A Perspective on Missing Aspects in Ongoing Purification Research towards Melissa officinalis

Melissa officinalis L. is a medicinal plant used worldwide for ethno-medical purposes. Today, it is grown everywhere; while it is known to originate from Southern Europe, it is now found around the world, from North America to New Zealand. The biological properties of this medicinal plant are mainly related to its high content of phytochemical (bioactive) compounds, such as flavonoids, polyphenolic compounds, aldehydes, glycosides and terpenes, among many other groups of substances. Among the main biological activities associated with this plant are antimicrobial activity (against fungi and bacteria), and antispasmodic, antioxidant and insomnia properties. Today, this plant is still used by society (as a natural medicine) to alleviate many other illnesses and symptoms. Therefore, in this perspective, we provide an update on the phytochemical profiling analysis of this plant, as well as the relationships of specific biological and pharmacological effects of specific phytochemicals. Currently, among the organic solvents, ethanol reveals the highest effectiveness for the solvent extraction of precious components (mainly rosmarinic acid). Additionally, our attention is devoted to current developments in the extraction and fractionation of the phytochemicals of M. officinalis, highlighting the ongoing progress of the main strategies that the research community has employed. Finally, after analyzing the literature, we suggest potential perspectives in the field of sustainable extraction and purification of the phytochemical present in the plant. For instance, some research gaps concern the application of cavitation-assisted extraction processes, which can effectively enhance mass transfer while reducing the particle size of the extracted material in situ. Meanwhile, membrane-assisted processes could be useful in the fractionation and purification of obtained extracts. On the other hand, further studies should include the application of ionic liquids and deep eutectic solvents (DES), including DESs of natural origin (NADES) and hydrophobic DESs (hDES), as extraction or fractionating solvents, along with new possibilities for effective extraction related to DESs formed in situ, assisted by mechanical mixing (mechanochemistry-based approach).