curcumin and resiniferatoxin

Vanilloids are natural molecules identified in a plethora of foods normally ingested through the diet. They mediate apoptosis through a direct pathway (independent of TRPV-1, the receptor for vanilloids) and through an indirect pathway, i.e., thanks to the interaction with TRPV-1 and the successive intracellular calcium growth [Ca2+]i. Some vanilloids, such as capsaicin, dihydrocapsaicin and resiniferatoxin (the ultrapotent analogue of capsaicin, extractable from Euphorbia resinifera), may be considered as coenzyme Qantagonists: in fact, they inhibit the run of the electrons through the electron transport chain, so determining an excess of reactive oxygen species (ROS). A second effect of the interaction between the vanilloids and TRPV-1 receptor may be reported: it is the fast decrease of the transmembrane mitochondrial potential (delta psi m). Through the direct pathway, on the contrary, the vanilloids induce apoptosis also interacting with caspases, particularly caspase 1 and 3. On the whole, the vanilloids are able to lead to the intracellular calcium growth and consequently to the evidence of precocious and late elements of apoptosis.

Topics: Apoptosis; Calcium Signaling; Capsaicin; Caspases; Curcumin; Diterpenes; Enzyme Inhibitors; Humans; Male; Prostatic Neoplasms; TRPV Cation Channels

Although capsaicin not only activates transient receptor potential vanilloid-1 (TRPV1) channels but also inhibits nerve conduction, the latter action has not yet been fully examined. The purpose of the present study was to know whether various vanilloids have an inhibitory action similar to that of capsaicin and further to compare their actions with that of local anesthetic procaine.. Fast-conducting compound action potentials (CAPs) were recorded from frog sciatic nerve fibers by using the air-gap method.. Capsaicin reversibly and concentration-dependently reduced the peak amplitude of the CAP. TRPV1 antagonist capsazepine did not affect the capsaicin activity, and powerful TRPV1 agonist resiniferatoxin had no effect on CAPs, indicating no involvement of TRPV1 channels. Capsaicin analogs and other various vanilloids also inhibited CAPs in a concentration-dependent manner. An efficacy sequence of these inhibitions was capsaicin=dihydrocapsaicin>capsiate>eugenol>guaiacol≥zingerone≥vanillin>vanillylamine. Vanillic acid had almost no effect on CAPs; olvanil and curcumin appeared to be effective less than capsaicin. Capsaicin and eugenol were, respectively, ten- and two-fold effective more than procaine in CAP inhibition, while each of guaiacol, zingerone and vanillin was five-fold effective less than procaine.. Various vanilloids exhibit CAP inhibition, the extent of which is determined by the property of the side chain bound to the vanillyl group, and some of them are more effective than procaine. These results may serve to unveil molecular mechanisms for capsaicin-induced conduction block and to develop antinociceptive drugs related to capsaicin.

Topics: Action Potentials; Animals; Antipruritics; Benzaldehydes; Benzylamines; Capsaicin; Curcumin; Diterpenes; Eugenol; Female; Guaiacol; Male; Procaine; Ranidae; Sciatic Nerve; Structure-Activity Relationship; TRPV Cation Channels; Vanillic Acid