{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T19:21:05Z","timestamp":1770492065954,"version":"3.49.0"},"reference-count":62,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,20]],"date-time":"2022-11-20T00:00:00Z","timestamp":1668902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010067","name":"Government of Aragon","doi-asserted-by":"publisher","award":["B44_20D-Phyto-Pharm: Principios vegetales bioactivos y ciencias farmac\u00e9uticas"],"award-info":[{"award-number":["B44_20D-Phyto-Pharm: Principios vegetales bioactivos y ciencias farmac\u00e9uticas"]}],"id":[{"id":"10.13039\/501100010067","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010067","name":"Government of Aragon","doi-asserted-by":"publisher","award":["JIUZ-2018-BIO-09"],"award-info":[{"award-number":["JIUZ-2018-BIO-09"]}],"id":[{"id":"10.13039\/501100010067","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010067","name":"Government of Aragon","doi-asserted-by":"publisher","award":["JIUZ-2021-BIO-08"],"award-info":[{"award-number":["JIUZ-2021-BIO-08"]}],"id":[{"id":"10.13039\/501100010067","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010067","name":"Government of Aragon","doi-asserted-by":"publisher","award":["2122041"],"award-info":[{"award-number":["2122041"]}],"id":[{"id":"10.13039\/501100010067","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universidad de Zaragoza","award":["B44_20D-Phyto-Pharm: Principios vegetales bioactivos y ciencias farmac\u00e9uticas"],"award-info":[{"award-number":["B44_20D-Phyto-Pharm: Principios vegetales bioactivos y ciencias farmac\u00e9uticas"]}]},{"name":"Universidad de Zaragoza","award":["JIUZ-2018-BIO-09"],"award-info":[{"award-number":["JIUZ-2018-BIO-09"]}]},{"name":"Universidad de Zaragoza","award":["JIUZ-2021-BIO-08"],"award-info":[{"award-number":["JIUZ-2021-BIO-08"]}]},{"name":"Universidad de Zaragoza","award":["2122041"],"award-info":[{"award-number":["2122041"]}]},{"name":"Universidad San Jorge","award":["B44_20D-Phyto-Pharm: Principios vegetales bioactivos y ciencias farmac\u00e9uticas"],"award-info":[{"award-number":["B44_20D-Phyto-Pharm: Principios vegetales bioactivos y ciencias farmac\u00e9uticas"]}]},{"name":"Universidad San Jorge","award":["JIUZ-2018-BIO-09"],"award-info":[{"award-number":["JIUZ-2018-BIO-09"]}]},{"name":"Universidad San Jorge","award":["JIUZ-2021-BIO-08"],"award-info":[{"award-number":["JIUZ-2021-BIO-08"]}]},{"name":"Universidad San Jorge","award":["2122041"],"award-info":[{"award-number":["2122041"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Functional gastrointestinal diseases (FGID) are worldwide prevalent conditions. Pharmacological treatments can be ineffective, leading the population to turn to herbal or traditional remedies. Helichrysum stoechas (L.) Moench is a medicinal plant traditionally used in the Iberian Peninsula to treat digestive disorders, but its effects on gastrointestinal motility have not been scientifically demonstrated. The aim of this work was to evaluate the antispasmodic effect of a polyphenolic extract of H. stoechas (HSM), its mechanism of action and its antioxidant activity. Isometric myography studies were performed in rat ileum, and malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) levels were measured in rat jejunum. HSM reduced the integrated mechanical activity of spontaneous contractions. In Ca2+-free medium, HSM reduced the concentration\u2013response curve of CaCl2 similarly to verapamil. Pre-incubation with the extract blocked the contraction induced by Bay K8644, KCl and carbachol. L-NAME, ODQ, Rp-8-Br-PET-cGMPS, KT-5823, apamin, TRAM-34 and charybdotoxin reduced the relaxant effect of the extract on spontaneous contractions. MDA+4-HDA levels in LPS-treated tissue were reduced by the extract, showing antioxidant activity. In conclusion, HSM showed antispasmodic activity through inhibition of Ca2+ influx, activation of the NO\/PKG\/cGMP pathway and opening of Ca2+-activated K+ channels. The results suggest that H. stoechas could help in the prevention or treatment of FGIDs.<\/jats:p>","DOI":"10.3390\/ijms232214422","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T03:05:11Z","timestamp":1668999911000},"page":"14422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Involvement of NO\/cGMP Signaling Pathway, Ca2+ and K+ Channels on Spasmolytic Effect of Everlasting Flower Polyphenolic Extract (Helichrysum stoechas (L.) Moench)"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2231-7565","authenticated-orcid":false,"given":"Marta Sof\u00eda","family":"Valero","sequence":"first","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Fisiolog\u00eda y Medicina Legal y Forense, Universidad de Zaragoza, 50009 Zaragoza, Spain"},{"name":"Instituto Agroalimentario de Arag\u00f3n, IA2, Universidad de Zaragoza-CITA, 50830 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6969-1055","authenticated-orcid":false,"given":"V\u00edctor","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Instituto Agroalimentario de Arag\u00f3n, IA2, Universidad de Zaragoza-CITA, 50830 Zaragoza, Spain"},{"name":"Facultad de Ciencias de la Salud, Universidad San Jorge, Villanueva de G\u00e1llego, 50830 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8584-3979","authenticated-orcid":false,"given":"Marta","family":"Castro","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Fisiolog\u00eda y Medicina Legal y Forense, Universidad de Zaragoza, 50009 Zaragoza, Spain"},{"name":"Instituto Agroalimentario de Arag\u00f3n, IA2, Universidad de Zaragoza-CITA, 50830 Zaragoza, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IIS Arag\u00f3n), 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3982-2282","authenticated-orcid":false,"given":"Carlota","family":"G\u00f3mez-Rinc\u00f3n","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Universidad San Jorge, Villanueva de G\u00e1llego, 50830 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2114-0577","authenticated-orcid":false,"given":"Mar\u00eda Pilar","family":"Arruebo","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Fisiolog\u00eda y Medicina Legal y Forense, Universidad de Zaragoza, 50009 Zaragoza, Spain"},{"name":"Instituto Agroalimentario de Arag\u00f3n, IA2, Universidad de Zaragoza-CITA, 50830 Zaragoza, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IIS Arag\u00f3n), 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7972-7119","authenticated-orcid":false,"given":"Francisco","family":"Les","sequence":"additional","affiliation":[{"name":"Instituto Agroalimentario de Arag\u00f3n, IA2, Universidad de Zaragoza-CITA, 50830 Zaragoza, Spain"},{"name":"Facultad de Ciencias de la Salud, Universidad San Jorge, Villanueva de G\u00e1llego, 50830 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7412-2073","authenticated-orcid":false,"given":"Miguel \u00c1ngel","family":"Plaza","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Fisiolog\u00eda y Medicina Legal y Forense, Universidad de Zaragoza, 50009 Zaragoza, Spain"},{"name":"Instituto Agroalimentario de Arag\u00f3n, IA2, Universidad de Zaragoza-CITA, 50830 Zaragoza, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Arag\u00f3n (IIS Arag\u00f3n), 50009 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1016\/S0140-6736(20)32115-2","article-title":"Functional gastrointestinal disorders: Advances in understanding and management","volume":"396","author":"Black","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1159\/000504570","article-title":"Use of Evidence-Based Herbal Medicines for Patients with Functional Gastrointestinal Disorders: A Conceptional Framework for Risk-Benefit Assessment and Regulatory Approaches","volume":"38","author":"Holtmann","year":"2020","journal-title":"Dig. 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