Journal club 2016. 03. 11.

Plumbagin, Juglone, and Boropinal as Novel TRPA1 Agonists
Kerstin Hill,*,† Serena Fiorito,‡ Vito Alessandro Taddeo,‡ Anja Schulze,§ Marion Leonhardt,† Francesco Epifano,*,‡ and Salvatore Genovese‡
†Rudolf-Boehm-InstitutfürPharmakologieundToxikologie,UniversitaẗLeipzig,Har̈telstr.16-18,04107Leipzig,Germany ‡Department of Pharmacy, University “G. D’Annunzio” of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy §Fraunhofer-Institut für Zelltherapie und Immunologie IZI, Biozentrum, Weinbergweg 22, 06120 Halle, Germany

Plumbagin, Juglone, and Boropinal as Novel TRPA1 Agonists

ABSTRACT: A series of seven oxyprenylated phenylpropanoids and naphthoquinones were tested regarding their ability to activate transient receptor potential ankyrin subtype 1 channel (TRPA1). Three of the assayed compounds, namely, boropinal (3), juglone (5), and plumbagin (7), acted as strong modulators of TRPA1 channels with EC50 values of 9.8, 1.7,and 0.5 μM, respectively, as assessed by Ca2+ assays. Moreover, the compounds elicited TRPA1 currents in electrophysiological whole cell recordings. We additionally provide evidence that plumbagin activated TRPA1-positive neurons isolated from mouse dorsal root ganglion neurons but did not affect sensory neurons from TRPA1-deficient mice. The high potencies of plumbagin and juglone to activate TRPA1 channels may explain the molecular basis of the mucosal irritant properties of these compounds as well as of related naphthoquinones and phytopreparations, as widely reported in the literature.