Discovery and isolation of novel capsaicinoids and their TRPV1-related activity
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
40320114
DOI
10.1016/j.ejphar.2025.177700
PII: S0014-2999(25)00454-6
Knihovny.cz E-zdroje
- Klíčová slova
- Calcium imaging, Capsaicin, MS/MS spectrometry, Metabolomics, Natural products, TRPV1, Vanilloids,
- MeSH
- Capsicum * chemie MeSH
- HEK293 buňky MeSH
- kapsaicin * farmakologie izolace a purifikace chemie analogy a deriváty MeSH
- kationtové kanály TRPV * metabolismus MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- metabolomika MeSH
- objevování léků * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kapsaicin * MeSH
- kationtové kanály TRPV * MeSH
- Trpv1 protein, rat MeSH Prohlížeč
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.
Broad Institute Boston USA; GIGA Institute University of Liège Liège Belgium
CZ OPENSCREEN Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czechia
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Prague Czechia
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