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Perilla Derived Compounds Mediate Human TRPA1 Channel Activity

Alberto Maria Cattaneo, Yuriy V Bobkov, Elizabeth A Corey, Gigliola Borgonovo and Angela Bassoli

Compounds from food plants affecting the somatosensory system, like Perilla frutescens (L.), are well known for their flavoring, pharmacological and medical properties. Yet the exact mechanisms underlying their activity are still poorly understood. Transient Receptor Potential (TRP) channels involved in chemestetic sensations likely represent some of the primary targets for these compounds. Using a heterologous expression system and calcium imaging we show that a number of Perilla derived compounds (S-(-)-1,8-p-menthadiene-7-al (perillaldehyde, PA); 3-(4-methyl- 1-oxopentyl)furan (perillaketone, PK); 1,2,4-trimethoxy-5-[(E)-prop-1-enyl]benzene (α-asarone, ASA)) and synthetic compounds derivative from Perilla (3-(4-methoxy-phenyl)-1-furan-2-yl-propenone (PK-16) and 3-(4-chloro-phenyl)- 1-furan-2-yl-propenone (PK-18)) are capable of activating the human TRP Ankyrin family channel (h-TRPA1). The compounds tested appear to be partial agonists of the channel with the potency sequence (EC50, μM): PK- 16(107.7)>PA (160.5)>ASA(210.9)>PK(350). Our findings provide important insight into the functional properties of the compounds derived from P. frutescens and reveal new perspectives for the design of tools for pharmaceutical, agricultural and food industry applications.