free radicals, and ligands for binding to toxicants. The final effects are obviously the outcome of interactions between the components and their individual and collective interaction with the toxicant. The specificity and efficacy of such responses will be influenced also by the physiological factors influencing the plants and the process of administration of the extract. In utilizing pharmacologically active herbs, both beneficial and potential adverse effects must be taken into account. The actual dose and form of the plant also need to be worked out.     

Secondary transport as an efficient membrane transport mechanism for plant secondary metabolites

Plants produce a large number of secondary metabolites, such as alkaloids, terpenoids, and phenolic compounds. Secondary metabolites have various functions including protection against pathogens and UV light in plants, and have been used as natural medicines for humans utilizing their diverse biological activities. Many of these natural compounds are accumulated in a particular compartment such as vacuoles, and some are even translocated from source cells to sink organs via long distance transport. Both primary and secondary transporters are involved in such compartmentation and translocation, and many transporter genes, especially genes belonging to the multidrug and toxin extrusion type transporter family, which consists of 56 members in Arabidopsis, have been identified as responsible for the membrane transport of secondary metabolites. Better understandings of these transporters as well as the biosynthetic genes of secondary metabolites will be important for metabolic engineering aiming to increase the production of commercially valuable secondary metabolites in plant cells.     

Natural compounds with important medical potential found in Helleborus sp.

Helleborus (family Ranunculaceae) are well-known as ornamental plants, but less known for their therapeutic benefits. Over the past few years, Helleborus sp. has become a subject of interest for phytochemistry, pharmacology and other medical research areas. On the basis of their usefulness in traditional medicine, it was assumed that their biochemical profile could be a source of metabolites with the potential to overcome critical medical issues. There are studies involving natural extracts from these species which demonstrate that Helleborus plants are a valuable source of chemical compounds with great medical potential. Some phytochemicals produced by these species have been separated and identified a few decades ago: hellebrin, deglucohellebrin, 20-hydroxyecdysone and protoanemonin. Lately, many other active compounds have been reported and considered as promising remedies for severe diseases such as cancer, ulcer, diabetes and also for common medical problems such as toothache, eczema, low immunity and arthritis. This paper is an overview of the Helleborus genus focusing on some recentlydiscovered compounds and their potential for finding new drugs and useful biochemicals derived from these species.     

Emerging issues in traditional Chinese medicine

Traditional Chinese medicine (TCM) has many beneficial effects and has been practiced for several thousand years. It is known to treat the cause of a disease rather than to alleviate its symptoms. Based on a belief that TCM is natural, safe, and of lower cost, consumers worldwide are spending more out-of-pocket money on this form of therapy. This increased spending, and reports of adverse reactions, has drawn the attention of many regulatory agencies. Scientists have called for more evidence-based and scientific research on the risks and benefits of TCM. In Canada, the Natural Health Product Regulations came into effect January 2004. TCM herbal product manufacturers will need to provide products of reputable quality to the market. Many will apply modern technology and good science to support their products. The issues facing producers, scientists, and consumers alike are quality control and assessment, standardization of bioactive components, mechanisms of actions, and integration of the evolved modern Chinese medicine into the healthcare system. Solid science, better regulation of the final product, and better education of consumers are necessary to extract the best of TCM to complement existing conventional medicine to deliver the best healthcare.     

Separation methods for antibacterial and antirheumatism agents in plant medicines

Traditional oriental medicines (TOM), with a very long history and many remarkable features, are very popular in Asian countries, especially in China, Japan and Korea. With the development of advanced analytical techniques, the modernization of traditional medicine has become a hot area in recent years and some herbal medicines have been increasingly accepted in western countries. Separation and determination of active components in various herbal medicines are considered to be critical for the modernization process. Antibacterial and antirheumatism agents are widely distributed in many medical plants and commonly used in clinical treatment. Therefore, the development of effective separation methods for the quality control of herbal medicines is absolutely important. In this article, the separation methods for the analysis of antibacterial and antirheumatism compounds in TOM were reviewed, including thin layer chromatography (TLC), gas chromatography (GC), supercritical fluid chromatography (SFC), high-performance liquid chromatography (HPLC), capillary electrophoresis (CE) and related hyphenation techniques. Sample preparation procedures and further development of these methods were also discussed.     

Screening and design of anti-diabetic compounds sourced from the leaves of neem (Azadirachta indica)

Diabetes Mellitus is affecting people of all age groups worldwide. Many synthetic medicines available for type 2 diabetes mellitus in the market. However, there is a strong requirement for the development of better anti-diabetes compounds sourced especially from natural sources like medicinal plants. The extracts from the leaves of neem (Azadirachta indica) is traditionally known to have anti-diabetes properties. Therefore, there is an increased interest to identify potential compounds identified from neem leaf extracts showing predicted binding property with the known diabetes mellitus type 2 protein enzyme target phosphoenol-pyruvate carboxykinase(PEPCK). The structure data for compounds found in the leaf extract of neem was screened against PEPCK using molecular docking simulation and screening techniques. Results show that the compound 3-Deacetyl-3-cinnamoyl-azadirachtin possesses best binding properties with PEPCK. This observation finds application for further consideration in in vitro and in vivo validation.     

