{
  "abstract": "BackgroundEsculentoside A (EsA), a triterpenoid saponin from Phytolacca esculenta roots, exerts anti-inflammatory, antitumor, and other pharmacological effects. However, its role in AP-related intestinal motility disorders rema1ins unexplored. The mechanism underlying intestinal dysmotility in acute pancreatitis (AP) remains unclear, with enteric neurons (ENs) playing a primary role. This study aimed to investigate the mechanism of intestinal dysmotility in AP and explore the therapeutic potential of EsA intervention.MethodsAn in vivo rat model of AP was established, together with in vitro AP models using co-cultured ENs and intestinal smooth muscle cells (ISMCs), followed by EsA intervention. Differential proteins were screened via proteomics and subjected to bioinformatic analysis. Intestinal motility was evaluated by detecting the contractile activity of colonic smooth muscle strips, fecal pellet counts, as well as the contractile activity and migratory capacity of ISMCs. Nitric oxide (NO) levels were measured. Immunofluorescence and immunohistochemistry were used to determine the number of nNOS-positive neurons, nNOS expression, and NF-κB p65 nuclear translocation. Western blotting was performed to detect the protein levels of PI3K/Akt/NF-κB/nNOS signaling-related molecules.ResultsLC-MS/MS proteomic analysis revealed significant enrichment of NF-κB and PI3K/Akt pathways in the muscularis of AP rats. Both in vivo and in vitro experiments during AP demonstrated activation of the PI3K/Akt/NF-κB/nNOS pathways, manifested by elevated p-PI3K, p-Akt, p-IKKβ, p-NF-κB p65, and p-IκBα levels, increased IκBα degradation, enhanced NF-κB p65 nuclear translocation, and upregulation of nNOS expression and nNOS-positive neuronal counts, thereby promoting NO production. This inhibited the contractile activity and migratory capacity of ISMCs, ultimately reducing rat fecal pellet counts in rats and decreasing the contractile activity of colonic muscle strips. EsA intervention contributed to downregulating the nuclear translocation of NF-κB p65, nNOS expression, and NO levels in ENs, thereby improving ISMC function.ConclusionAberrant activation of the PI3K/Akt/NF-κB/nNOS pathway may contribute to the pathogenesis of intestinal dysmotility in AP. EsA may reduce NO production, presumably by suppressing the NF-κB/nNOS axis, thereby ameliorating AP-associated intestinal dysmotility.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Jie Cao"
    },
    {
      "name": "Chunxiang Zhang"
    },
    {
      "name": "Huan Liu"
    },
    {
      "name": "Cuiping Pan"
    },
    {
      "name": "Ribin Liao"
    },
    {
      "name": "Xingyou Li"
    },
    {
      "name": "Shiwei Liang"
    },
    {
      "name": "Haicheng Fang"
    },
    {
      "name": "Ying Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/by76w6wbvv98d.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1990314",
  "fulltext_url": null,
  "id": "by76w6wbvv98d",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1990314",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "medicine/pharmacology-toxicology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-09",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/by76w6wbvv98d.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:20:33Z",
      "native_id": "10.3389/fphar.2026.1990314",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1990314"
    },
    {
      "first_seen": "2026-11-09T12:23:31Z",
      "native_id": "10.3389/fphar.2026.1990314",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1990314/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Esculentoside A alleviates intestinal dysmotility in acute pancreatitis with potential involvement of the NF-κB/nNOS pathway in enteric neurons",
  "title_text": "Esculentoside A alleviates intestinal dysmotility in acute pancreatitis with potential involvement of the NF-κB/nNOS pathway in enteric neurons",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:41Z",
  "url": "https://research.draconitic.com/paper/by76w6wbvv98d",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}