R. Verpoorte

Department of Pharmacognosy, Section Metabolomics, Institute of Biology Leiden,

PO Box 9502, 2300RA Leiden, The Netherlands

Email: VERPOORT@LACDR.LeidenUniv.NL

Abstract

Since ancient times mankind has exploited nature for all kind of useful products and enjoyed the colors, flavors, and fragrances of flowers, food, etc. Presently, many fine chemicals are derived from plants and used as medicines, dyes, flavors, fragrances, insecticides, etc. Originally most drugs were derived from plants, however, after the first successful introduction of synthetic drugs such as aspirin about 100 years ago, gradually synthesis became the more important source for drug development. Only in case of antibiotics and antitumor compounds, nature remained a major source for new drugs. Major reason was the difficulty of finding the active compounds in crude plant extracts, assays using animal experiments for testing activity are not suited for rapid bioassay guided fractionation of extracts. The assays for the antibiotic and antitumor activity on the other hand are more suitable for this purpose, explaining the success of natural products in these fields. In the past years the development of assays on the level of molecules (receptor binding and enzyme inhibition) opened complete new perspectives for natural products as source for new drugs. High throughput screens now allow the testing of thousands of samples per day. In combination with efficient separation methods and powerful spectrometric methods for identification and structure elucidation, active compounds from natural sources can rapidly be identified. Despite the rapid developments in drug discovery, the core of western medicine is still based on compounds from medicinal plants traditionally used in the Europe. About 120 plant derived compounds are used as such in western medicine, but also many synthetic analogues have been made such as analgesics based on morphine, and local anaesthetics based on cocaine.

Despite the importance of western medicine, presently about 80% of the world population is using medicinal plants as their major source for medication in primary health care. In most cases scientifically little is known about the activity of these medicinal plants. It is obvious that much can be learned from these traditional medicines. To explore and eventually exploit the enormous potential of the traditional knowledge different approaches can be used. First of all the already mentioned fast screening methods with known molecular targets can be used. However, it cannot be excluded that the activity of medicinal plants is due to synergistic effects of compounds present in the plant, or even due to compounds that are formed after digesting the plant material, either by biotransformations (both chemical and microbial) occurring in the digestive tract or in the liver. The willow bark is a good example. It contains salicoside that in the body is converted to salicylic acid, the compound responsible for the analgesic effect of this traditional medicine. Studies on traditional medicines thus require a new approach to understand their activity and eventually develop novel medicines. The systems biology approach that will be discussed in another presentation is such a very promising approach that will be very helpful in establishing the efficacy of medicinal plants and may lead to novel drugs.