{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T04:05:41Z","timestamp":1779509141586,"version":"3.53.1"},"reference-count":46,"publisher":"International Research and Cooperation Association for Bio & Socio-Sciences Advancement (IRCA-BSSA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["DD&amp;T"],"published-print":{"date-parts":[[2026,4,30]]},"DOI":"10.5582\/ddt.2026.01009","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T22:09:10Z","timestamp":1776204550000},"page":"128-146","source":"Crossref","is-referenced-by-count":0,"title":["Amelioration of gastrointestinal motility and gut dysbiosis by acupoint application of Tongfu Powder to loperamide-induced constipation in mice"],"prefix":"10.5582","volume":"20","author":[{"given":"Ke","family":"Wang","sequence":"first","affiliation":[{"name":"Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Ji&apos;nan, China."},{"name":"Xuzhou Tongshan District Hospital of Traditional Chinese Medicine, Xu&apos;zhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Cai","sequence":"additional","affiliation":[{"name":"Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Ji&apos;nan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Ji&apos;nan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixue","family":"Wang","sequence":"additional","affiliation":[{"name":"Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Ji&apos;nan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Ji&apos;nan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanghua","family":"Qi","sequence":"additional","affiliation":[{"name":"Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Ji&apos;nan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3542","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Aziz I, Whitehead WE, Palsson OS, T\u00f6rnblom H, Simr\u00e9n M. An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation. Expert Rev Gastroenterol Hepatol. 2020; 14:39-46.","DOI":"10.1080\/17474124.2020.1708718"},{"key":"2","unstructured":"2. Ihara E, Manabe N, Ohkubo H, <i>et al<\/i>. Evidence-Based Clinical Guidelines for Chronic Constipation 2023. Digestion. 2025; 106:62-89."},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Barbara G, Barbaro MR, Marasco G, Cremon C. Chronic constipation: from pathophysiology to management. Minerva Gastroenterol (Torino). 2023; 69:277-290.","DOI":"10.23736\/S2724-5985.22.03335-6"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Harris LA, Chang CH. Burden of Constipation: Looking Beyond Bowel Movements. Am J Gastroenterol. 2022; 117:S2-S5.","DOI":"10.14309\/ajg.0000000000001708"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Chang L, Chey WD, Imdad A, Almario CV, Bharucha AE, Diem S, Greer KB, Hanson B, Harris LA, Ko C, Murad MH, Patel A, Shah ED, Lembo AJ, Sultan S. American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation. Gastroenterology. 2023; 164:1086-1106.","DOI":"10.1053\/j.gastro.2023.03.214"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Shah ED, Staller K, Nee J, Ahuja NK, Chan WW, Lembo A, Brenner DM, Siegel CA, Chey WD. Evaluating the Impact of Cost on the Treatment Algorithm for Chronic Idiopathic Constipation: Cost-Effectiveness Analysis. Am J Gastroenterol. 2021; 116:2118-2127.","DOI":"10.14309\/ajg.0000000000001403"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Tan S, Peng C, Lin X, Peng C, Yang Y, Liu S, Huang L, Bian Y, Li Y, Xu C. Clinical efficacy of non-pharmacological treatment of functional constipation: a systematic review and network meta-analysis. Front Cell Infect Microbiol. 2025; 15:1565801.","DOI":"10.3389\/fcimb.2025.1680092"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Cui J, Wang J, Wang Y, Zhang C, Hu G, Wang Z. External treatment of traditional Chinese medicine for functional dyspepsia in children: Protocol for a systematic review and network meta-analysis. Medicine (Baltimore). 2022; 101:e31597.","DOI":"10.1097\/MD.0000000000031597"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Wang K, Qiu H, Chen F, Cai P, Qi F. Considering traditional Chinese medicine as adjunct therapy in the management of chronic constipation by regulating intestinal flora. Biosci Trends. 