{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T11:30:23Z","timestamp":1774956623983,"version":"3.50.1"},"reference-count":68,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008871","name":"Yunnan Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["202101AZ070001\u2010209."],"award-info":[{"award-number":["202101AZ070001\u2010209."]}],"id":[{"id":"10.13039\/501100008871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>This study investigated the impacts and mechanisms of yunweiling in the management of Functional Constipation (FC) using network pharmacology and experimental research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Genecard, and Online Mendelian Inheritance in Man (OMIM) databases, a potential gene target for yunweiling in treating FC was found. A pharmacological network was built and viewed in Cytoscape. A protein interaction map was created with STRING and Cytoscape. \u2018clusterProfiler\u2019 helped uncover its mechanism. Molecular docking was done with AutoDock Vina. In a constipation mouse model, Western blot was used to assess yunweiling's effectiveness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>To investigate yunweiling's therapeutic effects on FC, we employed a loperamide\u2010induced constipation model. Successful model establishment was confirmed by first black stool time, reduced stool output, and impaired gastrointestinal motility. Yunweiling treatment, especially at high and medium doses, significantly alleviated constipation symptoms by reducing first black stool time, increasing stool output, and enhancing gastrointestinal motility. HE staining revealed yunweiling's ability to restore colon tissue structure. Yunweiling modulated the expression of key proteins TP53, P\u2010AKT, P\u2010PI3K, RET, and Rai, implicating its involvement in the PI3K\u2010Akt signaling pathway. Comparative analysis showed yunweiling to be more effective than its individual components (shionone, \u03b2\u2010sitosterol, and daucosterol) in improving constipation. The combination of yunweiling with TP53 and PI3K\u2010Akt inhibitors further enhanced its therapeutic effects, suggesting a synergistic mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The integration of network pharmacology and experimental investigations indicated the effectiveness of yunweiling in managing FC, offering essential theoretical support for clinical application.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12567","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T02:50:34Z","timestamp":1739242234000},"page":"1277-1291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Yunweiling alleviates functional constipation: integrating network pharmacology and experimental study"],"prefix":"10.1002","volume":"8","author":[{"given":"Peng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of General Surgery The First People's Hospital of Yunnan Province  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Spleen and Stomach of Traditional Chinese Medicine Yunnan Provincial Hospital of Chinese Medicine  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Spleen and Stomach of Traditional Chinese Medicine Yunnan Provincial Hospital of Chinese Medicine  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Spleen and Stomach of Traditional Chinese Medicine Yunnan Provincial Hospital of Chinese Medicine  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuonan","family":"She","sequence":"additional","affiliation":[{"name":"Department of Spleen and Stomach of Traditional Chinese Medicine Yunnan Provincial Hospital of Chinese Medicine  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9626-2352","authenticated-orcid":false,"given":"Xia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Spleen and Stomach of Traditional Chinese Medicine Yunnan Provincial Hospital of Chinese Medicine  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weibo","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Yunnan Provincial Hospital of Chinese Medicine  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2020.1708718"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-8-5"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12628"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0578-1426.2017.08.005"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(21)00111-4"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-020-01305-z"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-011-1801-0"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-017-2972-2"},{"issue":"3","key":"e_1_2_12_10_1","first-page":"151","article-title":"Advance of microecological treatment in chronic functional constipation","volume":"30","author":"Huang LS","year":"2017","journal-title":"Infect Dis Info"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/NOR.0000000000000657"},{"issue":"24","key":"e_1_2_12_12_1","first-page":"3016","article-title":"Advances in the diagnosis and treatment of functional constipation","volume":"22","author":"Wang DD","year":"2019","journal-title":"Chin Gen Pract"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.51821\/84.3.012"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10151-019-02011-z"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000001645"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.700718"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12485"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.13935\/j.cnki.sjzx.210508"},{"key":"e_1_2_12_19_1","first-page":"151","volume-title":"Herbal Medicines of Southern Yunnan","author":"Lan M","year":"2009"},{"issue":"4","key":"e_1_2_12_20_1","first-page":"621","article-title":"Effect of Eriobotrya japonica flower flavonides extract on intestinal motility disorders in mice","volume":"58","author":"Jiang F","year":"2019","journal-title":"J Xiamen Univ Nat Sci"},{"key":"e_1_2_12_21_1","first-page":"133","volume-title":"Conference Materials of the 14th Annual Conference of the Basic Theories of Integrated Chinese and Western Medicine, Tianjin, China","author":"Lv DY","year":"2018"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/mp\/ssq070"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-6-13"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25092002"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2010.12.004"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.137"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3930"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2013.1465"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.15171\/mejdd.2017.78"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1fo04151g"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0514-y"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.19540\/j.cnki.cjcmm.20200221.304"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.11.013"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1460"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00423"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i48.9231"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20040946"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.19540\/j.cnki.cjcmm.20200207.302"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.19540\/j.cnki.cjcmm.20201117.406"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.14020"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30697"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1162-y"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14418"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0574-9"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13453"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14309"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.796743"},{"issue":"4","key":"e_1_2_12_51_1","first-page":"1821","article-title":"Shionone suppresses the growth, migration and invasion of human breast cancer cells via induction of apoptosis and inhibition of MEK\/ERK and STAT3 signalling pathways","volume":"25","author":"Xu N","year":"2020","journal-title":"J BUON"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e04023"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.04.051"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-023-03967-8"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.11.042"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173056"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2017.3850"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03470"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106092"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.01.017"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-019-09932-9"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.13422\/j.cnki.syfjx.20221325"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566524021666210618124220"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.13288\/j.11-2166\/r.2018.12.014"},{"key":"e_1_2_12_65_1","volume-title":"Research on GDNF\u2010PI3K\u2010AKT Signal Pathway in FC Mice with Acupuncture Back\u2010Shu and Front\u2010Mu Points Improving Gastrointestinal Transmitting Function","author":"Zhang W","year":"2016"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.13194\/j.issn.1673-842x.2019.11.013"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.946668"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59798-3"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/0162-3109(90)90037-f"}],"container-title":["Animal Models and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.12567","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T20:07:52Z","timestamp":1757707672000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ame2.12567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,10]]},"references-count":68,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/ame2.12567"],"URL":"https:\/\/doi.org\/10.1002\/ame2.12567","archive":["Portico"],"relation":{},"ISSN":["2576-2095","2576-2095"],"issn-type":[{"value":"2576-2095","type":"print"},{"value":"2576-2095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,10]]},"assertion":[{"value":"2024-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}