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Classical pharmacology has been the basis for the discovery of new chemical entities with therapeutic effects for decades. In natural product research, compounds are generally tested in vivo only after full in vitro characterization. However drug screening using this methodology is expensive, time-consuming and very often inefficient. Reverse pharmacology, also called bedside-to-bench, is a research approach based on the traditional knowledge and relates to reversing the classical laboratory to clinic pathway to a clinic to laboratory practice. It is a trans-disciplinary approach focused on traditional knowledge, experimental observations and clinical experiences. This paper is an overview of the reverse pharmacology approach applied to the decoction of Argemone mexicana, used as an antimalarial traditional medicine in Mali. A. mexicana appeared as the most effective traditional medicine for the treatment of uncomplicated falciparum malaria in Mali, and the clinical efficacy of the decoction was comparable to artesunate–amodiaquine as previously published. Four stages of the reverse pharmacology process will be described here with a special emphasis on the results for stage 4. Briefly, allocryptopine, protopine and berberine were isolated through bioguided fractionation, and had their identity confirmed by spectroscopic analysis. The three alkaloids showed antiparasitic activity in vitro, of which allocryptopine and protopine were selective towards Plasmodium falciparum. Furthermore, the amount of the three active alkaloids in the decoction was determined by quantitative NMR, and preliminary in vivo assays were conducted. On the basis of these results, the reverse pharmacology approach is discussed and further pharmacokinetic studies appear to be necessary in order to determine whether these alkaloids can be considered as phytochemical markers for quality control and standardization of an improved traditional medicine made with this plant.

Polygonum cuspidatum Sieb. and Zucc. has been traditionally used as a member of many anti-inflammatory polyherbal formulations, but is now a widespread invasive neophyte in Europe and America. To discuss if the invasive variety is chemically identical to the native one in traditional medicine, the different constituents of the invasive variety compared to the native variety were isolated and their anti-inflammatory activity was tested. Resveratroloside and catechin-(4α→8)-catechin, the newly found constituents in the invasive variety, have similar nitric oxide (NO) inhibition potency as that of piceid (the major constituent of P. cuspidatum), but the newly found major constituent, i.e., piceatannol glucoside, showed no apparent effect. On the other hand, as a marker, the total content of resveratrol in the methanol root extract after glucosidase hydrolysis was measured and compared between the invasive and native varieties. The total content of resveratrol measured in the root extracts of the Swiss sample was about 2.5 times less than that of the Chinese one. This study brings attention to the point that when the invasive variety of P. cuspidatum is used in traditional medicine, the chemical difference should be kept in mind.

A new flavanone-chromone biflavonoid, preussianone (1), has been isolated from the leaves of Garcinia preussii, along with four known biflavonoids. The absolute stereostructures were elucidated by chemical, spectroscopic, and chiroptical methods. The biological properties of the new biflavonoid against several bacterial strains were evaluated.

Plants have a rich history as medicines for human use. Recently introduced plant-derived drugs include paclitaxel from Taxus (Taxaceae) species for the treatment of cancers, artemisinin for malaria therapy and the alkaloid galanthamine for the management of Alzheimer's disease. A judicious combination of chemical and biological screening techniques can provide a steady supply of lead compounds for the improved treatment of human ailments. By this means, candidate compounds can be rapidly selected for further development, as is the case for xanthones from gentians and coumarins from Peucedanum ostruthium (Apiaceae), which may be of relevance in Alzheimer's disease. Encouraging results are also being obtained for hypericin from Hypericum perforatum (Hypericaceae) in the photodynamic therapy of cancer. An aspect that must not be forgotten is that the usual biological screening procedures do not pick up prodrugs which have to be metabolized by the human body into active analogues. A good example is salicin from Salix species (Salicaceae) which is metabolized in the body to give the anti-inflammatory and analgesic compound salicylic acid. Investigations which include simulation of metabolism are thus of primordial importance.

Different natural products from the plant kingdom including isoflavones, prenylflavones, coumestans, stilbenes, and lignans can cause endocrine perturbations, especially on the estrogenic hormonal pathway because of their structural analogies to estradiol. Several studies report the presence of such compounds in food, the richest source being soy and soy products. These substances, commonly called phytoestrogens, are known to influence the human hormonal profile and soy preparations are being considered for use as post-menopausal estrogen replacement therapy. Numerous clinical and epidemiological reports have studied the influence of phytoestrogens on the development of hormone-dependent cancers. The effect on genital development of postnatal phytoestrogen exposure is still under debate. Consumption of phytoestrogens may also influence the incidence of bone diseases, atherosclerosis, or Alzheimer's disease. This article summarizes the classification of phytoestrogens, their pharmacological evaluation and properties, and the methods used for their identification.

