从肠脑轴探讨功能性腹泻、显性腹泻型肠易激综合征、功能性消化不良的共病机制及参灵百助散的药理作用机制

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Chunfeng Mei, Lili Han, Hong Xue
{"title":"从肠脑轴探讨功能性腹泻、显性腹泻型肠易激综合征、功能性消化不良的共病机制及参灵百助散的药理作用机制","authors":"Chunfeng Mei, Lili Han, Hong Xue","doi":"10.2174/0113862073329698250102120037","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Functional Diarrhea (FDr), Irritable Bowel Syndrome with predominant diarrhea (IBS-D), and Functional Dyspepsia (FD) are common functional gastrointestinal disorders (FGIDs) with significant impacts on quality of life. While the gut-brain axis and key regulators like 5-hydroxytryptamine (5-HT), dopamine (DA), and butyrate are known to play crucial roles in these conditions, the mechanisms underlying their comorbidities remain unclear. Shen-Ling-Bai-Zhu-San (SLBZS), a traditional herbal formula, is effective in treating FGIDs. Still, the specific components and mechanisms mediating its therapeutic effects via the gut-brain axis are not well understood.</p><p><strong>Methods: </strong>This study identified molecular links among FDr, IBS-D, and FD from the gut-brain axis using integrated biological information. The pharmacological mechanisms of SLBZS were explored through network pharmacology, molecular docking, molecular dynamics simulations, and in vitro bio-layer interferometry (BLI) validation.</p><p><strong>Results: </strong>A total of 328 common targets were identified among FDr, IBS-D, and FD, with 22 hub genes in the protein-protein interaction (PPI) network associated with 5-HT/DA/butyrate pathways. Virtual screening revealed seven key targets (AKT1, CASP3, VEGFA, INS, CTNNB1, PTGS2, and IL1B) and 14 bioactive components (e.g., diosgenin and luteolin) from SLBZS. Molecular docking indicated strong binding affinities between key components and targets, while molecular dynamics simulations confirmed stable interactions, particularly between PTGS2 and diosgenin/luteolin. BLI experiments further validated the strong binding affinity of PTGS2 for diosgenin.</p><p><strong>Conclusion: </strong>This study elucidates potential targets shared by FDr, IBS-D, and FD through the gut-brain axis, highlighting diosgenin's interaction with PTGS2 as a potential mechanism of SLBZS's therapeutic effects. These findings provide valuable insights into the pharmacological mechanisms of SLBZS in treating FGIDs and suggest new avenues for targeted therapies.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring the Comorbidity Mechanism among Functional Diarrhea, Irritable Bowel Syndrome with Predominant Diarrhea, and Functional Dyspepsia through the Gut-brain Axis and the Pharmacological Mechanisms of Shen-Ling-Bai-Zhu-San Therapy.\",\"authors\":\"Chunfeng Mei, Lili Han, Hong Xue\",\"doi\":\"10.2174/0113862073329698250102120037\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Functional Diarrhea (FDr), Irritable Bowel Syndrome with predominant diarrhea (IBS-D), and Functional Dyspepsia (FD) are common functional gastrointestinal disorders (FGIDs) with significant impacts on quality of life. While the gut-brain axis and key regulators like 5-hydroxytryptamine (5-HT), dopamine (DA), and butyrate are known to play crucial roles in these conditions, the mechanisms underlying their comorbidities remain unclear. Shen-Ling-Bai-Zhu-San (SLBZS), a traditional herbal formula, is effective in treating FGIDs. Still, the specific components and mechanisms mediating its therapeutic effects via the gut-brain axis are not well understood.</p><p><strong>Methods: </strong>This study identified molecular links among FDr, IBS-D, and FD from the gut-brain axis using integrated biological information. The pharmacological mechanisms of SLBZS were explored through network pharmacology, molecular docking, molecular dynamics simulations, and in vitro bio-layer interferometry (BLI) validation.</p><p><strong>Results: </strong>A total of 328 common targets were identified among FDr, IBS-D, and FD, with 22 hub genes in the protein-protein interaction (PPI) network associated with 5-HT/DA/butyrate pathways. Virtual screening revealed seven key targets (AKT1, CASP3, VEGFA, INS, CTNNB1, PTGS2, and IL1B) and 14 bioactive components (e.g., diosgenin and luteolin) from SLBZS. Molecular docking indicated strong binding affinities between key components and targets, while molecular dynamics simulations confirmed stable interactions, particularly between PTGS2 and diosgenin/luteolin. BLI experiments further validated the strong binding affinity of PTGS2 for diosgenin.</p><p><strong>Conclusion: </strong>This study elucidates potential targets shared by FDr, IBS-D, and FD through the gut-brain axis, highlighting diosgenin's interaction with PTGS2 as a potential mechanism of SLBZS's therapeutic effects. These findings provide valuable insights into the pharmacological mechanisms of SLBZS in treating FGIDs and suggest new avenues for targeted therapies.</p>\",\"PeriodicalId\":10491,\"journal\":{\"name\":\"Combinatorial chemistry & high throughput screening\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-04-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Combinatorial chemistry & high throughput screening\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0113862073329698250102120037\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Combinatorial chemistry & high throughput screening","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0113862073329698250102120037","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0

