15 July 2016

Medicinal properties of succulent plants

Olwen Grace, Research Leader in Comparative Plant and Fungal Biology, and PhD student Madeleine Ernst from the University of Copenhagen, discuss evolutionary studies of the medicinal value of succulent plants.

Princess of Wales Conservatory

Iconic succulent plants

Succulent plants possess specialised water-storing tissues that give them a unique ability to maintain photosynthesis and other metabolic processes during droughts. Not surprisingly, these water-storing plants are well adapted to arid and semi-arid deserts, and other habitats where plants experience regular water limitations – for instance due to overnight freezing (alpine habitats) or rain shadows (epiphytic tree canopies). 

The variety of succulent plants — thousands of species around the world, representing plant families throughout the angiosperm tree of life — makes them an ideal group for comparative studies of plant adaptations. 

The genera Aloe (Xanthorrhoeaceae) and Euphorbia (Euphorbiaceae) are two iconic succulent plant groups, each comprising hundreds of succulent species. Both genera are used in folk medicine and commercial therapeutic products. Indeed, Aloe vera is one of the most widely used plant species in the world today, while Euphorbia peplus (a non-succulent species) was used to develop Picato ®, a drug for treating a precancerous skin condition, marketed by the Danish pharmaceutical company LEO-Pharma.

We’re investigating the possibility that evolutionary relationships among the species used medicinally in both Aloe and Euphorbia could reveal a pattern that would allow us to predict other medicinally valuable species on a phylogeny for each genus. A phylogeny is a diagram showing the evolutionary relationships among species; here we used statistical analyses of DNA sequences to estimate these relationships.

Bright orange aloes
Aloe ferox in South Africa with iconic candle-like inflorescences. Credit RBG Kew/O. Grace.

Exploring the natural capital of Aloe

Aloes are emblematic plants of the African landscape, and are also found in Madagascar and the Arabian Peninsula. A single species, Aloe vera, supports an extensive international natural products industry. The question remains whether any of the 500 other species of Aloe share the traits for which Aloe vera is celebrated. We are pursuing this question in our research with colleagues from around the globe. This work is important because it could highlight opportunities for local species of Aloe to be used in natural product industries in Africa where the majority of Aloe species occur.

Research at Kew on the evolution of Aloe showed that these plants originated in southern Africa around 16 million years ago. From there, the genus reached its present-day distribution in two evolutionary ‘bursts’ across the African continent and on to Madagascar and the Arabian Peninsula. The phylogenetic information confirmed that Aloe vera is native to the Arabian Peninsula, solving a long-standing botanical mystery about its origins, and revealed that it is only distantly related to many older species in southern Africa.

When analysed together, the phylogeny and a large dataset of known uses of aloes showed that their medicinal uses, in particular, are not randomly distributed across the phylogeny. In other words, the “medicinality” of aloes appears to be clustered in certain groups of species. The main predictor for this clustering is the presence of large leaves with well-developed succulent tissue, implying that people favour succulence for medicine. Our next aim is to identify the species that are more closely related to Aloe vera and the traits that may have led to its selection over all the other available species. 

Strange green round inflorescence
Characteristic inflorescences known as cyathia on Euphorbia dregeana. Credit RBG Kew/O. Grace.

Medicinal potential of Euphorbia

With almost 2,000 species, Euphorbia is one of the largest genera of flowering plants on earth. The members of this genus are exceptionally variable in growth form and habitat, ranging from small herbs to trees and succulent shrubs, occurring from temperate to subtropical and tropical regions. All species of Euphorbia produce white latex and possess flower-like inflorescences, called cyathia. Four subgenera are recognised: Esula, Athymalus, Euphorbia and Chamaesyce. Subgenus Esula includes mainly small herbs growing in temperate Europe, whereas the succulent species that are often mistaken for cacti, are mostly represented in subgenera Athymalus and Euphorbia

Madeleine Ernst, a PhD student in Nina Rønsted’s group at the Natural History Museum of Denmark, has been researching the phylogenetic patterns in medicinal use of Euphorbia. She searched a total of 260 publications on the online repository, JSTOR, for records of Euphorbia's medicinal uses. She found that the exceptional diversity of the genus is not only limited to its growth forms and chemistry, but is also reflected in its many medicinal uses. Medicinal uses were identified for over 5% of the genus (about 100 species), with most citations referring to treatments of the digestive system, skin ailments and infections. The taxonomic distribution of the medicinal value shown by these uses also revealed that the subgenus Chamaesyce has been chemically under-investigated but is medicinally very valuable. Remarkably, almost 70% of all chemical studies to date focus on species of the European subgenus Esula and very few on the medicinally important subgenus Chamaesyce. A more detailed study of the medicinal traits of Euphorbia using a phylogeny found that Euphorbia species used to treat inflammation-related disorders are distributed all over the genus, with special concentration in subgenus Chamaesyce and Euphorbia.

