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 Ca(2+) 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.

Juglone in Oxidative Stress and Cell Signaling

“…Another interesting effect of juglone is its ability to activate the Ca 2+ channel activity of transient receptor potential ankyrin subtype 1 channel, TRPA1 [128]. TRPA1 is an irritant sensor and plays a key role in nociception, irritant sensing and mechanical sensation [129].…”

“…Thus, the hydroxyl group at the 5 position likely plays a mechanistic role in this activity. Further, since neither extracellular nor intracellular application of catalase (a hydrogen peroxide scavenger) prevented the activation [128], it is not likely that redox cycling-mediated ROS production is involved in this mechanism.…”

Synthesis of Phenylpropanoids via Matsuda–Heck Coupling of Arene Diazonium Salts

“…After cooling to ambient temperature, the reaction mixture was filtered through a pad of Celite, which was washed with ethanol. The filtrate was evaporated and the residue was purified by column chromatography on silica, using hexane/MTBE mixtures as eluent, to furnish 15 (87%, 67 mg, 0.32 mmol): brownish oil; 1 H NMR (300 MHz, CDCl 3 ) δ 6.71 (d, J = 8.4 Hz, 1H), 6.28 (d, J = 2.6 Hz, 1H), 6.18 (dd, J = 8.4, 2.6 Hz, 1H), 5.49 (tm, J = 6.8 Hz, 1H), 4.46 (d, J = 6.7 Hz, 2H), 3.79 (s, 3H), 1.74 (s, 3H), 1.68 (s, 3H); 13 Ferulic Acid Methyl Ester (17). 62 To a solution of 16 (76.5 mg, 0.25 mmol) and Pd(OAc) 2 (2.8 mg, 5 mol%) in methanol (2.5 mL) was added methyl acrylate (45 μL, 0.50 mmol) at ambient temperature and the reaction mixture was stirred until the gas evolution had ceased.…”

A New Phytochemical and Anti-oxidant and Anti-inflammatory Activities of Different Lactuca sativa L. var. crispa Extracts

“…Chemistry: GOFA 1 (Figure 1) was chemically synthesized as already reported and its purity (> 98 %) assessed by GC/MS and 1 H NMR [12]. .39 min.…”