{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:24:17Z","timestamp":1784647457686,"version":"3.55.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"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. Med."],"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Functional Constipation (FC) is a common gastrointestinal disorder that imposes a considerable strain on global health. It negatively impacts the quality of life and results in significant healthcare expenditures. Current treatments, such as lifestyle changes and medications, fail to meet patient satisfaction due to efficacy and safety issues. Electroacupuncture (EA), with its precise stimulation control and standardized protocols, shows promise in FC management. However, optimal EA parameters for FC treatment are yet to be established. Our study reviews EA applications in FC to inform a standardized treatment approach and explore EA\u2019s therapeutic mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This comprehensive study utilized research literature from databases including PubMed, Embase, OVID, Web of Science, the Cochrane Library, CNKI, VIP, and Wanfang to perform a descriptive analysis of acupoint selection and EA parameters. It proceeded to analyze high-frequency acupoint groupings and stimulus parameters, followed by the excavation and analysis of core acupoint prescriptions. Subsequent steps integrated potential target identification for these core formulas, the assembly of a \u201ccore acupoint-prescription-target-constipation\u201d network, and the construction of a protein\u2013protein interaction (PPI) network to extract central targets. Additionally, Gene Ontology (GO) and KEGG enrichment analyses were conducted to prognosticate the underlying mechanisms by which EA may exert its therapeutic effects on FC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In our study, we analyzed 141EA prescriptions for FC and identified a core set of acupoints including Tianshu (ST25), Fujie (SP14), Shangjuxu (ST37), and Zusanli (ST36) through data mining. The frequency of use was highest for Tianshu (ST25) with 119 occurrences, followed by Fujie (SP14) with 59, Shangjuxu (ST37) with 42, and Zusanli (ST36) with 23. PPI network analysis revealed key targets such as NFKB1, IL6, MyD88, TLR4, TNF, TLR2, and IL1B. GO and KEGG analyses of 49 constipation-associated targets identified 257 BP, 37 CC, and 41 MF terms, and 154 significant pathways, with the top 20 visualized for further analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The core acupoint prescription of EA for FC can exert its therapeutic effects by acting on multiple targets and pathways synergistically especially on NFKB1, IL6, MyD88, TLR4, TNF, TLR2, and IL1B. The research findings have preliminarily validated the fundamental effects and related mechanisms of EA parameters and core prescriptions, providing direction for further in-depth exploration of the mechanisms of action.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1482066","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T18:23:40Z","timestamp":1733941420000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Research on the mechanism of core acupoints in electroacupuncture for functional constipation based on data mining and network acupuncture"],"prefix":"10.3389","volume":"11","author":[{"given":"Shun Seng","family":"Ong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianjie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canwei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihua","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1016\/S0140-6736(20)32115-2","article-title":"Functional gastrointestinal disorders: advances in understanding and management","author":"Black","year":"2020","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.cgh.2023.08.044","article-title":"Perceptions, definitions, and therapeutic interventions for occasional constipation: a Rome working group consensus document","author":"Brenner","year":"2024","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1007\/s10620-023-08072-3","article-title":"High prevalence of anorectal dysfunction in ambulatory patients with chronic constipation, regardless of colon transit time","author":"Triadafilopoulos","year":"2024","journal-title":"Dig Dis Sci"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1080\/17474124.2020.1708718","article-title":"An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation","author":"Aziz","year":"2020","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"00223","DOI":"10.1053\/j.gastro.2016.02.032","article-title":"Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV","author":"Drossman","year":"2016","journal-title":"Gastroenterology"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"255","DOI":"10.2147\/CEG.S239205","article-title":"The humanistic and economic burden of chronic idiopathic constipation in the USA: a systematic literature review","author":"Nag","year":"2020","journal-title":"Clin Exp Gastroenterol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"467","DOI":"10.51821\/84.3.012","article-title":"The role of neuromodulation in chronic functional constipation: a systematic review","volume":"84","author":"Pauwels","year":"2021","journal-title":"Acta Gastro-Enterol Belg"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1111\/apt.16369","article-title":"Review article: diagnosis, management and patient perspectives of the spectrum of constipation disorders","author":"Sharma","year":"2021","journal-title":"Aliment Pharmacol Ther"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e64","DOI":"10.1097\/MCG.0000000000001473","article-title":"Treatment satisfaction with current medications for chronic constipation: an internet survey of Japanese patients","author":"Hayashi","year":"2022","journal-title":"J Clin Gastroenterol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e23014","DOI":"10.1097\/MD.0000000000023014","article-title":"Electroacupuncture