Medicinal plants heading for new drugs

Powerful substances in Madagascar periwinkle (Catharanthus roseus), willow tree (Salix spp) and Pacific yew (Taxus brevifolia) cure serious and common diseases. Montage by Gorm Palmgren

Humans have used wild plants for traditional medicine since our earliest civilization, and the number of plant species used for this purpose is in the range of 10,000 to 53,000 – an astonishing number considering that nature ‘only’ counts around 400,000 plant species in total. The healing power is caused by a myriad of chemical substances, which plants produce to enhance their own survival – eg to deter herbivory insects or inhibit growth of competing plants. By some people, these chemicals are highly praised as natural, unblemished by vicious pharmaceutical companies and opposed to poisonous, man-made pills created with profits in mind.

Obviously, the frontiers cannot be drawn so sharply and the fact is that according to WHO around 25% of existing medicine is derived from plants. Only a tiny fraction of the plants used in traditional medicine have, however, been screened for biological activity and thus there remains a substantial hidden potential for designing new drugs by screening the remainder. Given the huge number of candidate plant species and the large number – in the hundreds – of bioactive compounds each of them contains, this task might seem insurmountable. However, a new study recently published in PNAS shows how we can identify the most promising biomedical plants and thereby put traditional medicin back on track.

Medicinal plants used in three widely separated regions are highly related. Map by Google

C. Haris Saslis-Lagoudakis and Julie A. Hawkins from School of Biological Sciences, University of Reading in the United Kingdom approached the challenge by studying how potential candidates from different regions relate to each other. More specifically, they selected three biodiversity hotspots – Nepal, New Zealand, and the Cape of South Africa – and established phylogenetic trees of their 20,000 plant species. Around 1,500 of these are used in traditional medicine, and it turned out that they were not evenly spread out on all the twigs of the family tree. Instead, they clustered on relatively few branches, which contained 60% more medicinal plants than you would expect from chance.

At a first glance, it might not come as a surprise that plants with highly bioactive chemicals are related to each other, since the biochemistry is determined by their genetic makeup. But according to the authors it is a strong indication that the medical properties of traditionally used plants are real and not based on chance or superstition. In Nepal, eg, malaria is treated with two different plants – rushfoil (Croton) and physic nut (Jatropha) – that both belong to the family Euphorbiaceae, known for its many bioactive compunds. This suggests that potential drugs against malaria can be found among these plants and their relatives and that they might be worthwhile screening by pharmaceutical companies. Another strong indication that medicinal plants are for real is that related plant species are used to cure the same diseases in the three widely separated geographical regions.

Ready to drink macerated medicinal liquor with goji berry, tokay gecko, and ginseng, for sale at a traditional medicine market in Xi’an, China. From Wikipedia

As an example, digestive problems are commonly treated by jacket plum (Pappea in the Cape of South Africa, by heartseed (Cardiospermum) in Nepal and by the titoki tree (Alectryon) in New Zealand – three plants that all belong to the soapberry family (Sapindaceae). Along these lines, the study finds that there is a very strong agreement in medicinal plant lineages used in the three regions against diseases related to gastrointestinal, respiratory and fertility problems, as well as to muscular, neurological and skin diseases. Since these three regions are so distant and their floras so distinct, it seems evident that the biomedical properties of the plants were discovered independently and that their uses indicate a genuine effect against the diseases.

On the basis of their results, the authors propose a new and more sophisticated framework in order to identify plants that can be used as targets for development of new drugs based on traditional medicine. The candidate should be looked for in lineages that both have phylogenetic similarities and share cross-cultural usage. At present, less than 20% of the plants from these ‘hot branches’ have been screened by pharmaceutical companies.

Coca plant (Erythroxylum coca) and the molecular structure of cocaine (grey: carbon, blue: nitrogen, red: oxygen, white: hydrogen). Illustration by MPI for Chemical Ecology

The bioactive compounds that traditional healers and pharmaceutical companies are both looking for belong to the vast group of secondary metabolites – ie substances that are not essential building blocks or intermediates common to all plants, but rather biochemicals that are limited to a smaller group of plants and serve a specific function. Below is a non-exclusive list of medicinal chemicals from plants:

Example of medicinal chemicals from plants
Class Natural function Examples of medicinal use
Alkaloids: Contain an N-bearing ring Potent toxins against herbivores Vincrisine from Madagascar periwinkle (Catharanthus roseus) against leukaemia
Glycosides: A sugar bound to a non-carbohydrate moiety Inactive precursors of toxins Digoxin from foxglove (Digitalis lanata) against heart conditions(
Saponins: Amphipathic glycosides, often steroidal Anti-feedants and anti-microbial Mixture of triterpenoid saponins from baby’s breath Gypsophila paniculata) increase toxicity of anti-cancer drugs
Phenols: Containing one or more phenol rings Protect against infection and insect herbivores Salicylic acid derived from willow (Salix spp) against pain and inflammation