{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:40:52Z","timestamp":1792471252591,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2022\u2010JYB\u2010XJSJJ037"],"award-info":[{"award-number":["2022\u2010JYB\u2010XJSJJ037"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2025\u2010JYB\u2010JBGS\u2010030"],"award-info":[{"award-number":["2025\u2010JYB\u2010JBGS\u2010030"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chronic prostatitis\/chronic pelvic pain syndrome (CP\/CPPS) is a prevalent pelvic pain disorder in men, yet effective pharmacotherapies remain limited. Emerging evidence suggests that oxidative stress and dysregulated iron metabolism contribute to the pathogenesis of CP\/CPPS, with ferroptosis increasingly implicated in CP\/CPPS\u2010related pathology. Qianlie Zhitong Formula (QLZTF) has shown therapeutic potential in treating CP\/CPPS; however, its underlying mechanisms remain incompletely understood. This study integrated proteomics, metabolomics, and in\u00a0vivo experiments to investigate the therapeutic mechanisms of QLZTF. A carrageenan\u2010induced rat model was established, and rats were randomly assigned to five groups: control, model, Qianliekang, low\u2010dose QLZTF, and high\u2010dose QLZTF. QLZTF significantly reduced inflammatory cytokines (TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2), alleviated pain responses, and ameliorated prostate tissue injury. Proteomic analysis identified BCAT2, ALDH1B1, and ALDH2 as significantly upregulated proteins closely associated with ferroptosis. KEGG enrichment analysis of both proteomic and metabolomic data revealed that pantothenate and CoA biosynthesis and branched\u2010chain amino acid (BCAA) degradation pathways were significantly enriched. Integrated analysis indicated that QLZTF synergistically regulates these pathways, activates the BCAT2\/ALDH axis, and inhibits ferroptosis, thereby alleviating inflammation, pain, and fibrosis in CP\/CPPS. This study provides the first multiomics evidence for the anti\u2010ferroptotic mechanism of QLZTF.<\/jats:p>","DOI":"10.1111\/cbdd.70401","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:32:04Z","timestamp":1792470724000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism of Qianlie Zhitong Formula Against Chronic Prostatitis Based on Proteomics and Metabolomics"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6779-9775","authenticated-orcid":false,"given":"Lidan","family":"Dong","sequence":"first","affiliation":[{"name":"WANG Qi Academy National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6759-2433","authenticated-orcid":false,"given":"Linhan","family":"Chang","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caijia","family":"Song","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantong","family":"Shen","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1364-475X","authenticated-orcid":false,"given":"Zhen","family":"Ding","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8199-6035","authenticated-orcid":false,"given":"Yanfei","family":"Zheng","sequence":"additional","affiliation":[{"name":"WANG Qi Academy National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"WANG Qi Academy National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.3390\/medicina61061110","article-title":"Prevalence of Sexual Dysfunction with Chronic Prostatitis\/Chronic Pelvic Pain Syndrome (CP\/CPPS): An Updated Systematic Review and Meta\u2010Analysis","volume":"61","author":"Alshahrani S.","year":"2025","journal-title":"Medicina"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1093\/nutrit\/nuy037","article-title":"Immunomodulatory role of branched\u2010chain amino acids","volume":"76","author":"Bonvini A.","year":"2018","journal-title":"Nutrition Reviews"},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"3393","DOI":"10.7150\/ijbs.94704","article-title":"P2X7R Modulates NEK7\u2010NLRP3 Interaction to Exacerbate Experimental Autoimmune Prostatitis via GSDMD\u2010mediated Prostate Epithelial Cell Pyroptosis","volume":"20","author":"Chen L.","year":"2024","journal-title":"International Journal of Biological Sciences"},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-022-34096-w","article-title":"A noncanonical function of EIF4E limits ALDH1B1 activity and increases susceptibility to ferroptosis","volume":"13","author":"Chen X.","year":"2022","journal-title":"Nature Communications"},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2023.1104725","article-title":"Lipid droplets and polyunsaturated fatty acid trafficking: Balancing life and death","volume":"11","author":"Danielli M.","year":"2023","journal-title":"Frontiers in Cell and Developmental Biology"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.2147\/NDT.S211288","article-title":"Microglial activation and neurobiological alterations in experimental autoimmune prostatitis\u2010induced depressive\u2010like behavior in mice","volume":"15","author":"Du H.