Esculentoside A alleviates intestinal dysmotility in acute pancreatitis with potential involvement of the NF-κB/nNOS pathway in enteric neurons
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.
Related
- Punicalagin Alleviates Diabetic Kidney Injury: Potential Involvement of SESN2-Related Mitophagy and Changes in Pyroptosis-/Ferroptosis-Related Indicators
- β‐sitosterol Alleviates Pulmonary Arterial Hypertension in Rats With Involvement of the VEGF/PI3K/AKT Signaling Pathway
- Re-Du-Ning Alleviates Airway-Intestinal Inflammation of COPD Rats by Regulating Glycerophospholipid Metabolism and Modulating Gut Microbiome
- Heat-Inactivated Lacticaseibacillus paracasei PC-01 Alleviates DSS-Induced Colitis in Mice by Modulating Gut Microbiota and Intestinal Barrier Function
- Microstructural changes in the small bowel wall as the basis for the development of intestinal failure syndrome in acute pancreatitis
BibTeX
@article{cao2026esculentoside,
title = {{Esculentoside A alleviates intestinal dysmotility in acute pancreatitis with potential involvement of the NF-κB/nNOS pathway in enteric neurons}},
author = {Jie Cao and Chunxiang Zhang and Huan Liu and Cuiping Pan and Ribin Liao and Xingyou Li and Shiwei Liang and Haicheng Fang and Ying Liu},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1990314},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1990314},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Esculentoside A alleviates intestinal dysmotility in acute pancreatitis with potential involvement of the NF-κB/nNOS pathway in enteric neurons
AU - Jie Cao
AU - Chunxiang Zhang
AU - Huan Liu
AU - Cuiping Pan
AU - Ribin Liao
AU - Xingyou Li
AU - Shiwei Liang
AU - Haicheng Fang
AU - Ying Liu
PY - 2026
DA - 2026/11/09
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1990314
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1990314
AB - 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.
SN - 1663-9812
ER -