Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1)

Abstract

1 We have characterised the effects of piperine, a pungent alkaloid found in black pepper, on the human vanilloid receptor TRPV1 using whole-cell patch-clamp electrophysiology. 2 Piperine produced a clear agonist activity at the human TRPV1 receptor yielding rapidly activating whole-cell currents that were antagonised by the competitive TRPV1 antagonist capsazepine and the non-competitive TRPV1 blocker ruthenium red. 3 The current-voltage relationship of piperine-activated currents showed pronounced outward rectification (2574-fold between À70 and þ 70 mV) and a reversal potential of 0.070.4 mV, which was indistinguishable from that of the prototypical TRPV1 agonist capsaicin. 4 Although piperine was a less potent agonist (EC 50 ¼ 37.971.9 mM) than capsaicin (EC 50 ¼ 0.2970.05 mM), it demonstrated a much greater efficacy (approximately two-fold) at TRPV1. 5 This difference in efficacy did not appear to be related to the proton-mediated regulation of the receptor since a similar degree of potentiation was observed for responses evoked by piperine (230720%, n ¼ 11) or capsaicin (284732%, n ¼ 8) upon acidification to pH 6.5. 6 The effects of piperine upon receptor desensitisation were also unable to explain this effect since piperine resulted in more pronounced macroscopic desensitisation (t 1/2 ¼ 9.970.7 s) than capsaicin (t 1/2 420 s) and also caused greater tachyphylaxis in response to repetitive agonist applications. 7 Overall, our data suggest that the effects of piperine at human TRPV1 are similar to those of capsaicin except for its propensity to induce greater receptor desensitisation and, rather remarkably, exhibit a greater efficacy than capsaicin itself. These results may provide insight into the TRPV1-mediated effects of piperine on gastrointestinal function.

6-Shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson's disease models via anti-neuroinflammation

“…The present study demonstrated that 6-shogaol, a pungent compound isolated from ginger, protects dopaminergic neurons against MPP + -and MPTP-induced neurotoxicity by inhibiting inflammatory pathways. Natural pungent compounds from plants have been suggested to play a role in protection via antioxidant, anti-inflammatory, and anti-carcinogenic activities [28,29] . For example, various experimental and clinical studies have shown that capsaicin and piperine isolated from pepper fruits, paradol isolated from Amomum melegueta Roscoe, and allicin isolated from garlic exhibit the most potent neuroprotective and anti-inflammatory effects identified for plant compounds to date [28,30,31] .…”

Trigeminal Chemesthesis

“…Nevertheless, the ion-channels responding to the last two chemicals are also thermoreceptors that respond to warm/hot and cool/cold temperatures, respectively. In fact, the capsaicin channel not only responds to chemically-related vanilloids (Szallasi and Blumberg, 1999), but also to unrelated VOCs (Silver et al, 2006;Trevisani et al, 2002), to other pungent compounds (Macpherson et al, 2005;McNamara et al, 2005) and even to inorganic volatiles (Trevisani et al, 2005).…”

LASSBio‐881: an N‐acylhydrazone transient receptor potential vanilloid subfamily type 1 antagonist orally effective against the hypernociception induced by capsaicin or partial sciatic ligation

“…However, anandamide can also stimulate TRPV1 (Zygmunt et al, 1999), and ligands of cannabinoid receptors are thought to have the potential to be ligands of the TRPV1 channel as well (Di Marzo et al, 2007). As LASSBio-881 has a 1,3-benzodioxolyl moiety derived from safrole that is present in pungent TRPV1 agonists like piperine (McNamara et al, 2005), we sought to investigate whether this compound affects TRPV1 function.…”