2024; 18:127-140.","DOI":"10.5582\/bst.2024.01036"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Wang Q, Zhao L, Liu J, Chen L, Zhang B, Zhang Q, Lu Y, Gao Y, Zheng X, He Z, Jing S. Meta analysis of clinical efficacy of acupoint application in the treatment of irritable bowel syndrome. Afr Health Sci. 2024; 24:351-361.","DOI":"10.4314\/ahs.v24i4.44"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Gao H, He C, Xin S, Hua R, Du Y, Wang B, Gong F, Yu X, Pan L, Liang C, Gao L, Shang H, Xu JD. Rhubarb extract rebuilding the mucus homeostasis and regulating mucin-associated flora to relieve constipation. Exp Biol Med (Maywood). 2023; 248:2449-2463.","DOI":"10.1177\/15353702231211859"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Wang L, Wu F, Hong Y, Shen L, Zhao L, Lin X. Research progress in the treatment of slow transit constipation by traditional Chinese medicine. J Ethnopharmacol. 2022; 290:115075.","DOI":"10.1016\/j.jep.2022.115075"},{"key":"13","unstructured":"13. Tian H, Huang D, Li T, Huang L, Zheng X, Tang D, Zhang L, Wang J. The protective effects of total phenols in magnolia officinalix rehd. et wils on gastrointestinal tract dysmotility is mainly based on its influence on interstitial cells of cajal. Int J Clin Exp Med. 2015; 8:20279-20286."},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Li CB, Yang X, Tang WB, Liu CY, Xie DP. Arecoline excites the contraction of distal colonic smooth muscle strips in rats <i>via<\/i> the M3 receptor-extracellular Ca<sup>2+<\/sup> influx- Ca<sup>2+<\/sup> store release pathway. Can J Physiol Pharmacol. 2010; 88:439-447.","DOI":"10.1139\/Y10-024"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Xu M, Wang W, Su S, Li W, Hu X, Zhang J. Arecoline alleviated loperamide induced constipation by regulating gut microbes and the expression of colonic genome. Ecotoxicol Environ Saf. 2023; 264:115423.","DOI":"10.1016\/j.ecoenv.2023.115423"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Kulkarni M, Sawant N, Kolapkar A, Huprikar A, Desai N. Borneol: a Promising Monoterpenoid in Enhancing Drug Delivery Across Various Physiological Barriers. AAPS PharmSciTech. 2021; 22:145.","DOI":"10.1208\/s12249-021-01999-8"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Zheng H, Chen Y, Lu S, Liu Z, Ma Y, Zhang C, Zhang Y, Zhang J, Liu C, Chu M, Pei F, Liu S, Duan L. Mechanosensory Piezo2 regulated by gut microbiota participates in the development of visceral hypersensitivity and intestinal dysmotility. Gut Microbes. 2025; 17:2497399.","DOI":"10.1080\/19490976.2025.2497399"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Xu X, Wang Y, Long Y, Cheng Y. Chronic constipation and gut microbiota: current research insights and therapeutic implications. Postgrad Med J. 2024; 100:890-897.","DOI":"10.1093\/postmj\/qgae112"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Yuan F, Lu F, Guo Y, Zhang C. Acupoint Application Combined with Acupoint Massage for Treating Constipation in a Patient with Chronic Obstructive Pulmonary Disease. J Vis Exp. 2023; 198.","DOI":"10.3791\/64900"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Kojima R, Doihara H, Nozawa K, Kawabata-Shoda E, Yokoyama T, Ito H. Characterization of two models of drug-induced constipation in mice and evaluation of mustard oil in these models. Pharmacology. 2009; 84:227-233.","DOI":"10.1159\/000236524"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Qi FH, Cai PP, Liu X, Si GM. Adenovirus-mediated P311 ameliorates renal fibrosis through inhibition of epithelial-mesenchymal transition <i>via<\/i> TGF-\u03b21-Smad-ILK pathway in unilateral ureteral obstruction rats. Int J Mol Med. 2018; 41:3015-3023.","DOI":"10.3892\/ijmm.2018.3485"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Zhao L, Cheng N, Sun B, Wang S, Li A, Wang Z, Wang Y, Qi F. Regulatory effects of Ningdong granule on microglia-mediated neuroinflammation in a rat model of Tourette&apos;s syndrome. Biosci Trends. 