Neurogastroenterology and Motility最新文献

{"title":"Current Strategies and Future Perspectives in the Management of Opioid-Induced Constipation: A Review of International and Japanese Guidelines.","authors":"Noriaki Manabe, Eikichi Ihara, Kinomi Yomiya, Masako Iseki, Akira Torii, Hiroto Miwa, Michael Camilleri","doi":"10.1111/nmo.70343","DOIUrl":"https://doi.org/10.1111/nmo.70343","url":null,"abstract":"<p><strong>Background: </strong>Opioids are indicated for pain that occurs with cancer and other disorders that become more prevalent with aging. The most prevalent and persistent adverse effect of opioid therapy is opioid-induced constipation (OIC). OIC impairs patient quality of life (QoL) and leads to suboptimal pain management due to medication non-adherence. Unlike other adverse effects, OIC persists and is not associated with pharmacological tolerance, necessitating long-term management.</p><p><strong>Objectives: </strong>The objective of this study is to evaluate current clinical strategies for OIC by comparing recommendations from American, European, and Japanese clinical guidelines. We reviewed the clinical evidence for the peripherally acting μ-opioid receptor antagonist (PAMORA) naldemedine (the only PAMORA approved in Japan) and the rationale for early intervention in OIC.</p><p><strong>Methods: </strong>The clinical guidelines and recent clinical trial data, including the COMPOSE program (phase III clinical trials of naldemedine for OIC in patients with chronic non-cancer pain), were reviewed to establish an evidence-based framework for the management of chronic cancer and non-cancer pain.</p><p><strong>Results: </strong>Conventional laxatives frequently provide inadequate relief as they address secondary symptoms rather than the underlying receptor-mediated cause. PAMORAs (including naldemedine, methyl naltrexone, and naloxegol) antagonize gastrointestinal opioid receptors without compromising central analgesia. Early initiation of PAMORAs stabilizes bowel function and reduces the incidence of treatment-related diarrhea that occurs when using conventional laxatives to treat OIC.</p><p><strong>Conclusion: </strong>The 2023 Japanese guidelines advocate the proactive use of the PAMORA naldemedine as a primary treatment option. This mechanism-based early intervention model offers a promising framework for optimizing QoL and implementing effective analgesia in an aging global population.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 5","pages":"e70343"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Site Proteomics Reveals Distinct Molecular Patterns Within Functional Dyspepsia.","authors":"Ruiqi Ma, Qianjun Zhuang, Zhanye Zhang, Junnan Hu, Yubin Xie, Niandi Tan, Mengyu Zhang, Yinglian Xiao","doi":"10.1111/nmo.70333","DOIUrl":"https://doi.org/10.1111/nmo.70333","url":null,"abstract":"<p><strong>Background: </strong>Functional dyspepsia (FD) is a common gastrointestinal disorder lacking established molecular targets. Symptom-based classification into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) often fails to guide effective therapy.</p><p><strong>Objective: </strong>To identify molecular subtypes of FD using proteomics to better understand disease heterogeneity.</p><p><strong>Methods: </strong>Using 4D-DIA proteomics, we analyzed gastric and duodenal biopsies from 47 FD patients and 10 healthy controls. Non-negative matrix factorization was applied separately to each site for unsupervised clustering. Subtypes were characterized by clinical profiles, pathway enrichment, immune infiltration analysis, and validated via histology and immunostaining.</p><p><strong>Results: </strong>Two gastric (G1: 17%, G2: 83%) and three duodenal subtypes (D1: 13%, D2: 70%, D3: 17%) were identified. G1 showed strong immune activation linked to H. pylori infection, while G2 was enriched for metabolic pathways. Duodenal subtypes revealed distinct mechanisms: D1 featured eosinophil-predominant inflammation, D2 showed ROS metabolism and ferroptosis correlated with pain, and D3 exhibited mast cell infiltration. Gastric and duodenal subtypes were independent of each other. No significant association was found between molecular subtypes and EPS/PDS clinical classification.