The next step is to investigate whether the chemical or biological traits of the species are able to explain the variation in medicinality among the subgenera. The chemistry and bioactivity of more than 50 species of Euphorbia are now being analysed at the University of Copenhagen and LEO-Pharma A/S in Denmark, with the aim of investigating the complex relationships between chemistry, biological activity and medicinality. It remains to be seen whether succulence or other morphological or ecological traits play a major role in the medicinality of Euphorbia as is found in Aloe.

References

Dorsey, B.L., Haevermans, T., Aubriot, X., Morawetz, J.J., Riina, R., Steinmann, V.W. & Berry, P.E. (2013). Phylogenetics, morphological evolution, and classification of Euphorbia subgenus Euphorbia (Euphorbiaceae). TAXON 62: 291–315. Available online

Ernst, M., Grace, O.M., Saslis-Lagoudakis, C.H., Nilsson, N., Simonsen, H.T. & Rønsted, N. (2015). Global medicinal uses of Euphorbia L. (Euphorbiaceae). Journal of Ethnopharmacology 176: 90–101. Available online

Ernst, M., Saslis-Lagoudakis, C.H., Grace, O.M., Nilsson, N., Simonsen, H.T., Horn, J.W. & Rønsted, N. (2016). Evolutionary prediction of medicinal properties in the genus Euphorbia L. Scientific Reports 6: 30531. DOI:10.1038/srep30531. Available online

Grace, O.M., Buerki, S., Symonds, M.R.E., Forest, F., van Wyk, A.E., Smith, G.F., Klopper, R.R., Bjorå, C.S., Neale, S., Demissew, S., Simmonds, M.S.J. & Rønsted, N. (2015). Evolutionary history and leaf succulence as explanations for medicinal use in aloes and the global popularity of Aloe vera. BMC Evolutionary Biology 15: 29. Available online

Grace, O.M., Simmonds, M.S.J., Smith, G.F. & van Wyk, A.E. (2009). Documented utility and biocultural value in the genus Aloe L. (Asphodelaceae): a review. Economic Botany 63: 167–178. Available online

Horn, J.W., Xi, Z., Riina, R., Peirson, J.A., Yang, Y., Dorsey, B.L., Berry, P.E., Davis, C.C. & Wurdack, K.J. (2014). Evolutionary bursts in Euphorbia (Euphorbiaceae) are linked with photosynthetic pathway. Evolution 68: 3485–3504. Available online

Horn, J.W., van Ee, B.W., Morawetz, J.J., Riina, R., Steinmann, V.W., Berry, P.E. & Wurdack, K.J. (2012). Phylogenetics and the evolution of major structural characters in the giant genus Euphorbia L. (Euphorbiaceae). Molecular Phylogenetics and Evolution 63: 305–326. Available online

Peirson, J.A., Bruyns, P.V., Riina, R., Morawetz, J.J. & Berry, P. E. (2013). A molecular phylogeny and classification of the largely succulent and mainly African Euphorbia subg. Athymalus (Euphorbiaceae). TAXON 62: 1178–1199. Available online

Riina, R., Peirson, J.A., Geltman, D.V., Molero, J., Frajman, B., Pahlevani, A., Barres, L., Morawetz, J.J., Salmaki, Y., Zarre, S., Kryukov, A., Bruyns, P.V. & Berry, P.E. (2013). A worldwide molecular phylogeny and classification of the leafy spurges, Euphorbia subgenus Esula (Euphorbiaceae). TAXON 62: 316–342. Available online

Yang, Y., Riina, R., Morawetz, J.J., Haevermans, T., Aubriot, X. & Berry, P.E. (2012). Molecular phylogenetics and classification of Euphorbia subgenus Chamaesyce (Euphorbiaceae). TAXON 61: 764–789. Available online

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