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This preclinical study examined the role of herbal Amara extract (containing <jats:italic>Artemisia absinthium<\/jats:italic>, <jats:italic>Centaurium erythraea<\/jats:italic>, <jats:italic>Cichorium intybus<\/jats:italic>, <jats:italic>Gentiana lutea<\/jats:italic>, <jats:italic>Juniperus communis<\/jats:italic>, <jats:italic>Achillea millefolium<\/jats:italic>, <jats:italic>Peucedanum ostruthium<\/jats:italic>, <jats:italic>Salvia officinalis<\/jats:italic>, and <jats:italic>Taraxacum<\/jats:italic> extracts) on gastric (fundus) accommodation and the possible implication of muscarinic receptors in its regulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effect of Amara extract on fundus motility was investigated in organ baths of smooth muscle strips isolated from the fundus of guinea pigs, and the role of the muscarinic receptor pathway was evaluated using functional and radioligand binding assays in cell lines expressing the M2 or M3 muscarinic receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Amara extract inhibited carbachol\u2010induced contraction of guinea pig smooth muscle strips in a dose\u2010dependent manner. This relaxant effect was not affected by the M3 antagonist J\u2010104129. Amara extract also inhibited M2, but not M3, receptor activity in CHO\u2010K1 cells (IC<jats:sub>50<\/jats:sub> 219\u2009\u03bcg\u2009mL<jats:sup>\u22121<\/jats:sup>), and specifically bound the M2 receptor (IC<jats:sub>50<\/jats:sub> 294\u2009\u03bcg\u2009mL<jats:sup>\u22121<\/jats:sup>). Of the nine herbal components of Amara extract, <jats:italic>Juniperus communis<\/jats:italic>, <jats:italic>P. ostruthium<\/jats:italic>, and <jats:italic>Salvia officinalis<\/jats:italic> inhibited M2 receptor activity (IC<jats:sub>50<\/jats:sub> 32.0, 20.8, and 20.1\u2009\u03bcg\u2009mL<jats:sup>\u22121<\/jats:sup>, respectively), and <jats:italic>P. ostruthium<\/jats:italic> was sufficient to reverse carbachol\u2010induced ex\u00a0vivo contraction of guinea pig fundic smooth muscles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Inferences<\/jats:title><jats:p>Amara extract relaxes gastric smooth muscles by inhibiting the M2 muscarinic receptor. This study suggests the potential benefit of Amara extract for patients with impaired gastric accommodation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14924","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T10:50:08Z","timestamp":1727693408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Herbal Amara extract induces gastric fundus relaxation via inhibition of the <scp>M2<\/scp> muscarinic receptor"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6340-2031","authenticated-orcid":false,"given":"Maria\u2010Riera","family":"Piqu\u00e9\u2010Borr\u00e0s","sequence":"first","affiliation":[{"name":"Preclinical Research and Development Weleda AG  Arlesheim Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann","family":"R\u00f6hrl","sequence":"additional","affiliation":[{"name":"Preclinical Research and Development Weleda AG  Arlesheim Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald","family":"K\u00fcnstle","sequence":"additional","affiliation":[{"name":"Preclinical Research and Development Weleda AG  Arlesheim Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2011.05.005"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2018.02.059"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2021.113951"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2017.02.037"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2010.09.030"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2019.02.017"},{"key":"e_1_2_11_8_1","unstructured":"WeledaAG.AMARA\u2010TROPFEN. 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