</p><p><strong>Conclusion: </strong>FD involves heterogeneous molecular mechanisms across gastric and duodenal sites. Duodenal profiling exhibited disease-relevant immune and oxidative pathways, while gastric patterns are largely distinguished by H. pylori infection status. Conventional symptom-based subtyping fails to capture this complexity, underscoring the need for mechanism-based stratification to guide personalized treatment in FD.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 5","pages":"e70333"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Mixed-Methods Analysis of Trauma-Exposed Adolescents' Gastrointestinal Symptoms as Captured in Online Social Communication.","authors":"Katherine M Ingram, Allegra S Anderson, Dimitri Luzincourt, Stephanie Chun, Irina Gorbounova, Sachin Pendse, Jason Shapiro, Jeff Huang, Nicole R Nugent","doi":"10.1111/nmo.70326","DOIUrl":"https://doi.org/10.1111/nmo.70326","url":null,"abstract":"<p><strong>Background: </strong>Traumatic stress can disrupt the adolescent gut-brain axis, and unintentional social reinforcement can lead to highly impairing disorders of gut-brain interaction (DGBI). However, social support is critical during the peritraumatic period, highlighting a unique challenge for caregivers and practitioners. The current study examined the ways in which post-trauma gastrointestinal concerns were discussed via online social messaging (e.g., texting, social media) among a sample of trauma-exposed adolescent patients.</p><p><strong>Methods: </strong>One hundred ninety-one trauma-exposed adolescents were recruited from a US children's hospital emergency department. Topic modeling and key-word identification were used to examine naturalistic online communication (e.g., text messages), yielding a subsample of youth who used online social messaging to communicate about their gastrointestinal symptoms. Inductive content analysis was used to characterize communication about GI symptoms during the nine-month period immediately following presentation for a potentially traumatic event.</p><p><strong>Key results: </strong>Youth were most likely to share about symptoms with peers (i.e., friends, romantic partners) rather than adults. Responses were usually caring/affirming or offered practical support; dismissive responses were rare. GI symptoms and life stressors were often mentioned in the same conversation. Themes of avoidance and impairment were also identified.</p><p><strong>Conclusions and inferences: </strong>Findings demonstrate the role of digital social attention in illness reinforcement, which complicates social support during the peritraumatic period. This avenue for peer reinforcement should be considered in treatment planning and discussions of family guidelines for managing symptoms.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 5","pages":"e70326"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optical Mapping of Pacing-Elicited Slow Waves in the Swine Stomach: Role of Virtual Electrodes.","authors":"Hanyu Zhang, Haley N Patton, Nipuni D Nagahawatte, Bijay Guragain, Leo K Cheng, Gregory P Walcott, Jack M Rogers","doi":"10.1111/nmo.70340","DOIUrl":"10.1111/nmo.70340","url":null,"abstract":"<p><strong>Background: </strong>Stomach contractions are coordinated in part by bioelectric slow waves (SW). Dysfunctional SWs are associated with motility disorders. Electrical pacing is a potential strategy for managing motility disorders but remains poorly understood with inconsistent efficacy.</p><p><strong>Methods: </strong>We used a newly-developed optical mapping method to image gastric pacing in 4 pigs (35.0 ± 1.3 kg). The method imaged transmembrane potential, primarily from the circular smooth muscle layer, with high spatiotemporal resolution. We delivered unipolar pacing pulses to the serosal surface or to the luminal side of the circular muscle layer. Pulses were 100 ms in duration with 4 or 8 mA amplitude.</p><p><strong>Key results: </strong>Pacing elicited transmembrane potential polarization patterns consistent with bidomain theory: For cathodal pacing, there was an elongated depolarized region (virtual cathode) oriented orthogonally to the smooth muscle fibers and centered on the electrode. It was flanked on either side by hyperpolarized virtual anodes. For anodal pacing, virtual electrode polarity was reversed. Of 175 pulses, 18% induced SWs that activated the entire mapping region. The remaining pulses failed completely (38%) or induced SWs that only partially activated the mapping region (43%). All SWs initiated from virtual cathode sites approximately 1 cm from the pacing electrode and not from the electrode site itself.