2020; 14:271-278.","DOI":"10.5582\/bst.2020.03262"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Qi F, Wang J, Zhao L, Cai P, Tang W, Wang Z. Cinobufacini inhibits epithelial-mesenchymal transition of human hepatocellular carcinoma cells through c-Met\/ERK signaling pathway. Biosci Trends. 2018; 12:291-297.","DOI":"10.5582\/bst.2018.01082"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Ma YN, Jiang XM, Hu XQ, Wang L, Gao JJ, Liu H, Qi FH, Song PP, Tang W. Cinobufacini Inhibits Survival and Metastasis of Hepatocellular Carcinoma <i>via<\/i> c-Met Signaling Pathway. Chin J Integr Med. 2025; 31:311-325.","DOI":"10.1007\/s11655-024-4111-z"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Chai Y, Huang Y, Tang H, Tu X, He J, Wang T, Zhang Q, Xiong F, Li D, Qiu Z. Role of stem cell growth factor\/c-Kit in the pathogenesis of irritable bowel syndrome. Exp Ther Med. 2017; 13:1187-1193.","DOI":"10.3892\/etm.2017.4133"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Chen CM, Wu CC, Huang CL, Chang MY, Cheng SH, Lin CT, Tsai YC. Lactobacillus plantarum PS128 Promotes Intestinal Motility, Mucin Production, and Serotonin Signaling in Mice. Probiotics Antimicrob Proteins. 2022; 14:535-545.","DOI":"10.1007\/s12602-021-09814-3"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27. Wei L, Luo Y, Zhang X, Liu Y, Gasser M, Tang F, Ouyang WW, Wei H, Lu S, Yang Z, Waaga-Gasser AM, Deng C, Lin M. Topical therapy with rhubarb navel plasters in patients with chronic constipation: Results from a prospective randomized multicenter study. J Ethnopharmacol. 2021; 264:113096.","DOI":"10.1016\/j.jep.2020.113096"},{"key":"28","unstructured":"28. Yan L, Liu H, Yan R, Tan L, Tan J, Lei Y. Effect of traditional Chinese medicine external therapy for functional constipation: a meta-analysis. Am J Transl Res. 2023; 15:13-26."},{"key":"29","doi-asserted-by":"crossref","unstructured":"29. Koh SD, Drumm BT, Lu H, Kim HJ, Ryoo SB, Kim HU, Lee JY, Rhee PL, Wang Q, Gould TW, Heredia D, Perrino BA, Hwang SJ, Ward SM, Sanders KM. Propulsive colonic contractions are mediated by inhibition-driven poststimulus responses that originate in interstitial cells of Cajal. Proc Natl Acad Sci U S A. 2022; 119:e2123020119.","DOI":"10.1073\/pnas.2123020119"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30. Tang X, Huang Y, Jiang T, Wu J, Wang K, Wu W. Pathophysiological mechanisms, diagnostic innovations, and multimodal therapeutic strategies for slow transit constipation. BMC Gastroenterol. 2025; 25:810.","DOI":"10.1186\/s12876-025-04387-9"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31. Yin J, Liang Y, Wang D, Yan Z, Yin H, Wu D, Su Q. Naringenin induces laxative effects by upregulating the expression levels of c-Kit and SCF, as well as those of aquaporin 3 in mice with loperamide-induced constipation. Int J Mol Med. 2018; 41:649-658.","DOI":"10.3892\/ijmm.2017.3301"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32. Wei L, Singh R, Ha SE, Martin AM, Jones LA, Jin B, Jorgensen BG, Zogg H, Chervo T, Gottfried-Blackmore A, Nguyen L, Habtezion A, Spencer NJ, Keating DJ, Sanders KM, Ro S. Serotonin Deficiency Is Associated With Delayed Gastric Emptying. Gastroenterology. 2021; 160:2451-2466.e19.","DOI":"10.1053\/j.gastro.2021.02.060"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33. Hoffman JM, Tyler K, MacEachern SJ, Balemba OB, Johnson AC, Brooks EM, Zhao H, Swain GM, Moses PL, Galligan JJ, Sharkey KA, Greenwood-Van Meerveld B, Mawe GM. Activation of colonic mucosal 5-HT(4) receptors accelerates propulsive motility and inhibits visceral hypersensitivity. Gastroenterology. 2012; 142:844-854.e4.","DOI":"10.1053\/j.gastro.2011.12.041"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34. Yan X, Ma P, Wang W, Zeng W, Li Y, Hou Y, Ye J, Zheng Q, Zhang W, Yao J, Li Y. Piezo knockdown reduces 5\u2011hydroxytryptamine release from enterochromaffin cells and exacerbates intestinal dyskinesia in mice with functional constipation. Int J Mol Med. 2025; 56:178.","DOI":"10.3892\/ijmm.2025.5619"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35. Cao H, Liu X, An Y, Zhou G, Liu Y, Xu M, Dong W, Wang S, Yan F, Jiang K, Wang B. Dysbiosis contributes to chronic constipation development <i>via<\/i> regulation of serotonin transporter in the intestine. Sci Rep. 2017; 7:10322.","DOI":"10.1038\/s41598-017-10835-8"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36. Liu Y, Yu Z, Zhu L, Ma S, Luo Y, Liang H, Liu Q, Chen J, Guli S, Chen X. Orchestration of MUC2 - The key regulatory target of gut barrier and homeostasis: A review. Int J Biol Macromol. 