for the treatment of functional dyspepsia: a systematic review and meta-analysis","author":"Mao","year":"2020","journal-title":"Medicine"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"15347354231192017","DOI":"10.1177\/15347354231192017","article-title":"Research on electroacupuncture parameters for cancer pain based on data mining","author":"Li","year":"2023","journal-title":"Integr Cancer Ther"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1007\/s00384-023-04487-6","article-title":"Efficacy and safety of electroacupuncture for secondary constipation: a systematic review and meta-analysis","author":"Jie","year":"2023","journal-title":"Int J Color Dis"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"102521","DOI":"10.1016\/j.ctim.2020.102521","article-title":"Electro-acupuncture vs. sham electro-acupuncture for chronic severe functional constipation: a systematic review and meta-analysis","volume":"54","author":"Zhang","year":"2020","journal-title":"Complement Ther Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1007\/s11655-020-3269-2","article-title":"Role of parameter setting in electroacupuncture: current scenario and future prospects","author":"Zhang","year":"2022","journal-title":"Chin J Integr Med"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1002\/ar.24871","article-title":"Acupuncture for gastrointestinal diseases","author":"Li","year":"2023","journal-title":"Anatomical Rec"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1111\/ner.13099","article-title":"Electro-neuromodulation for colonic disorders-review of meta-analyses, systematic reviews, and RCTs","author":"Southwell","year":"2020","journal-title":"Neuromodulation"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"732","DOI":"10.19852\/j.cnki.jtcm.20220719.001","article-title":"Electroacupuncture at Tianshu (ST25) and Zusanli (ST36) alleviates stress-induced irritable bowel syndrome in mice by modulating gut microbiota and corticotropin-releasing factor","volume":"42","author":"Mengzhu","year":"2022","journal-title":"J Tradit Chin Med"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1097\/MCG.0000000000001645","article-title":"Efficacy of Electroacupuncture compared with transcutaneous electrical stimulation for severe chronic constipation: a randomized controlled pilot trial","author":"Zeng","year":"2022","journal-title":"J Clin Gastroenterol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"397","DOI":"10.19852\/j.cnki.jtcm.20230105.002","article-title":"Effects of acupuncture on functional gastrointestinal disorders: special effects, coeffects, synergistic effects in terms of single or compatible acupoints","author":"Jun","year":"2023","journal-title":"J Traditi Chinese Med"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1186\/s12906-016-1377-5","article-title":"Electroacupuncture at acupoint ST 37(Shangjuxu) improves function of the enteric nervous system in a novel mouse constipation model","author":"Liang","year":"2016","journal-title":"BMC Complement Altern Med"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"293","DOI":"10.13702\/j.1000-0607.190743","article-title":"Effect of electroacupuncture of \"Hegu\" (LI4) and \"Zusanli\" (ST36) on intestinal sensitivity and motility in irritable bowel syndrome rats","author":"Qin","year":"2020","journal-title":"Zhen Ci Yan Jiu"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"5113473","DOI":"10.1155\/2022\/5113473","article-title":"Effects of Electroacupuncture on gastrointestinal motility function, pain, and inflammation via transient receptor potential Vanilloid 1 in a rat model after colonic anastomoses","author":"Zhong","year":"2022","journal-title":"Dis Markers"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.wjam.2022.12.001","article-title":"The dose-effect relationship of electroacupuncture analgesia and its stimulus parameters: Progress in the last 3 decades","author":"Liang","year":"2022","journal-title":"World J Acupuncture Moxibustion"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1017375","DOI":"10.3389\/fpubh.2022.1017375","article-title":"Transcutaneous electrical acupoint stimulation combined with electroacupuncture promotes rapid recovery after abdominal surgery: study protocol for a randomized controlled trial","author":"Li","year":"2022","journal-title":"Front Public Health"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"477","DOI":"10.13703\/j.0255-2930.2019.05.005","article-title":"Effect of electroacupuncture preconditioning with different frequencies on anal pain after milligan-morgan hemorrhoidectomy","author":"Long","year":"2019","journal-title":"Zhongguo Zhen Jiu"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"710","DOI":"10.13702\/j.1000-0607.20210638","article-title":"Effect of electroacupuncture of \"Tianshu\"(ST25) at different frequencies on electromyography and immunoactivity of SP and VIP of colon in rats with slow transit constipation","author":"Cui","year":"2022","journal-title":"Zhen Ci Yan Jiu"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"114516","DOI":"10.1016\/j.biopha.2023.114516","article-title":"The mechanistic basis for the effects of electroacupuncture on neuropathic pain within the central nervous system","author":"Zhou","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s40001-022-00795-9","article-title":"Research on electroacupuncture parameters for knee osteoarthritis based on data mining","volume":"27","author":"Cai","year":"2022","journal-title":"Eur J Med Res"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.3390\/biomedicines10092153","article-title":"NFkB pathway and Hodgkin lymphoma","author":"Jardin","year":"2022","journal-title":"Biomedicines"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1093\/alcalc\/agw098","article-title":"The role of NFkB in drug addiction: beyond inflammation","author":"Nennig","year":"2017","journal-title":"Alcohol