</p><p><strong>Conclusions and inferences: </strong>These results suggest that close to the electrode, pacing pulses inhibited the network of interstitial cells of Cajal (ICC) that propagates SW. SWs may have initiated when the ICC network was activated by depolarized smooth muscle in the virtual cathodes remote from the electrode.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 5","pages":"e70340"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Online Group Hypnotherapy for Irritable Bowel Syndrome-a Pilot Study.","authors":"Jenny Lövdahl, Hans Törnblom, Gisela Ringström, Olafur S Palsson, Magnus Simrén","doi":"10.1111/nmo.70328","DOIUrl":"10.1111/nmo.70328","url":null,"abstract":"<p><strong>Background: </strong>Gut-directed hypnotherapy is an effective treatment for patients with irritable bowel syndrome (IBS). Group delivery and nurse-led hypnotherapy can increase availability. Online treatment shows promising results, but this has not been tested in a group format.</p><p><strong>Aims: </strong>To investigate the acceptability and efficacy of nurse-led, online group hypnotherapy in patients with IBS.</p><p><strong>Methods: </strong>Patients received eight sessions of gut-directed hypnotherapy in groups via live video conferencing. IBS symptoms were assessed at baseline, mid-treatment, after treatment, and at follow-up. Patients who reported an IBS-SSS reduction of ≥ 50 points were considered responders. Extracolonic symptoms, psychological symptoms, and quality of life were assessed, as well as usability and treatment satisfaction. The study results were compared to previous assessments of group hypnotherapy delivered on-site. After hypnotherapy, patients were asked which treatment modality (online or on-site) they would prefer.</p><p><strong>Results: </strong>We included 51 patients. IBS severity was reduced after hypnotherapy (median IBS-SSS: 304 (225-385) vs. 225 (172-312), p < 0.001), and 27 patients (53%) were responders. These results are comparable to on-site group hypnotherapy outcomes; IBS-SSS: 310 (232-368) versus 230 (151-330), p < 0.001, responders: 55%. Symptom reduction was sustained at six-month follow-up. Quality of life, extracolonic, and psychological symptoms also improved. The patient ratings of the usability of the video call platform and treatment satisfaction were high.</p><p><strong>Conclusions and inferences: </strong>Nurse-led, gut-directed group hypnotherapy delivered online is acceptable, often preferred by patients, and has comparable efficacy to in-person group hypnotherapy. By combining group and online treatment, hypnotherapy can be made more accessible for patients.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 5","pages":"e70328"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge Does Not Translate Into Diagnostic Restraint: Application of Rome-Based IBS Diagnosis Among Medical Students in Latin America.","authors":"Manuel Linares, Catalina Grimaldi, Natalia Palma, Bryan Vintimilla, Sofia Candal, David Estrella, Miguel Saps","doi":"10.1111/nmo.70335","DOIUrl":"10.1111/nmo.70335","url":null,"abstract":"<p><strong>Background: </strong>Disorders of gut-brain interaction (DGBIs) are highly prevalent and frequently evaluated using a positive, symptom-based diagnostic framework defined by the Rome criteria. Despite guideline recommendations discouraging routine exclusionary testing in the absence of alarm features, excessive diagnostic evaluation remains common in clinical practice. Whether this pattern originates during undergraduate medical training is unknown.</p><p><strong>Methods: </strong>We conducted a multicenter cross-sectional study of 238 medical students from 45 universities across 14 Latin American countries. Participants completed a structured survey assessing exposure to DGBI teaching, theoretical knowledge of Rome-based diagnosis, recognition of alarm features, and diagnostic decision-making using sequential standardized vignettes representing a Rome IV-consistent irritable bowel syndrome (IBS) presentation without red flags.