2023; 236:123862.","DOI":"10.1016\/j.ijbiomac.2023.123862"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37. Horowitz A, Chanez-Paredes SD, Haest X, Turner JR. Paracellular permeability and tight junction regulation in gut health and disease. Nat Rev Gastroenterol Hepatol. 2023; 20:417-432.","DOI":"10.1038\/s41575-023-00766-3"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38. Zhang S, Wang R, Li D, Zhao L, Zhu L. Role of gut microbiota in functional constipation. Gastroenterol Rep (Oxf). 2021; 9:392-401.","DOI":"10.1093\/gastro\/goab035"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39. Liu SH, Yang XF, Liang L, Song BB, Song XM, Yang YJ, Alhoot MA. Regulatory mechanisms of the gut microbiota-short chain fatty acids signaling axis in slow transit constipation and progress in multi-target interventions. Front Microbiol. 2025; 16:1689597.","DOI":"10.3389\/fmicb.2025.1689597"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40. Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, Pudlo NA, Kitamoto S, Terrapon N, Muller A, Young VB, Henrissat B, Wilmes P, Stappenbeck TS, N\u00fa\u00f1ez G, Martens EC. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell. 2016; 167:1339-1353.e21.","DOI":"10.1016\/j.cell.2016.10.043"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41. Tan R, Dong H, Chen Z, Jin M, Yin J, Li H, Shi D, Shao Y, Wang H, Chen T, Yang D, Li J. Intestinal Microbiota Mediates High-Fructose and High-Fat Diets to Induce Chronic Intestinal Inflammation. Front Cell Infect Microbiol. 2021; 11:654074.","DOI":"10.3389\/fcimb.2021.654074"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42. Wang L, Chai M, Wang J, Yu Q, Wang G, Zhang H, Zhao J, Chen W. Bifidobacterium longum relieves constipation by regulating the intestinal barrier of mice. Food Funct. 2022; 13:5037-5049.","DOI":"10.1039\/D1FO04151G"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43. Wei Y, Huang N, Ye X, Liu M, Wei M, Huang Y. The postbiotic of hawthorn-probiotic ameliorating constipation caused by loperamide in elderly mice by regulating intestinal microecology. Front Nutr. 2023; 10:1103463.","DOI":"10.3389\/fnut.2023.1103463"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44. Grander C, Adolph TE, Wieser V, <i>et al<\/i>. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut. 2018; 67:891-901.","DOI":"10.1136\/gutjnl-2016-313432"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45. Jiang JG, Luo Q, Li SS, Tan TY, Xiong K, Yang T, Xiao TB. Cinnamic acid regulates the intestinal microbiome and short-chain fatty acids to treat slow transit constipation. World J Gastrointest Pharmacol Ther. 2023; 14:4-21.","DOI":"10.4292\/wjgpt.v14.i2.4"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46. Forster SC, Liu J, Kumar N, Gulliver EL, Gould JA, Escobar-Zepeda A, Mkandawire T, Pike LJ, Shao Y, Stares MD, Browne HP, Neville BA, Lawley TD. Strain-level characterization of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome. Nat Commun. 2022; 13:1445.","DOI":"10.1038\/s41467-022-29096-9"}],"container-title":["Drug Discoveries &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/ddt\/20\/2\/20_2026.01009\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T03:28:11Z","timestamp":1779506891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/ddt\/20\/2\/20_2026.01009\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.5582\/ddt.2026.01009","relation":{},"ISSN":["1881-7831","1881-784X"],"issn-type":[{"value":"1881-7831","type":"print"},{"value":"1881-784X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"article-number":"2026.01009"}}