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Metabolomics, nature and drug discovery

Drug discovery is the process which aims at the identification of molecules that have a potential to become therapeutic agents (1). Nowadays, there are multiple approaches to discover a drug like computer based or combinatorial chemistry. Nevertheless, natural sources, such as plants, were the first source of novel pharmacological compounds, and even during this century, natural products still have a significant presence in drug development. Molecules in nature can act not only as a direct active compound, but also as scaffolds or skeletons for new synthetic compounds, and offer wide and multiple options to explore new biological functions. (2)

It is important to mention that plants have a huge content of different compounds called metabolites, molecules produced during the metabolism that are important for the plant survival and that can be of pharmacological interest. The metabolite composition changes according to the part of the plant (flower, roots, leaves) and the environmental factors (light, temperature, water) (3). Essential oils, for instance, are liquid extracts from plants, and have around 200-300 kinds of metabolites (4)(5) that can be both volatile and non-volatile molecules. Due to this high content of compounds, it is extremely important to identify the metabolite responsible for the action we are looking for, it is not as simple as crushing and mixing the plant to get the biological effect. In fact, some of the metabolites are considered allergens; it can be dangerous to use the whole content (even if it is natural). The diversity and high concentration of molecules offer a huge opportunity for research, but also are responsible for the irritation or burns in skin if we apply the essential oil undiluted (6). For a pharmacological effect we always need to take into account the molecule (just one) and the dose. Morphine and salicylic acid are examples of biological active metabolites present in plants.

In order to isolate one metabolite from a plant, it is fundamental to know its chemical properties, and according to them select the type of extraction. Extraction methods include solvent extraction, pressing, sublimation and distillation. The most widely used is solvent extraction, where the choice of the right solvent or solvents is key for an effective and selective obtention. The polarity of the solvent must be similar to the metabolite, polar solvents for polar metabolites and nonpolar solvents for nonpolar metabolites, in some cases more than one solvent extraction is needed for the isolation. After the extraction, it is necessary to do a characterization to be sure that the compound we got is actually the one we wanted. One big challenge in the process is that some metabolites can be difficult to purify or present in extremely low concentration in the plant, resulting in a low percent yield.

The new computational methods that have arisen at the end of the last century and during this one, added to the fact that metabolites tend to be difficult to isolate and identify (increasing the price and time), caused a diminution in the use of natural products for drug discovery (7). Nevertheless, in the last decade, metabolomics has arrived as a tool for the study of complex mixtures, such as phytochemical preparations and essential oils. This technique consists in the qualitative and quantitative analysis of thousands of metabolites at the same time (8) using analytical methods like gas and liquid chromatography-mass spectrometry or nuclear magnetic resonance spectroscopy (NMR). Metabolomics makes the research more efficient and cheaper, and allows identifying even slight changes in the plant’s metabolome due to stress factors or climate conditions. This technology is not only useful in phytochemistry, but also in medicine, the presence of certain metabolites in our body can act as biomarkers for a specific disease.

Plants have been an important source of bioactive metabolites throughout history, they present a great chemical diversity which still today offers a huge opportunity for pharmacological research. This huge variety of compounds also makes the identification of the active metabolite key in the process, and is not always easy. In the last decades, the use of natural products in drug discovery has decreased, and the arrival of new technologies and new approaches in drug discovery have appeared. Metabolomics, an effective analytical tool has also emerged, and can act as the link between the traditional and the modern, it allows to combine the varied and unique molecules in nature with the efficiency of innovative technologies.


  1. Drug development, an overview | ScienceDirect Topics. Retrieved April 5, 2022, from:

  2. Veeresham, C. (2012). Natural products derived from plants as a source of drugs. In Journal of Advanced Pharmaceutical Technology & Research (Vol. 3, Issue 4, p. 200). Medknow.

  3. Yang, L., Wen, K.-S., Ruan, X., Zhao, Y.-X., Wei, F., & Wang, Q. (2018). Response of Plant Secondary Metabolites to Environmental Factors. In Molecules (Vol. 23, Issue 4, p. 762). MDPI AG.

  4. Dhifi, W., Bellili, S., Jazi, S., Bahloul, N., & Mnif, W. (2016). Essential Oils’ Chemical Characterization and Investigation of Some Biological Activities: A Critical Review. In Medicines (Vol. 3, Issue 4, p. 25). MDPI AG.

  5. Aziz, Z. A. A., Ahmad, A., Setapar, S. H. M., Karakucuk, A., Azim, M. M., Lokhat, D., Rafatullah, Mohd., Ganash, M., Kamal, M. A., & Ashraf, G. M. (2018). Essential Oils: Extraction Techniques, Pharmaceutical And Therapeutic Potential - A Review. In Current Drug Metabolism (Vol. 19, Issue 13, pp. 1100–1110). Bentham Science Publishers Ltd.

  6. “Essential Oils – Health Warning.” Healthy Western Australians, Department of Health,

  7. Feyaerts, A. F., Luyten, W., & Van Dijck, P. (2020, February 18). Striking essential oil: Tapping into a largely unexplored source for drug discovery. Nature News. Retrieved April 4, 2022, from

  8. Yuliana, N. D., Khatib, A., Choi, Y. H., & Verpoorte, R. (2011). Metabolomics for bioactivity assessment of natural products. In Phytotherapy Research (Vol. 25, Issue 2, pp. 157–169). Wiley.

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