</p><p><strong>Results: </strong>Although 74% reported prior DGBI-specific teaching and 69% had heard of the Rome criteria, 70% ordered diagnostic tests in the initial Rome-consistent adult vignette. Testing escalated with increased symptom severity and persisted in 53% despite normal laboratory findings. Misclassification of functional symptoms as alarm features occurred in approximately one-third of respondents. Higher theoretical knowledge was associated with lower initial testing rates (68% vs. 83%, p = 0.010), although unnecessary testing remained common even among high-knowledge students. Only 15% met criteria for high composite clinical performance, and 21% demonstrated discordant high knowledge but poor clinical reasoning.</p><p><strong>Conclusions: </strong>These findings identify an early divergence between Rome-based diagnostic principles and applied clinical reasoning. Diagnostic overuse in DGBIs may begin during undergraduate training, suggesting that improving education requires not only knowledge transmission but also structured reinforcement of positive diagnosis and diagnostic restraint.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 5","pages":"e70335"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13145304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to V. Martín-Dominguez Et Al.: Re-Evaluating the Diagnostic Approach to Lactose Malabsorption.","authors":"C Hermida Díaz, B Pascual Miguel, C Ferreras Puente","doi":"10.1111/nmo.70217","DOIUrl":"10.1111/nmo.70217","url":null,"abstract":"<p><strong>Background: </strong>The article by Martín-Domínguez V et al. proposes genetic testing as the first diagnostic test for lactose malabsorption, given its high concordance with the lactose breath test (LBT). We think that conceptual and methodological inconsistencies undermine this conclusion.</p><p><strong>Methods: </strong>The genetic test, LBT, and Gaxilose test measure different physiological aspects such as genetic predisposition, lactose malabsorption, and lactase enzymatic activity, respectively, so the three tests cannot be used interchangeably. Diagnostic bias is introduced by the study's limited use of biopsy confirmation, disregard for secondary hypolactasia, and reliance on genotype as a reference standard.</p><p><strong>Results: </strong>Additionally, the clinical validity of the results is compromised by the high variability in genetic polymorphisms across populations, unreported comorbidities like SIBO or IBS, and dubious symptom assessment during testing. Evidence from multicenter studies demonstrates that the Gaxilose test offers high sensitivity and specificity and is well tolerated.</p><p><strong>Conclusions: </strong>We conclude that genetic testing alone cannot replace functional or structural assessments and warn that the study's conclusions may lead to misleading diagnostic recommendations in real-world clinical practice.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":" ","pages":"e70217"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insomnia, A Comorbidity to Take Into Account in the Global Management of Patients With Irritable Bowel Syndrome?","authors":"Eline Albert, Hiba Mikhael-Moussa, Fabien Wuestenberghs, Anne-Marie Leroi, Marie Netchitailo, Guillaume Gourcerol, Inês A Trindade, Charlotte Desprez, Chloé Melchior","doi":"10.1111/nmo.70336","DOIUrl":"https://doi.org/10.1111/nmo.70336","url":null,"abstract":"<p><strong>Introduction: </strong>In the general population, many people are affected by both insomnia and irritable bowel syndrome (IBS). In this study, we aimed to explore the prevalence of insomnia in patients with IBS and its association with the severity of gastrointestinal and extra-intestinal symptoms.</p><p><strong>Methods: </strong>Patients with IBS according to Rome IV criteria, referred to the Physiology Unit of Rouen University Hospital (France) between September 2022 and February 2025, who completed various validated questionnaires during their visit to assess insomnia (Insomnia Severity Index (ISI)), IBS severity (IBS-SSS), anxiety and depressive symptoms (HAD-S), quality of life (IBS-QOL), upper gastrointestinal symptom severity (PAGI-SYM), and somatic symptom severity (PHQ-15), were prospectively included in our study. Patients were considered insomniacs when their ISI score was ≥ 15.</p><p><strong>Results: </strong>Among 700 patients with IBS included in our analysis, 270 (38.6%) were insomniac. The presence of insomnia was associated with more severe gastrointestinal symptoms (IBS severity, IBS-SSS, p < 0.001) and somatic symptom severity (PHQ-15, p < 0.001). The hierarchical linear regression analysis showed that the ISI score was associated with higher scores of anxiety and depressive symptoms, the presence of functional dyspepsia and fibromyalgia, and, to a lesser extent, older age and higher IBS severity scores (Adjusted R² = 0.265).