Ethnopharmacology and systems biology: A perfect holistic match

Abstract

Traditional medical doctors often apply a holistic approach in prescribing medicines to the patient. Each individual patient gets his own optimalized medicine, usually a mixture of different ingredients. The present day paradigm of drug development of <single target, single compound>, is based on a super reductionist approach which involves mostly tests of compounds at the molecular level in, e.g., receptor binding assays. This approach is not the best for studies on traditional medicines. A more holistic approach using systems biology seems much more suited to proof efficacy and to obtain information that might lead to understanding the mode of action. Synergy, prodrugs, novel targets, all these might be detected by a systems biology approach whereas the reductioinist approach only will recognize activity on already known targets, and will not detect synergism and prodrugs. Metabolomics will be a major tool in recognizing compounds connected with activity in the traditional medicines, and will also be very useful in recognizing the effect on the test organism, which can be the patient in case of clinical trials with well established traditional medicines.

Introduction

In 1979, I published my first paper in the Journal of Ethnopharmacology, which concerned the characterization of a toad venom by means of GC (Verpoorte et al., 1979). Being one of the authors of the first volume, I was asked to give my view on the future of ethnopharmacology. In my editorial to this volume I have already written some points. But I would like to write more extensively on my views on ethnopharmacology and particularly how I think pharmacognosy and phytochemistry can contribute to the further successful development of this field. With development I mean that we will be able to proof efficacy of traditional medicines to the benefit of all mankind.

Before doing so let me first go back to where I started my scientific career in the laboratories of Finn Sandberg in Sweden. He was very keen on studying the pharmacology of medicinal plants that he collected among others in Cameroon. First we screened the pharmacological activity by the Hippocratic screening (Malone and Robichaud, 1962). A test using whole animals, to which crude plant extracts were administered intraperitoneally, after which a whole set of observations was made during a given time period. The test was validated by injecting a series of known drugs. By comparing the observations made for these compounds with those obtained with the extracts, an indication about possible activities was obtained. Working with Strychnos species, we particularly focused on a strychnine like effect (convulsions) or curare (muscle relaxant) effect (Sandberg et al., 1971, Verpoorte and Bohlin, 1976). Subsequently we did bioassay guided fractionation to identify the active compounds.

It was during these studies that I became interested in the ethnopharmacological aspects of this research. Particularly the question how in ancient time people found the important drugs which still are the core of our pharmacotherapy. Curare may serve as an example. When the Indians moved into the Amazonian area, with some 50,000 different plant species around them, they picked out a few species (some Strychnos species and Chondodendron tomentosum) that served as the source for an arrow poison: curare. Deadly toxic when injected, but orally taken it is not toxic. Independently similar species where found in Central Africa, and possibly also in Malaysia (Bisset, 1989, Bisset, 1992). Even nowadays with the enormous potential of the high throughput screening methodology of the pharmaceutical industry, it would be a major project to screen all plants in the Amazonian rainforest to find these muscle-relaxant compounds. Most likely it will remain a mystery for ever how people found those plants. Though this drug development process may still go on with people living in remote areas, e.g. in case of new diseases. It would be interesting to see how people in areas with a high incidence of AIDS explore their environment for possible medicines.