Molecular phylogenetics as a predictive tool in plant-based drug discovery in the genus Euphorbia L.

Recent estimates indicate that every fifth plant species on earth is threatened with extinction [1]. Thus, systematic methodologies for plant-based drug discovery are urgently needed. In the past, there have roughly been three approaches to drug discovery from plants: i) random screening ii) ethnomedicinal guided and iii) taxonomy/phylogeny guided approaches [2]. However, those approaches show limitations regarding time-efficiency and coverage. In recent years, medicinal plant uses have been proposed as proxy for bioactivity, and phylogenetic patterns in medicinal plant uses have suggested predictive power of molecular phylogenetics in drug discovery [3]. Here we investigate whether molecular phylogenetics can guide plant-based drug discovery using the cosmopolitan and pharmaceutically highly relevant genus Euphorbia L. [4,5] as an example. We highlight the importance of plant medicinal use categories in identifying phylogenetic patterns. Instead of grouping medicinal uses of Euphorbia into standardized categories, we propose a classification based on a biological response provoked by the treatment. We show that compared to the standardized categories a higher number and phylogenetically more diverse species are highlighted with potential for drug discovery [6]. High-resolution bioactivity profiling combined with high-performance liquid chromatography – high-resolution mass spectrometry – solid-phase extraction – nuclear magnetic resonance spectroscopy (HR-bioassay/HPLC-HRMS-SPE-NMR), allows for simultaneous chemical profiling and bioactivity testing of individual compounds in crude plant extracts [7]. In this presentation, we furthermore illustrate how our approach will be tested in the laboratory in future studies. In conclusion, this may allow for a more targeted and time-efficient approach in identifying drug candidates from plants.

Acknowledgements: This work was supported by the Marie Curie Actions of the 7th European Community Framework Programme: FP7/2007 – 2013/, REA grant agreement n° 606895-MedPlant to NR and PIEF-GA-2012 – 328637-BiodiversityAltitude to CHSL and NR. No financial support was received from LEO Pharma A/S. Arife Önder and Lene Torp-Milojevic are acknowledged for technical assistance. Martin Aarseth-Hansen and Gry Bastholm are acknowledged for assistance with collecting plant material.

Keywords: Euphorbia, phylogenetic prediction, drug discovery, medicinal plant use classification, HPLC-HRMS-SPE-NMR.

References:

[1] Plants under pressure – a global assessment. IUCN Sampled Red List Index for Plants. Kew: Royal Botanic Gardens; 2012.

[2] Balandrin MF, Kinghorn AD, Farnsworth NR. Plant-derived natural products in drug discovery and development. In: Kinghorn AD, Balandrin MF, editors. Human Medicinal Agents from Plants, volume 534. American Chemical Society; 1993: 2 – 12

[3] Saslis-Lagoudakis CH, Savolainen V, Williamson EM, Forest F, Wagstaff SJ, Baral SR, Watson MF, Pendry CA, Hawkins JA. Phylogenies reveal predictive power of traditional medicine in bioprospecting. Proc Natl Acad Sci USA 2012; 109: 15835 – 15840

[4] Horn JW, Van Ee BW, Morawetz JJ, Riina R, Steinmann VW, Berry PE, Wurdack KJ. Phylogenetics and the evolution of major structural characters in the giant genus Euphorbia L. (Euphorbiaceae). Mol Phylogenet Evol 2012; 63: 305 – 326

[5] Ernst M, Grace OM, Saslis-Lagoudakis CH, Nilsson N, Simonsen HT, Rønsted N. Global medicinal uses of Euphorbia L. (Euphorbiaceae). J Ethnopharmacol 2015; 176: 90 – 101

[6] Ernst M, Saslis-Lagoudakis CH, Grace OM, Nilsson N, Simonsen HT, Horn JW, Rønsted N. Evolutionary predicition of medicinal properties: drug discovery in the genus Euphorbia L. Under review Sci Rep

[7] Wubshet SG, Nyberg NT, Tejesvi MV, Pirttilä AM, Kajula M, Mattila S, Staerk D. Targeting high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance analysis with high-resolution radical scavenging profiles – bioactive secondary metabolites from the endophytic fungus Penicillium namyslowskii. J Chromatogr A 2013; 1302: 34 – 39

 

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