{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:47:48Z","timestamp":1777769268692,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["nyaspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann NY Acad Sci"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Krisanaklan (KK) is a traditional herbal remedy used to treat an array of gastrointestinal complaints, including infectious, secretory diarrhea (SD). We assessed the effect of KK on anion and fluid secretion across intestinal epithelia, and delineated its mode of action. KK inhibited cholera toxin\/cAMP\u2010dependent anion secretion across intestinal epithelial monolayers and native intestinal epithelium\n                    <jats:italic>ex vivo<\/jats:italic>\n                    . Similarly, KK reduced cAMP\u2010dependent fluid secretion in intestinal organoids. KK inhibited Na\n                    <jats:sup>+<\/jats:sup>\n                    ,K\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase (NKA)\u2010mediated, ouabain\u2010sensitive ion transport and channel\u2010mediated K\n                    <jats:sup>+<\/jats:sup>\n                    efflux across the basolateral plasma membrane but did not block cAMP\u2010dependent anion transport across the apical plasma membrane. KK also inhibited ouabain\u2010insensitive ATPase activity, but did not affect cAMP\u2010dependent protein phosphorylation. KK reduced carrier\u2010mediated amino acid uptake in Caco\u20102 cells and Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2010coupled glucose transport in porcine intestine. Further, KK inhibited cGMP\u2010 and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010linked anion secretion across intestinal epithelial monolayers. We conclude that KK blocks intestinal epithelial anion and fluid secretion by inhibition of the NKA and K\n                    <jats:sup>+<\/jats:sup>\n                    channels. Consequently, KK may ameliorate SD caused by enteric microbial pathogens. However, by inhibiting the activity of Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2010dependent solute carriers, it is also predicted to counteract oral rehydration therapy, the current mainstay for SD therapy.\n                  <\/jats:p>","DOI":"10.1111\/nyas.70152","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T14:40:06Z","timestamp":1765896006000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Krisanaklan Reduces Intestinal Anion and Fluid Secretion Through Inhibition of Na\n                    <sup>+<\/sup>\n                    \/K\n                    <sup>+<\/sup>\n                    \u2010ATPase and K\n                    <sup>+<\/sup>\n                    Channel Activity"],"prefix":"10.1111","volume":"1556","author":[{"given":"Tessa A.","family":"Groeneweg","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erdene","family":"Baigal","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anny","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gert\u2010Jan","family":"Kremers","sequence":"additional","affiliation":[{"name":"Erasmus\u00a0Optical\u00a0Imaging\u00a0Center, Department of Pathology Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel J. 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