{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:11:01Z","timestamp":1788844261164,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development and Innovation Fund of Hungary","award":["TKP2021-EGA-13"],"award-info":[{"award-number":["TKP2021-EGA-13"]}]},{"name":"National Research, Development and Innovation Fund of Hungary","award":["TKP2021-EGA-16"],"award-info":[{"award-number":["TKP2021-EGA-16"]}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"crossref","award":["BO\/00102\/25"],"award-info":[{"award-number":["BO\/00102\/25"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"crossref","award":["BO\/00189\/24\/5"],"award-info":[{"award-number":["BO\/00189\/24\/5"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"crossref"}]},{"award":["BO\/00102\/25"],"award-info":[{"award-number":["BO\/00102\/25"]}],"id":[{"id":"https:\/\/ror.org\/02ks8qq67","id-type":"ROR","asserted-by":"publisher"}]},{"award":["BO\/00189\/24\/5"],"award-info":[{"award-number":["BO\/00189\/24\/5"]}],"id":[{"id":"https:\/\/ror.org\/02ks8qq67","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Research, Development and Innovation Office","award":["RRF-2.3.1-21-2022-00015"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00015"]}]},{"award":["RRF-2.3.1-21-2022-00015"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00015"]}],"id":[{"id":"https:\/\/ror.org\/03g2am276","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are key nociceptive ion channels involved in chemosensation, pain signaling, and neurogenic inflammation. Several sesquiterpene lactones target TRPA1, but the activity profile of these secondary metabolites of the common ragweed (Ambrosia artemisiifolia) remains uncharacterized. Purpose: The purpose of this study was to explore the activity of five ragweed sesquiterpene lactones on TRPA1 and TRPV1, respectively. Methods: We investigated the effects of five ragweed-derived sesquiterpene lactones\u2014acetoxydihydrodamsin, costunolide, isoalantolactone, peruvin, and psilostachyin\u2014on TRPA1 and TRPV1 using 45Ca2+ uptake in receptor-overexpressing CHO cells and covalent docking to human TRPA1. Results: Costunolide, isoalantolactone and acetoxydihydrodamsin induced TRPA1 activation (counts per minute of 45Ca2+ uptake at 40 \u00b5M concentration: 5070 \u00b1 346.5, 10,197 \u00b1 1237, 3704 \u00b1 1634, respectively) but not TRPV1 activation, as demonstrated by Ca2+ influx. Acetoxydihydrodamsin induced concentration-dependent TRPA1 activation that was significantly inhibited by 10 \u00b5M of the selective antagonist HC-030031. Docking studies demonstrated covalent interactions of costunolide, isoalantolactone, and acetoxydihydrodamsin (\u221247.3, \u221251.5, and \u221245.0 kcal\/mol FITTED score) with the electrophile-sensitive binding region of TRPA1. Conclusions: Ragweed sesquiterpene lactones act as TRPA1 agonists without detectable TRPV1 activation. This study provides the first data identifying acetoxydihydrodamsin as a TRPA1 agonist, expanding the pharmacological map of ragweed sesquiterpene lactones. These results suggest that these metabolites may contribute to both the irritant properties and the pharmacological potentials of A. artemisiifolia.<\/jats:p>","DOI":"10.3390\/ph19091404","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:07:06Z","timestamp":1788768426000},"page":"1404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sesquiterpene Lactone Derivatives of Ambrosia artemisiifolia Act as Agonists of the Transient Receptor Potential Ankyrin 1 Ion Channel"],"prefix":"10.3390","volume":"19","author":[{"given":"Bal\u00e1zs Zolt\u00e1n","family":"Zsid\u00f3","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, Szigeti u. 12, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8013-971X","authenticated-orcid":false,"given":"Csaba","family":"Het\u00e9nyi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, Szigeti u. 12, H-7624 P\u00e9cs, Hungary"},{"name":"National Laboratory for Drug Research and Development, Magyar Tud\u00f3sok krt. 2, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Bal\u00e1zs","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Institute of Pharmacognosy, University of Szeged, E\u00f6tv\u00f6s u. 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4088-3333","authenticated-orcid":false,"given":"Dezs\u0151","family":"Csupor","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Institute of Pharmacognosy, University of Szeged, E\u00f6tv\u00f6s u. 6, H-6720 Szeged, Hungary"},{"name":"Faculty of Pharmacy, Institute of Clinical Pharmacy, University of Szeged, Szikra u. 8, H-6720 Szeged, Hungary"},{"name":"Institute of Translational Medicine, Medical School, University of P\u00e9cs, Szigeti u. 12, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3538-377X","authenticated-orcid":false,"given":"Tivadar","family":"Kiss","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Institute of Pharmacognosy, University of Szeged, E\u00f6tv\u00f6s u. 6, H-6720 Szeged, Hungary"},{"name":"HUN-REN SZTE Biologically Active Natural Products Research Group, E\u00f6tv\u00f6s u. 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Bogl\u00e1rka","family":"Csupor-L\u00f6ffler","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, University of P\u00e9cs, R\u00f3kus u. 2, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, Szigeti u. 12, H-7624 P\u00e9cs, Hungary"},{"name":"National Laboratory for Drug Research and Development, Magyar Tud\u00f3sok krt. 2, H-1117 Budapest, Hungary"},{"name":"HUN-REN PTE Chronic Pain Research Group, Szigeti \u00fat 12, H-7624 P\u00e9cs, Hungary"},{"name":"PharmInVivo Ltd., Szondi u. 10, H-7629 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"\u00c9va","family":"Sz\u0151ke","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, Szigeti u. 12, H-7624 P\u00e9cs, Hungary"},{"name":"National Laboratory for Drug Research and Development, Magyar Tud\u00f3sok krt. 2, H-1117 Budapest, Hungary"},{"name":"HUN-REN PTE Chronic Pain Research Group, Szigeti \u00fat 12, H-7624 P\u00e9cs, 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