Alcoholism"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.cell.2016.12.012","article-title":"30 years of NF-\u03baB: a blossoming of relevance to human pathobiology","author":"Zhang","year":"2017","journal-title":"Cell"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1749-6632.2012.06523.x","article-title":"TNF-\u03b1-induced intestinal epithelial cell shedding: implications for intestinal barrier function","author":"Watson","year":"2012","journal-title":"Ann N Y Acad Sci"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.3389\/fimmu.2020.01455","article-title":"Toll-like receptor 4 (TLR4)\/opioid receptor pathway crosstalk and impact on opioid analgesia, immune function, and gastrointestinal motility","author":"Zhang","year":"2020","journal-title":"Front Immunol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1044662","DOI":"10.3389\/fimmu.2022.1044662","article-title":"MyD88-dependent signaling drives toll-like receptor-induced trained immunity in macrophages","author":"Owen","year":"2022","journal-title":"Front Immunol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"3834","DOI":"10.3390\/cells11233834","article-title":"Delivery of active AKT1 to human cells","author":"Siddika","year":"2022","journal-title":"Cells"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"228","DOI":"10.15171\/mejdd.2017.78","article-title":"The association between modulating inflammatory cytokines and constipation of geriatrics in Iran","author":"Mokhtare","year":"2017","journal-title":"Middle East J Dig Dis"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e2004433","DOI":"10.1002\/advs.202004433","article-title":"Cytokines: from clinical significance to quantification","author":"Liu","year":"2021","journal-title":"Adv Sci"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1124\/jpet.113.212522","article-title":"Hypercontractility of intestinal longitudinal smooth muscle induced by cytokines is mediated by the nuclear factor-\u03baB\/AMP-activated kinase\/myosin light chain kinase pathway","author":"Nalli","year":"2014","journal-title":"J Pharmacol Exp Ther"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1080\/15548627.2021.1909406","article-title":"How autophagy controls the intestinal epithelial barrier","author":"Foerster","year":"2022","journal-title":"Autophagy"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"115845","DOI":"10.1016\/j.bcp.2023.115845","article-title":"CDP-choline modulates cholinergic signaling and gut microbiota to alleviate DSS-induced inflammatory bowel disease","volume":"217","author":"Guo","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.1002\/jcp.25307","article-title":"The involvement of parasympathetic and sympathetic nerve in the inflammatory reflex","author":"Pereira","year":"2016","journal-title":"J Cell Physiol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e143770","DOI":"10.1172\/JCI143770","article-title":"Gut-brain communication and obesity: understanding functions of the vagus nerve","author":"Berthoud","year":"2021","journal-title":"J Clin Invest"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1034547","DOI":"10.3389\/fnins.2022.1034547","article-title":"Slow, deep breathing intervention improved symptoms and altered rectal sensitivity in patients with constipation-predominant irritable bowel syndrome","author":"Liu","year":"2022","journal-title":"Front Neurosci"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"G552","DOI":"10.1152\/ajpgi.00264.2021","article-title":"Interstitial cells of Cajal and human colon motility in health and disease","author":"Huizinga","year":"2021","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1540\/jsmr.59.1","article-title":"Interstitial cells of Cajal in gastrointestinal inflammatory diseases","author":"Kaji","year":"2023","journal-title":"J Smooth Muscle Res"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s00018-018-2943-4","article-title":"An insight into gut microbiota and its functionalities","author":"Adak","year":"2019","journal-title":"Cell Mol Life Sci"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.chom.2022.02.004","article-title":"Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis","author":"Cai","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"e21870","DOI":"10.1016\/j.heliyon.2023.e21870","article-title":"Classical famous prescription of Jichuan decoction improved loperamide-induced slow transit constipation in rats through the cAMP\/PKA\/AQPs signaling pathway and maintained inflammatory\/intestinal flora homeostasis","author":"Lin","year":"2023","journal-title":"Heliyon"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"913420","DOI":"10.3389\/fphar.2022.913420","article-title":"Based on network pharmacology and gut microbiota analysis to investigate the mechanism of the laxative effect of pterostilbene on loperamide-induced slow transit constipation in mice","author":"Yao","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/S1470-2045(05)70168-6","article-title":"The MAPK signalling pathways and colorectal cancer","author":"Fang","year":"2005","journal-title":"Lancet Oncol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.3892\/etm.2020.8454","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","author":"Guo","year":"2020","journal-title":"Exp Ther Med"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10753-016-0447-7","article-title":"Indirubin inhibits LPS-induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways","author":"Lai","year":"2017","journal-title":"Inflammation"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1482066\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T18:23:46Z","timestamp":1733941426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1482066\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,11]]},"references-count":52,"alternative-id":["10.3389\/fmed.2024.1482066"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2024.1482066","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,11]]},"article-number":"1482066"}}