A trip in voice phytotheraphy: TRPA1 ion channel as a target for bioactive compounds in herbal remedies for voice care

Voice is the sound we produce to communicate meanings and ideas and has a capital importance in human social development. Herbs have been used for voice care since ancient times and many herbal remedies are still in use, both as folk medicine and as sources of botanicals used in commercial products. In Europe Sisymbrium officinale (L.) Scop (the "singers'plant”) is the most popular herbal remedy for voice care, but many other plants are employed in phytopreparations. The mechanisms of action of these botanicals include anti-bacterial, anti-inflammatory, mucolytic, antinociceptive and other general activities; nevertheless, mechanisms that could be specifically referred to voice are often unknown. We collected information on plants used worldwide for voice care; the plants have been organized in a database (Herbs for Voice Database) and classified according to the bioactive compounds, their molecular targets and the pathologies they are recommended for. The data were analyzed with the aim to identify some possible common mechanism of action and the molecular targets involved. The analysis of data shows that an important pathway involves the somatosensory TRPA1 (Transient Receptor Potential Ankyrin type 1) ion channel, a well-known mediator of irritation, inflammatory and neurogenic pain. Agonists of this ion channel have been identified in 27 over 44 plants, corresponding to 61,3% of the plants in the database. Also TRPM8 (Transient Receptor Potential Melastatin type 8), involved in the perception of coolness, was identified among the molecular targets. This finding reinforces the hypothesis that these somatosensory ion channels could be involved in relevant mechanisms of action of these traditional remedies and open new perspectives in the rational study of voice phytopharmacology and therapy. This research was funded by FONDAZIONE CARIPLO (Milano, I), University of Milano (I) and Conservatorio di Musica G. Verdi (Milano, I), grant number 2017-1653.