</p><p><strong>Discussion: </strong>Our findings suggest that in patients with IBS, insomnia is linked with psychological and somatic symptom burden, and the presence of comorbidities such as functional dyspepsia, but causality cannot be inferred. Future studies using objective sleep assessments, such as polysomnography, are needed to confirm these associations.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 5","pages":"e70336"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Primer for Discussing Complementary and Integrative Medicine in Gastroenterology Settings.","authors":"Elyse R Thakur, Meredith Craven, Laurie Keefer, David J Hass","doi":"10.1111/nmo.70313","DOIUrl":"https://doi.org/10.1111/nmo.70313","url":null,"abstract":"<p><strong>Background: </strong>Complementary and integrative medicine interventions have been increasingly utilized among patients with chronic gastrointestinal disorders. However, to date, there is no data on the implementation of these approaches as part of gastroenterology consultations and follow-up visits, which suggests that gastroenterology professionals may need more guidance on how to routinely engage in discussions about complementary and integrative medicine approaches to promote best practice.</p><p><strong>Purpose: </strong>This article aims to provide practical recommendations for gastroenterology professionals on how to initiate and navigate discussions about the use of complementary and integrative medicine interventions for patients in routine GI practice settings.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 4","pages":"e70313"},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antidiarrheal Potential of Psoralidin Through Modulation of COX, μ-Opioid, and L-Type Calcium Channel Signaling Pathways: In Vivo and In Silico Investigations.","authors":"Sonaly Akter Mukty, Razina Rouf, Tawfik Rakaiyat Ripu, Md Shakil Ahmmed, Mohammad Y Alshahrani, Md Nasimul Haque Shipon, Mahamuda Khatun, Md Arif Hossain, Emon Mia, Md Sakib Al Hasan, Muhammad Torequl Islam","doi":"10.1111/nmo.70290","DOIUrl":"https://doi.org/10.1111/nmo.70290","url":null,"abstract":"<p><strong>Background: </strong>Psoralidin (PSN), a prenylated coumestrol, demonstrates a broad spectrum of pharmacological properties, such as anti-inflammatory, anticancer, anti-diabetic, and neuroprotective activities. This study aimed to evaluate the therapeutic potential of PSN as an antidiarrheal agent using in vivo experimentation in a castor oil-induced chick model, supported by in silico receptor-binding analyses.</p><p><strong>Methods: </strong>Chicks were treated orally with PSN at doses of 5, 15, and 30 mg/kg and compared with standard reference drugs, including bismuth subsalicylate (BSS, 10 mg/kg), loperamide (LOP, 3 mg/kg), and nifedipine (NFN, 2.5 mg/kg). Diarrheal onset, stool frequency, and intestinal fluid secretion were recorded. Complementary molecular docking, pharmacokinetic, and toxicity assessments were performed to predict drug-receptor interactions and safety profiles.</p><p><strong>Results: </strong>Among all treatment groups, PSN-15 at its most effective dose produced the most significant reduction in parameters, lowering the diarrheal secretion (DRS) score to 138.00 ± 2.91 mg and the number of stool output (NSO) to 6.80 ± 1.09 events compared to the NC group. In silico analysis demonstrated that PSN formed stable binding complexes with high binding affinity (BA) for cyclooxygenase-2 (COX-2) (-9.2 kcal/mol), as well as for μ-opioid receptor, COX-1, and L-type calcium channel. Computational toxicity profiling suggests a favorable preliminary safety profile for PSN.</p><p><strong>Conclusion: </strong>In conclusion, PSN demonstrated significant antidiarrheal activity by reducing stool frequency, intestinal secretion, and delaying onset of diarrhea, likely through multi-target modulation of COX, μ-opioid, and L-type calcium channel pathways. Nonetheless, future studies will focus on detailed pharmacokinetic profiling, long-term toxicity assessment, and validation of PSN's antidiarrheal efficacy in advanced preclinical models to support its therapeutic potential.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":"38 4","pages":"e70290"},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}