{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T10:50:03Z","timestamp":1772621403227,"version":"3.50.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009392","name":"Prince Sattam bin Abdulaziz University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019725","name":"Deanship of Scientific Research, Prince Sattam bin Abdulaziz University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The leaves of\n                      <jats:italic>Otostegia fruticosa<\/jats:italic>\n                      have been used in traditional medical systems to treat diarrhea and gut spasms. In this study, we evaluate the possible gut inhibitory roles of the crude extract of\n                      <jats:italic>O. fruticosa<\/jats:italic>\n                      using mice for\n                      <jats:italic>in vivo<\/jats:italic>\n                      , rabbits for\n                      <jats:italic>ex vivo<\/jats:italic>\n                      , and selected enteric pathogenic bacteria for\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Castor-oil-induced diarrhea was used to assess the diarrheal protection of the extract in mice, while CaCl\n                      <jats:sub>2<\/jats:sub>\n                      -induced excitatory concentration\u2013response curves (CRCs) and isoprenaline-induced inhibitory CRCs were constructed for isolated rabbit intestines to explore Ca\n                      <jats:sup>++<\/jats:sup>\n                      channel blockade and phosphodiesterase (PDE) inhibitory-like pathways, respectively. Moreover, the antibacterial activity of the extract was tested against selected bacteria.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The extract protected mice from castor-oil-mediated diarrhea significantly compared to the saline control group at doses of 200 and 400\u00a0mg\/kg. In the isolated jejunum, the extract inhibited both spontaneous and high K\n                      <jats:sup>+<\/jats:sup>\n                      -depolarized contractions at comparable concentrations in a dose-dependent manner (0.01\u20131\u00a0mg\/mL) similar to papaverine, which is a dual inhibitor of the PDE enzymes and L-type Ca\n                      <jats:sup>++<\/jats:sup>\n                      channels. The indirect functionality of the papaverine-like dual inhibitory actions of the extract was confirmed when pretreatment with the crude extract displaced the Ca\n                      <jats:sup>++<\/jats:sup>\n                      excitatory CRCs to the right with suppression of the maximum response, similar to verapamil; moreover, the PDE inhibitory effect was authenticated by a leftward shift in the isoprenaline-induced inhibitory CRCs. The extract showed bactericidal activity with a resultant minimum inhibitory concentration (MIC) of 550\u00a0\u03bcg\/mL against\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      ,\n                      <jats:italic>Shigella sonnei<\/jats:italic>\n                      , and\n                      <jats:italic>Salmonella typhimurium,<\/jats:italic>\n                      whereas the extended-spectrum \u03b2-lactamase-producing\n                      <jats:italic>E. coli<\/jats:italic>\n                      strain was found to be sensitive to a higher concentration of the extract (MIC of 675\u00a0\u03bcg\/mL).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The present study is a pilot report on the detailed pharmacodynamics of the antispasmodic effects of the crude extract of\n                      <jats:italic>O<\/jats:italic>\n                      .\n                      <jats:italic>fruticosa,<\/jats:italic>\n                      with possible dual inhibition of the Ca\n                      <jats:sup>++<\/jats:sup>\n                      channels and PDE-like effects, which provides a sound basis for its medicinal usage in hyperactive gut disorders. The\n                      <jats:italic>O. fruticosa<\/jats:italic>\n                      extract was further demonstrated to be effective against both enteric and non-enteric pathogens, which might support its use in the treatment of infectious diarrhea.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1790239","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:43:10Z","timestamp":1772602990000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigations of the voltage-gated Ca++ channels and phosphodiesterase enzyme inhibitory-like potential explain the medicinal use of Otostegia fruticosa in diarrhea and hypermotile gut"],"prefix":"10.3389","volume":"17","author":[{"given":"Najeeb Ur","family":"Rehman","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University","place":["Al-Kharj, Saudi Arabia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohd Nazam","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University","place":["Al-Kharj, Saudi Arabia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nasser Abdulaziz","family":"Alalaiwah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University","place":["Al-Kharj, Saudi Arabia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eyad Omar","family":"Alotibi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University","place":["Al-Kharj, Saudi Arabia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aman","family":"Karim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National University of Medical Sciences Rawalpindi","place":["Rawalpindi, Pakistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiegist","family":"Bahta","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Health Sciences, Aksum University","place":["Aksum, Ethiopia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalil Y.","family":"Abujheisha","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Science, Faculty of Medicine and Health Science, Palestine Polytechnic University","place":["Hebron, Palestine"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Noman","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Quaid-i-Azam University Islamabad","place":["Islamabad, Pakistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1080\/10412905.1995.9698522","article-title":"Composition and antimicrobial activity of Otostegia fruticosa forssk","volume":"7","author":"Aboutabl","year":"1995","journal-title":"J. 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