摘要

背景:功能性腹泻(FDr)、肠易激综合征伴主要腹泻(IBS-D)和功能性消化不良(FD)是常见的功能性胃肠道疾病(fgid),对生活质量有显著影响。虽然已知肠-脑轴和5-羟色胺(5-HT)、多巴胺(DA)和丁酸盐等关键调节因子在这些疾病中起着关键作用,但其合并症的机制尚不清楚。参灵百珠散是一种治疗FGIDs的传统中药配方。然而,通过肠脑轴介导其治疗效果的具体成分和机制尚不清楚。方法:本研究利用综合生物学信息从肠脑轴上确定FDr、IBS-D和FD之间的分子联系。通过网络药理学、分子对接、分子动力学模拟、体外生物层干涉法(BLI)验证等方法探讨了SLBZS的药理机制。结果:FDr、IBS-D和FD共鉴定出328个共同靶点,其中蛋白蛋白相互作用(PPI)网络中与5-HT/DA/丁酸途径相关的枢纽基因有22个。虚拟筛选从SLBZS中发现了7个关键靶点(AKT1, CASP3, VEGFA, INS, CTNNB1, PTGS2和IL1B)和14个生物活性成分(如薯蓣皂苷元和木草素)。分子对接表明关键组分与靶点之间具有很强的结合亲和力,而分子动力学模拟证实了稳定的相互作用,特别是PTGS2与薯蓣皂苷元/木犀草素之间的相互作用。BLI实验进一步验证了PTGS2对薯蓣皂苷元的强结合亲和力。结论:本研究阐明了FDr、IBS-D和FD通过肠-脑轴共同的潜在靶点,突出了薯蓣皂苷元与PTGS2的相互作用可能是SLBZS治疗效果的潜在机制。这些发现为SLBZS治疗FGIDs的药理学机制提供了有价值的见解,并为靶向治疗提供了新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring the Comorbidity Mechanism among Functional Diarrhea, Irritable Bowel Syndrome with Predominant Diarrhea, and Functional Dyspepsia through the Gut-brain Axis and the Pharmacological Mechanisms of Shen-Ling-Bai-Zhu-San Therapy.

Background: Functional Diarrhea (FDr), Irritable Bowel Syndrome with predominant diarrhea (IBS-D), and Functional Dyspepsia (FD) are common functional gastrointestinal disorders (FGIDs) with significant impacts on quality of life. While the gut-brain axis and key regulators like 5-hydroxytryptamine (5-HT), dopamine (DA), and butyrate are known to play crucial roles in these conditions, the mechanisms underlying their comorbidities remain unclear. Shen-Ling-Bai-Zhu-San (SLBZS), a traditional herbal formula, is effective in treating FGIDs. Still, the specific components and mechanisms mediating its therapeutic effects via the gut-brain axis are not well understood.

Methods: This study identified molecular links among FDr, IBS-D, and FD from the gut-brain axis using integrated biological information. The pharmacological mechanisms of SLBZS were explored through network pharmacology, molecular docking, molecular dynamics simulations, and in vitro bio-layer interferometry (BLI) validation.

Results: A total of 328 common targets were identified among FDr, IBS-D, and FD, with 22 hub genes in the protein-protein interaction (PPI) network associated with 5-HT/DA/butyrate pathways. Virtual screening revealed seven key targets (AKT1, CASP3, VEGFA, INS, CTNNB1, PTGS2, and IL1B) and 14 bioactive components (e.g., diosgenin and luteolin) from SLBZS. Molecular docking indicated strong binding affinities between key components and targets, while molecular dynamics simulations confirmed stable interactions, particularly between PTGS2 and diosgenin/luteolin. BLI experiments further validated the strong binding affinity of PTGS2 for diosgenin.

Conclusion: This study elucidates potential targets shared by FDr, IBS-D, and FD through the gut-brain axis, highlighting diosgenin's interaction with PTGS2 as a potential mechanism of SLBZS's therapeutic effects. These findings provide valuable insights into the pharmacological mechanisms of SLBZS in treating FGIDs and suggest new avenues for targeted therapies.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信