{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:08:21Z","timestamp":1788761301228,"version":"build-2803163510"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070554"],"award-info":[{"award-number":["82070554"]}],"id":[{"id":"10.13039\/501100001809","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>Slow transit constipation (STC) is characterized by delayed intestinal transit and impaired defecation, with enteric nervous system (ENS) injury and inflammatory dysregulation contributing to its pathogenesis. Acteoside (ACT), a natural phenylethanoid glycoside, has anti-inflammatory and neuroprotective properties. However, its therapeutic effect and mechanism in STC remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The effects of ACT were investigated in a loperamide (LOP)-induced STC-like mouse model. Intestinal motility, colonic morphology, and ENS integrity were evaluated by functional assays, hematoxylin and eosin (H&amp;amp;E) staining, and immunofluorescence. Transcriptomic analysis was performed to screen ACT-responsive inflammatory pathways. NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and cytokine production were assessed by Western blotting, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (qRT-PCR).\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      -knockout (\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      -KO) mice were used for genetic validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ACT shortened defecation latency, increased fecal water content and pellet number, and improved intestinal propulsion. ACT also alleviated colonic histopathological injury, restored muscular layer thickness, preserved HuC\/D-positive myenteric neurons, and increased PGP9.5-positive nerve fiber density. Transcriptomic analysis identified NLRP3-related inflammatory signaling within broader high-dose ACT-responsive transcriptional changes. At the molecular level, high-dose ACT reduced the protein levels of NLRP3, cleaved-caspase-1, and cleaved-interleukin-1\u03b2 (IL-1\u03b2) expression and reduced IL-1\u03b2, interleukin-6 (IL-6), and tumor necrosis factor-\u03b1 (TNF-\u03b1) production.\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      deficiency partially reproduced ACT-mediated protection against STC-like phenotypes, inflammasome activation, and ENS injury, whereas ACT retained additional protective effects in\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      -KO mice, suggesting that NLRP3-independent mechanisms may also contribute.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ACT alleviates LOP-induced STC-like injury, and this protection is associated with attenuation of NLRP3 inflammasome activation and preservation of ENS integrity, while additional NLRP3-independent mechanisms may also contribute.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1921808","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:34:33Z","timestamp":1788759273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Acteoside alleviates slow transit constipation with attenuation of NLRP3 inflammasome activation and preservation of enteric neurons"],"prefix":"10.3389","volume":"17","author":[{"given":"Baohong","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Ping","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangxu","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Yuhuangding Hospital","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"72","DOI":"10.4291\/wjgp.v2.i5.72","article-title":"Cytokine-induced alterations of gastrointestinal motility in gastrointestinal disorders","volume":"2","author":"Akiho","year":"2011","journal-title":"World Journal Gastrointestinal Pathophysiology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1053\/j.gastro.2019.12.034","article-title":"Mechanisms, evaluation, and management of chronic constipation","volume":"158","author":"Bharucha","year":"2020","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"936","DOI":"10.14309\/ajg.0000000000002227","article-title":"American gastroenterological association-american college of gastroenterology clinical practice guideline: pharmacological management of chronic idiopathic constipation","volume":"118","author":"Chang","year":"2023","journal-title":"Am. 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