{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:11:46Z","timestamp":1776337906711,"version":"3.51.2"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> Slow transit constipation (STC) is a common gastrointestinal disorder characterized by altered gut microbiota and reduced number of enterochromaffin cells (ECs). Astragaloside IV (AS-IV), a low drug permeability saponin, has showed beneficial effects on patients with STC. However, the specific mechanism by which AS-IV regulates STC remains unclear. In this study, we aimed to investigate the effect of AS-IV on STC and its associated mechanisms involving gut microbiota.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The effect of AS-IV on STC was evaluated on STC mice induced with loperamide. We measured defecation frequency, intestinal mobility, ECs loss, and colonic lesions in STC mice treated with AS-IV. We also analyzed the changes in gut microbiota and metabolites after AS-IV treatment. Moreover, we investigated the relationship between specific gut microbes and altered fecal metabolites, such as 3-bromotyrosine (3-BrY). We also conducted <jats:italic>in vitro<\/jats:italic> experiments to investigate the effect of 3-BrY on caspase-dependent apoptosis of ECs and the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> AS-IV treatment promoted defecation, improved intestinal mobility, suppressed ECs loss, and alleviated colonic lesions in STC mice. AS-IV treatment also affected gut microbiota and metabolites, with a significant correlation between specific gut microbes and altered fecal metabolites such as 3-BrY. Furthermore, 3-BrY may potentially reduce caspase-dependent apoptosis of ECs and protect cell survival by inhibiting the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our findings suggest that changes in gut microbiota and ECs mediated the therapeutic effect of STC by AS-IV. These results provide a basis for the use of AS-IV as a prebiotic agent for treating STC. The specific mechanism by which AS-IV regulates gut microbiota and ECs warrants further investigation.<\/jats:p>","DOI":"10.3389\/fphar.2023.1196210","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T15:41:03Z","timestamp":1700754063000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells"],"prefix":"10.3389","volume":"14","author":[{"given":"Xingyang","family":"Wan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaxian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mianling","family":"Mo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhimin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuojie","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guozhong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongcheng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donglin","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"E7632-E7641","DOI":"10.1073\/pnas.1804938115","article-title":"A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release","volume":"115","author":"Alcaino","year":"2018","journal-title":"Proc. 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