\u2010X.","year":"2019","journal-title":"Neuropsychiatric Disease and Treatment"},{"key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/bju.14988","article-title":"Pharmacological Interventions for Treating Chronic Prostatitis\/Chronic Pelvic Pain Syndrome: A Cochrane Systematic Review","volume":"125","author":"Franco J. A. V.","year":"2020","journal-title":"BJU International"},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.3390\/nu15153411","article-title":"Hydroxysafflor Yellow A Alleviates Acute Myocardial Ischemia\/Reperfusion Injury in Mice by Inhibiting Ferroptosis via the Activation of the HIF\u20101\u03b1\/SLC7A11\/GPX4 Signaling Pathway","volume":"15","author":"Ge C.","year":"2023","journal-title":"Nutrients"},{"key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"5759","DOI":"10.2147\/JIR.S508576","article-title":"IGF1R Promotes Th17\/Treg Cell Development in Experimental Autoimmune Prostatitis","volume":"18","author":"Guan Y.","year":"2025","journal-title":"Journal of Inflammation Research"},{"key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1097\/JU.0000000000004564","article-title":"Male Chronic Pelvic Pain: AUA Guideline: Part I Evaluation and Management Approach","volume":"214","author":"Lai H. H.","year":"2025","journal-title":"Journal of Urology"},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/JU.0000000000004565","article-title":"Male Chronic Pelvic Pain: AUA Guideline: Part II Treatment of Chronic Prostatitis\/Chronic Pelvic Pain Syndrome","volume":"214","author":"Lai H. H.","year":"2025","journal-title":"Journal of Urology"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0314599","article-title":"Lc\u2014ms\u2010based untargeted metabolomics reveals potential mechanisms of histologic chronic inflammation promoting prostate hyperplasia","volume":"19","author":"Li J.","year":"2024","journal-title":"PLoS One"},{"key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/s41419-023-06135-x","article-title":"PPM1K mediates metabolic disorder of branched\u2010chain amino acid and regulates cerebral ischemia\u2010reperfusion injury by activating ferroptosis in neurons","volume":"14","author":"Li T.","year":"2023","journal-title":"Cell Death & Disease"},{"key":"e_1_2_12_15_1","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2024.1390257","article-title":"Saikosaponin A attenuates osteoclastogenesis and bone loss by inducing ferroptosis","volume":"11","author":"Li T.\u2010Q.","year":"2024","journal-title":"Frontiers in Molecular Biosciences"},{"key":"e_1_2_12_16_1","article-title":"Targeting Ferroptosis Attenuates Inflammation, Fibrosis, and Mast Cell Activation in Chronic Prostatitis","volume":"2022","author":"Lin D.","year":"2022","journal-title":"Journal of Immunology Research"},{"key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.32604\/ecn.2026.082885","article-title":"Targeting the cytokine\u2010epigenetic axis: a new paradigm and prospects for disease treatment","volume":"37","author":"Luo Y.","year":"2026","journal-title":"European Cytokine Network"},{"key":"e_1_2_12_18_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2025.114128","article-title":"Study progress of etiologic mechanisms of chronic prostatitis\/chronic pelvic pain syndrome","volume":"148","author":"Ma X.","year":"2025","journal-title":"International Immunopharmacology"},{"key":"e_1_2_12_19_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s13287-021-02269-x","article-title":"Extracellular vesicles released from hiPSC\u2010derived MSCs attenuate chronic prostatitis\/chronic pelvic pain syndrome in rats by immunoregulation","volume":"12","author":"Peng X.","year":"2021","journal-title":"Stem Cell Research & Therapy"},{"key":"e_1_2_12_20_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2022.101457","article-title":"Oral Pharmacological Treatments For Chronic Prostatitis\/Chronic Pelvic Pain Syndrome: A Systematic