Phytochemical and biological studies of Abies species

In the present review, the literature data on the phytochemical and biological investigations on the genus of Abies are summarized with 110 references. Up to now, 277 compounds were isolated from 19 plants of Abies species. The chemical constituents are mostly terpenoids, flavonoids, and lignans, together with minor constituents of phenols, steroids, and others. The crude extracts and metabolites have been found to possess various bioactivities including insect juvenile hormone, antitumor, antimicrobial, anti-ulcerogenic, anti-inflammatory, antihypertensive, antitussive, and CNS (central nervous system) activities.     

Anti-Helicobacter pylori activities of six Iranian plants

BACKGROUND: Helicobacter pylori is the major worldwide cause of bacterial gastrointestinal infections in adults and children. Antibiotic therapy and a combination of two or three drugs have been widely used to eradicate these infections. However, development of drug resistance in bacteria calls for new sources of drugs, and plants seem to be a logical source of new antibacterial compounds. METHODS: The anti-H. pylori activities of six native Iranian plants (Glycyrrhiza aspera, Juglans regia, Ligustrum vulgare, Thymus kotschyanus, Trachyspermum copticum and Xanthium brasilicum) and seven antibiotics were determined against 70 clinical isolates from children using the disk susceptibility assay. Minimum inhibitory concentrations were also measured for the biologically active extracts. One extract with the best anti-H. pylori activity was fractionated by silica gel and thin layer chromatography and the active compounds were identified by hydrogen nuclear magnetic resonance ((1)HNMR) spectroscopy. RESULTS: All plant extracts showed anti-H. pylori activity by the disk sensitivity method, but the most active extracts were those from X. brasilicum and T. copticum. In fact, the anti-H. pylori activities of the two extracts were superior to the disk antibiotic susceptibility profile. Minimum inhibitory concentrations were within the range of 31.25-250 micro g/ml. Fractionation and chemical identification of the extract from X. brasilicum showed the presence of two substances, a flavonoid and a xanthanolide. CONCLUSIONS: Due to the rise in antibiotic resistance, new sources of anti-H. pylori drugs are needed. The use of medicinal plants and/or their chemical components may have potential benefit in eradicating such problems.     

Antiulcerogenic activity of crude extract, fractions and populnoic acid isolated from Austroplenckia populnea (Celastraceae)

Many plant crude extracts and their isolated compounds are the most attractive sources of new drugs and show promising results for the treatment of gastric ulcers. Austroplenckia populnea is commonly known as "marmelinho-do campo, mangabeira-brava, mangabarana and vime" and it has been used in folk medicine as anti-dysenteric and anti-rheumatic. Powdered bark wood (3.25 kg) was macerated with aqueous ethanol (96%) and the extract was concentrated under reduced pressure to yield 406 g of crude hydralcoholic extract. The hydralcoholic extract was suspended in aqueous methanol and partitioned with hexane, chloroform and ethyl acetate (EtOAc) in sequence, yielding 8.0 g, 9.5 g and 98.17 g of crude extracts, respectively. Chromatography of the hexane extract over a silica gel column led to the isolation of the triterpene populnoic acid. The oral administration of hydralcoholic, hexane, chloroform and EtOAc extracts (200 mg/kg) decreased the ulcer lesion index (ULI) by 83.15%, 46.87%, 32.2%, 68.12%, respectively. Oral administration of populnoic acid (100 mg/kg) diminished the ULI by 55.29%. All the obtained results were significant in comparison with the negative control, with exception of the chloroform extract.     

In vitro Antioxidant and Anti‐inflammatory Activities of Extracts from Nicotiana tabacum L. (Solanaceae) Leafy Galls Induced by Rhodococcus fascians

Plant galls are widely distributed, and their extracts are used in traditional medicine worldwide. Traditional remedies containing extracts of plant galls in China, India and some African countries have effective in the treatment of various pathologies. To open a new promising procedure for screening bioactive compounds from plant galls, standardized plant materials were generated in vitro and used for phytochemical and biological investigations. Methanol aqueous chloroform and hexane extracts of Nicotiana tabacum leafy galls induced by Rhodococcus fascians were used to evaluate phenolic and flavonoid contents, and to investigate antioxidant activity by 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging and ferric reducing antioxidant/power assays and anti‐inflammatory activity by the lipoxygenase inhibition assay. Infection by R. fascians modifies significantly the phytochemical profile of N. tabacum as well as its biological properties. The total polyphenolic content was increased (120–307%), and that of flavonoids was reduced (20–42.5%). Consequently, antioxidant and anti‐inflammatory activities of non‐infected tobacco extracts are significantly modified compared to plants treated with leafy gall extracts. This shows that infection by R. fascians favoured the production of anti‐inflammatory and antioxidant compounds in N. tabacum. The study indicates the benefit of plant galls used in traditional medicines against various pathologies.