Discovery and isolation of novel capsaicinoids and their TRPV1-related activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00635650" target="_blank" >RIV/61388963:_____/25:00635650 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/25:00635650 RIV/00216208:11110/25:10498553

Výsledek na webu

<a href="https://doi.org/10.1016/j.ejphar.2025.177700" target="_blank" >https://doi.org/10.1016/j.ejphar.2025.177700</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejphar.2025.177700" target="_blank" >10.1016/j.ejphar.2025.177700</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Discovery and isolation of novel capsaicinoids and their TRPV1-related activity

Popis výsledku v původním jazyce

Chilis contain capsaicin and other structurally related molecules known as capsaicinoids. Capsaicin's target protein, the transient receptor potential cation channel subfamily V member 1 (TRPV1), has been linked to many post-activation effects, including changes in metabolism and pain sensation. Capsaicinoids also bind to TRPV1, but current studies often disregard non-capsaicin interactions. To fill in these gaps, we screened 40 different chili varieties derived from four Capsicum species by means of untargeted metabolomics and a rat TRPV1 (rTRPV1) calcium influx activation assay. The resulting capsaicinoid profiles were specific to each variety but only partially corresponded with species delimitations. Based on rTRPV1 activation elicited by crude chili extracts, capsaicinoids act in an additive manner and a capsaicinoid profile can serve as a gauge of this activation. In addition, we isolated eighteen capsaicinoids, including five previously unreported ones, and confirmed their structure by NMR and MS/MS. We then tested rTRPV1 activation by 23 capsaicinoids and three related compounds. This testing revealed that even slight deviations from the structure of capsaicin reduce the ability to activate the target, with a mere single hydroxylation on the acyl tail reducing potency towards rTRPV1 by more than 100-fold. In addition, we tested how rTRPV1 activity changes in the presence of capsaicin together with non-activating capsaicin analogs and weakly activating capsaicinoids and found both classes of molecules to positively modulate the effects of capsaicin. This demonstrates that even such compounds have measurable pharmacological effects, making a case for the use and study of natural chili extracts.

Název v anglickém jazyce

Discovery and isolation of novel capsaicinoids and their TRPV1-related activity

Popis výsledku anglicky

Chilis contain capsaicin and other structurally related molecules known as capsaicinoids. Capsaicin's target protein, the transient receptor potential cation channel subfamily V member 1 (TRPV1), has been linked to many post-activation effects, including changes in metabolism and pain sensation. Capsaicinoids also bind to TRPV1, but current studies often disregard non-capsaicin interactions. To fill in these gaps, we screened 40 different chili varieties derived from four Capsicum species by means of untargeted metabolomics and a rat TRPV1 (rTRPV1) calcium influx activation assay. The resulting capsaicinoid profiles were specific to each variety but only partially corresponded with species delimitations. Based on rTRPV1 activation elicited by crude chili extracts, capsaicinoids act in an additive manner and a capsaicinoid profile can serve as a gauge of this activation. In addition, we isolated eighteen capsaicinoids, including five previously unreported ones, and confirmed their structure by NMR and MS/MS. We then tested rTRPV1 activation by 23 capsaicinoids and three related compounds. This testing revealed that even slight deviations from the structure of capsaicin reduce the ability to activate the target, with a mere single hydroxylation on the acyl tail reducing potency towards rTRPV1 by more than 100-fold. In addition, we tested how rTRPV1 activity changes in the presence of capsaicin together with non-activating capsaicin analogs and weakly activating capsaicinoids and found both classes of molecules to positively modulate the effects of capsaicin. This demonstrates that even such compounds have measurable pharmacological effects, making a case for the use and study of natural chili extracts.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GM21-11563M" target="_blank" >GM21-11563M: Mapování chemodiverzity pepřovníkovitých rostlin pomocí nové generace platformy MZmine</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Pharmacology

ISSN

0014-2999

e-ISSN

1879-0712

Svazek periodika

999

Číslo periodika v rámci svazku

July

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

13

Strana od-do

177700

Kód UT WoS článku

001491160100002

EID výsledku v databázi Scopus

2-s2.0-105004602485