Studies of the Toxicological Potential of Capsinoids, XII: Pharmacokinetic Study of Capsinoid-Containing CH-19 Sweet Extract in Rats

Abstract

Pharmacokinetics of the main capsinoid components of CH-19 Sweet extract (capsiate, dihydrocapsiate, and nordihydrocapsiate) were investigated in rats receiving a single gavage dose of extract containing 10 or 100 mg of capsinoids per kilogram in medium-chain triglyceride. Resultant blood levels of these capsinoids and a capsinoid metabolite, vanillyl alcohol, were measured in portal vein and systemic blood. Capsinoids were never detected. Portal compartment vanillyl alcohol concentrations and area under the plasma concentration versus time curve increased approximately with dose, whereas the time to maximum concentration of vanillyl alcohol was independent of dose (30 minutes post dosing), suggesting that precipitation in the stomach or intestines was unlikely. Vanillyl alcohol levels were just barely detectable in systemic plasma (5 minutes post dosing). Significant levels of vanillyl alcohol conjugates, sulfate, and glucuronide were detected in the systemic blood. Given that the orally administered capsinoids were never detected in the portal vein or systemic circulation, these compounds must be broken down (chemically or enzymatically) to vanillyl alcohol.

Studies of the Toxicological Potential of Capsinoids, XI: Pharmacokinetic and Tissue Distribution Study of 14C-Dihydrocapsiate and Metabolites in Rats

“…This finding is consistent with those of Shirai et al, 20 who reported that levels of DHC were not detected in the portal vein after single oral administration of capsinoids (a mixture of capsiate, DHC, and nordihydrocapsiate) to rats. These results suggest that DHC is rapidly and apparently completely metabolized in the rat.…”

Capsaicin reduces the metastatic burden in the transgenic adenocarcinoma of the mouse prostate model

“…There are only a few studies that have examined the pharmokinetics and bioavailability capsaicin, most of which have been carried out in rats . In humans, capsaicin is generally assessed through the consumption of chilli peppers and related spices : One study have reported serum concentrations of 8.1 nM after oral consumption of 5 g of chilli peppers, whereas other studies have reported a concentrations ranging from 13.4–16.3 ng/ml after the consumption of chilli‐containing meal .…”

“…Future studies examining how capsaicin may be altering these enzymes may be of relevance for developing therapeutic strategies for preventing the progression of neuroendocrine and castrate-resistant tumors [30]. There are only a few studies that have examined the pharmokinetics and bioavailability capsaicin, most of which have been carried out in rats [31][32][33]. In humans, capsaicin is generally assessed through the consumption of chilli peppers and related spices [34]: One study have reported serum concentrations of 8.1 nM after oral consumption of 5 g of chilli peppers, whereas other studies have reported a concentrations ranging from 13.4-16.3 ng/ml after the consumption of chilli-containing meal [35,36].…”

Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses

“…Capsiate is an equipotent capsaicin analog that was identified in a much less pungent chili pepper cultivar, CH-19 sweet (22), and has an ester bond in its structure in place of the amide bond in capsaicin, making it highly vulnerable in the digestive system. Use of this TRP channel ligand, therefore, enables us to evaluate the effect of selective stimulation of TRP channels in the GI tract without affecting those in other sensory systems (5,6,54). Here, we show that selective activation of TRP channels, presumably the TRPV1 type, located in the upper GI tract is sufficient to trigger the thermogenic reflex through the intermediary step of activating vagal afferents and sympathetic efferents innervating the BAT.…”

“…Capsiate used in this study was synthesized from side-chain fatty acid substances in capsaicinoids extracted from chili pepper (28) and therefore was composed of capsiate (53.6%), dihydrocapsiate (27.5%), and nordihydrocapsiate (4.6%) (30). Dihydrocapsiate and nordihydrocapsiate are almost equally vulnerable in aqueous conditions as well as in the digestive tract, with a similar bioavailability by oral ingestion (5,54) and with a similar potency to TRPV1 channels to pure capsiate (52). C6 (Sigma) was stored as a stock solution and diluted immediately before the experiment.…”