Plants represent an extraordinary reservoir of novel molecules and there is currently a resurgence of interest in the vegetable kingdom as a provider of new lead compounds for introduction into therapeutic screening programs. Plant constituents of interest are usually isolated following a bioactivity-guided fractionation procedure. In order to render this approach more rapid and efficient, the dereplication of crude plant extracts with LC-hyphenated techniques (LC/UV-DAD, LC/MS and LC/NMR) represents a strategic element to avoid finding known constituents and to target the isolation of new bioactive compounds. The development of simple and rapid bioassays is also crucial for an efficient localisation of active principles. In this respect, the use of bioautographic methods, which enable a direct screening of bioactive constituents on TLC is of great interest. The combination of chemical and biological screening has proved to be very efficient for the survey of an important number of extracts and for the discovery of new lead compounds and several examples of this approach will be discussed in this paper.

Higher plants represent a rich source of new molecules with pharmacological properties, which could become lead compounds for the development of new drug products. During the last decades, the renewed interest in investigating natural substances has led to the introduction of several important drugs, such as the anticancer substances vinblastine, vincristine, taxol and camptothecine derivatives, or the antimalarial agent artemisinin. Despite recent scientific and technological advances, parasitic diseases continue to affect millions of people in both tropical and subtropical zones of the world. On the other hand the drugs used for the treatment of most parasitic diseases are extremely limited. In this field, natural products constitute a reservoir of new molecules with potential therapeutic interest. An outline is presented here of some important results obtained by the Laboratory of Pharmacognosy and Phytochemistry of the University of Geneva on plants used to treat some of the neglected diseases. The strategy employed for the study of these plants is outlined, covering all aspects from the selection of plant material to the isolation of the active substances. Different bioactivities have been investigated such as the search for new molluscicidal and larvicidal agents. Results are also included for antileishimanial and antimalarial compounds.

Higher plants represent a rich source of new molecules with pharmacological properties, which are lead compounds for the development of new drugs. During the last decades, the renewed interest in investigating natural products has led to the advent of several important drugs, such as the anticancer substances vinblastine, vincristine and taxol, or the antimalarial agent artemisinin. Success in natural products reasearch is conditioned by a careful plant selection, based on various criteria such as chemotaxonomic data, information from traditional medicine, field observations or even random collection. One main strategy in the isolation of new leads consists of the so-called bioactivity-guided isolation, in which pharmacological or biological assays are used to target the isolation of bioactive compounds. One major drawback of this strategy is the frequent isolation of known metabolites. Therefore, hyphenated techniques (LC-UV/DAD, LC-MS, LC-NMR) have been developed, in order to detect as early as possible potential original structures. These compounds can then be tested in various bioassays. Using a combination of hyphenated techniques and bioactivity-guided isolation procedures, a series of new diterpenoic antifungal quinones have been isolated from the African tree, Bobgunnia madagascariensis (Leguminosae) and recently patented for their strong activity and for their potential use in the treatment of systemic mycoses.

The plant kingdom is still an untapped reservoir of new molecules with therapeutic potential. A selection of bioactive plant constituents recently discovered are presented with focus on new drugs or lead compounds in an advanced state of development. Obtaining pure new biologically active substances from plants remains a complex task. Biological and chemical screenings are complementary approaches for the rapid detection and isolation of new interesting plant constituents. Biological screening followed by activity-guided fractionation has been successfully used in our laboratories for the discovery of new antifungal metabolites and inhibitors of enzymes involved in the aetiology of prostate hyperplasia. High-performance liquid chromatography (HPLC) coupled to UV spectroscopy (LC/UV), mass spectrometry (LC/MS), and magnetic resonance (LC/NMR) proved to be highly efficient for the chemical screening of crude plant extracts. These hyphenated techniques were extensively used for the investigation of polyphenols with monoamine-oxidase inhibitory (IMAO) properties in Gentianaceae species.

The plant kingdom is still an untapped reservoir of new molecules with therapeutic potential. A selection of bioactive plant constituents recently discovered are presented with focus on new drugs or lead compounds in an advanced state of development. Obtaining pure new biologically active substances from plants remains a complex task. Biological and chemical screenings are complementary approaches for the rapid detection and isolation of new interesting plant constituents. Biological screening followed by activity-guided fractionation has been successfully used in our laboratories for the discovery of new antifungal metabolites and inhibitors of enzymes involved in the aetiology of prostate hyperplasia. High-performance liquid chromatography (HPLC) coupled to UV spectroscopy (LC/UV), mass spectrometry (LC/MS), and magnetic resonance (LC/NMR) proved to be highly efficient for the chemical screening of crude plant extracts. These hyphenated techniques were extensively used for the investigation of polyphenols with monoamine-oxidase inhibitory (IMAO) properties in Gentianaceae species.