Phylogenies reveal predictive power of traditional medicine in bioprospecting

Abstract

There is controversy about whether traditional medicine can guide drug discovery, and investment in bioprospecting informed by ethnobotanical data has fluctuated. One view is that traditionally used medicinal plants are not necessarily efficacious and there are no robust methods for distinguishing those which are most likely to be bioactive when selecting species for further testing. Here, we reconstruct a genus-level molecular phylogenetic tree representing the 20,000 species found in the floras of three disparate biodiversity hotspots: Nepal, New Zealand, and the Cape of South Africa. Borrowing phylogenetic methods from community ecology, we reveal significant clustering of the 1,500 traditionally used species, and provide a direct measure of the relatedness of the three medicinal floras. We demonstrate shared phylogenetic patterns across the floras: related plants from these regions are used to treat medical conditions in the same therapeutic areas. This finding strongly indicates independent discovery of plant efficacy, an interpretation corroborated by the presence of a significantly greater proportion of known bioactive species in these plant groups than in random samples. We conclude that phylogenetic cross-cultural comparisons can focus screening efforts on a subset of traditionally used plants that are richer in bioactive compounds, and could revitalize the use of traditional knowledge in bioprospecting.ethnobotany | ethnopharmacology | herbal medicine | phylogeny | systematics M any pharmaceutical drugs are derived from plants that were first used in traditional systems of medicine (1), and according to the World Health Organization ∼25% of medicines are plant-derived (http://www.who.int/mediacentre/factsheets/ fs134). Discoveries of novel molecules and advances in production of plant-based products (2, 3) have revived interest in natural product research. Traditional knowledge has proven a useful tool in the search for new plant-based medicines (4-8). The number of traditionally used plant species worldwide is estimated to be between 10,000 and 53,000 (9, 10); however, only a small proportion have been screened for biological activity (11,12) and the plants from some regions are less studied than others. For example, only 1% of tropical floras have been investigated (12). Moreover, there has been no systematic study to determine whether traditionally used species are significantly more likely to yield valuable bioactive compounds. This lack of data creates controversy about whether traditional medicine can guide drug discovery (1,11,(13)(14)(15), and investment in ethnobotanically led bioprospecting has fluctuated (5, 14, 15). Methods put forward for distinguishing those plants most likely to be bioactive when selecting species for further testing have been criticized, and criteria proposed to prioritize traditionally used species have not been rigorously tested (16,17). For example, use of the same or related plants by people from different regions and cultures provides indirect evidence for bioactiv...

Tanshinone IIA Exhibits Anticonvulsant Activity in Zebrafish and Mouse Seizure Models

“…According to the World Health Organization (WHO), 70−80% of the population in developing and developed countries have used, or depend on such therapies, which became the impetus for efforts in bioprospecting and drug development. 2 Despite prevalent skepticism, as many as 25% of pharmaceutical drugs on the market are plant-based and were discovered through investigations on traditional or folk medicine practiced by different cultures. 1,2 The rationale behind this approach in drug discovery is that small molecules isolated or derived from natural sources offer a more diverse set of structures compared with compounds synthesized through medicinal chemistry or combinatorial techniques.…”

“…2 Despite prevalent skepticism, as many as 25% of pharmaceutical drugs on the market are plant-based and were discovered through investigations on traditional or folk medicine practiced by different cultures. 1,2 The rationale behind this approach in drug discovery is that small molecules isolated or derived from natural sources offer a more diverse set of structures compared with compounds synthesized through medicinal chemistry or combinatorial techniques. 2 Each plant or marine extract can be treated as a library potential of hits, which can be screened using an appropriate medium-to high-throughput in vivo model such as zebrafish (Danio rerio), a freshwater teleost of the Cyprinidae family.…”

“…1,2 The rationale behind this approach in drug discovery is that small molecules isolated or derived from natural sources offer a more diverse set of structures compared with compounds synthesized through medicinal chemistry or combinatorial techniques. 2 Each plant or marine extract can be treated as a library potential of hits, which can be screened using an appropriate medium-to high-throughput in vivo model such as zebrafish (Danio rerio), a freshwater teleost of the Cyprinidae family. 3,4 In screening for potential hits and leads for AED development, we have previously described the use of larval zebrafish as a platform for pinpointing AED-like activity of small molecules isolated from plant sources.…”

Biodiversity only makes sense in the light of evolution

“…Using a genus-level phylogenetic tree representing 20,000 species from three unrelated floras (Nepal, New Zealand, and the Cape of South Africa), it was shown that the 1500 species used in traditional medicine in the three regions are clustered in the phylogeny. In other words, related plants from the three regions are used to treat similar medical conditions, indicating that the same medical component of these plants was independently discovered (Saslis-Lagoudakisa et al 2012). These examples only represent a small fraction of the questions in biodiversity science that can be studied using evolutionary approaches.…”

Reaffirming ‘Ethnobotanical Convergence’

“…This convergent use is likely due to similar chemical composition, implying a similar flavour and ultimately, similar bioactivity, so people would select both taxa for similar purposes. As Hawkins and Teixidor-Toneu [1] mention, linguistic isolation suggests independent but convergent plant discovery and management [10], and the western and eastern Mediterranean cultures in the above example were linguistically isolated (but are no longer due to globalisation). Manousheh in Lebanon (Eastern Mediterranean) is currently seasoned with Origanum syriacum L. (called zaatar in Arabic and thym, the standard name for the genus Thymus, in French) collected in the wild, whereas western pizza is seasoned in the same place with a cultivated species of Origanum (probably O. vulgare L.) purchased in the commerce, called origan (the standard name for the genus Origanum) in French and lacking an Arabic name (M. Bou-Dagher Kharrat, pers.…”