Review and Network Meta\u2010Analysis of Randomised Controlled Trials","volume":"48","author":"Qin Z.","year":"2022","journal-title":"EClinicalMedicine"},{"key":"e_1_2_12_21_1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.freeradbiomed.2024.08.026","article-title":"Targeting ALDH2 to augment platinum\u2010based chemosensitivity through ferroptosis in lung adenocarcinoma","volume":"224","author":"Shan G.","year":"2024","journal-title":"Free Radical Biology & Medicine"},{"key":"e_1_2_12_22_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2025.120828","article-title":"Therapeutic Mechanism of Qingre Tonglin Capsules (QRTL) in CNP via Inflammasome Suppression","volume":"356","author":"Song W.","year":"2026","journal-title":"Journal of Ethnopharmacology"},{"key":"e_1_2_12_23_1","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1038\/s41418-020-00644-4","article-title":"Branched\u2010chain amino acid aminotransferase 2 regulates ferroptotic cell death in cancer cells","volume":"28","author":"Wang K.","year":"2021","journal-title":"Cell Death and Differentiation"},{"key":"e_1_2_12_24_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2026.121384","article-title":"Saikosaponin D alleviates chronic prostatitis\/chronic pelvic pain syndrome by regulating the NF\u2010\u03baB pathway via lncRNA5682","volume":"363","author":"Wang X.","year":"2026","journal-title":"Journal of Ethnopharmacology"},{"key":"e_1_2_12_25_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-04916-2","article-title":"Naringin Mitigates Experimental Autoimmune Prostatitis by Modulating Oxidative Stress and the NLRP3 Inflammasome via the PPAR\u2010\u03b3\/NF\u2010\u03baB Pathway","volume":"15","author":"Wang Z.","year":"2025","journal-title":"Scientific Reports"},{"key":"e_1_2_12_26_1","first-page":"6608","article-title":"Research Progress on Pharmacological Actions and Clinical Applications of Carthami Flos","volume":"36","author":"Wang Z. M.","year":"2021","journal-title":"China Journal of Traditional Chinese Medicine and Pharmacy"},{"key":"e_1_2_12_27_1","first-page":"30","article-title":"Clinical Observation on Modified Fuyuan Huoxue Decoction in the Treatment of Type III Prostatitis","volume":"20","author":"Wu W. S.","year":"2011","journal-title":"Chinese Journal of Human Sexuality"},{"key":"e_1_2_12_28_1","doi-asserted-by":"crossref","DOI":"10.1002\/inmd.70120","article-title":"SUMOylation regulates tumorigenesis and progression: Molecular mechanisms and therapeutic applications","volume":"4","author":"Wu Y.","year":"2026","journal-title":"Interdisciplinary Medicine"},{"key":"e_1_2_12_29_1","first-page":"397","article-title":"Effect of Fuyuan Huoxue Decoction on Cytokines in Prostatic Fluid of Chronic Nonbacterial Prostatitis","volume":"53","author":"Xie Z. G.","year":"2018","journal-title":"Zhejiang Journal of Traditional Chinese Medicine"},{"key":"e_1_2_12_30_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4103\/aja202434","article-title":"Chronic prostatitis\/chronic pelvic pain syndrome induces metabolomic changes in expressed prostatic secretions and plasma","volume":"27","author":"Zhang F. X.","year":"2025","journal-title":"Asian Journal of Andrology"},{"key":"e_1_2_12_31_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.freeradbiomed.2024.07.015","article-title":"CXCR4 influences PUFA desaturation and oxidative stress injury in experimental prostatitis mice by activating Fads2 via PPAR\u03b3","volume":"223","author":"Zhang Y.","year":"2024","journal-title":"Free Radical Biology & Medicine"},{"key":"e_1_2_12_32_1","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s10020-023-00729-z","article-title":"\u03b2\u2010aminoisobutyrics acid, a metabolite of BCAA, activates the AMPK\/Nrf\u20102 pathway to prevent ferroptosis and ameliorates lung ischemia\u2010reperfusion injury","volume":"29","author":"Zhang Z.","year":"2023","journal-title":"Molecular Medicine"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.70401","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.70401","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.70401","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:32:17Z","timestamp":1792470737000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.70401"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/cbdd.70401"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.70401","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70401"}}