{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T19:05:10Z","timestamp":1788548710584,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Lab Projects of Xinjiang Key Laboratory of Hotan Characteristic Chinese Traditional Medicine Research","award":["2025HCTMR06Z"],"award-info":[{"award-number":["2025HCTMR06Z"]}]},{"name":"Open Lab Projects of Xinjiang Key Laboratory of Hotan Characteristic Chinese Traditional Medicine Research","award":["2025HCTMR11Y"],"award-info":[{"award-number":["2025HCTMR11Y"]}]},{"name":"Research and Development Plan Project of Hetian District, China","award":["202425"],"award-info":[{"award-number":["202425"]}]},{"name":"Research and Development Plan Project of Hetian District, China","award":["202210"],"award-info":[{"award-number":["202210"]}]},{"DOI":"10.13039\/100009110","name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","doi-asserted-by":"publisher","award":["2025D01C346"],"award-info":[{"award-number":["2025D01C346"]}],"id":[{"id":"10.13039\/100009110","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tianshan Talents Project of Xinjiang Uygur Autonomous Region","award":["2023TSYCJC0048"],"award-info":[{"award-number":["2023TSYCJC0048"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Chronic nonbacterial prostatitis (CNP), the major subset of chronic prostatitis\/chronic pelvic pain syndrome (CP\/CPPS), imposes a substantial global burden yet lacks satisfactory therapies. Maizibizi Wan (MZBZ) has long been used clinically for prostatitis, but its pharmacodynamic substance basis and mechanisms remain unclear. Methods: Ultra-high-performance liquid chromatography\u2013Q-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) coupled with Global Natural Products Social Molecular Networking (GNPS) molecular networking profiled MZBZ constituents and rat plasma\u2013exposed prototype components and metabolites was used. Based on blood-absorbable components, network pharmacology predicted core targets\/pathways; representative interactions were validated by molecular docking. A \u03bb-carrageenan\u2013induced CNBP rat model underwent histopathology (H&amp;E), serum cytokine assays (TNF-\u03b1, IL-1\u03b2, IL-6\/IL-17), immunohistochemistry (COX-2, TNF-\u03b1, MMP-9), and Western blotting (P-p65\/p65, p-AKT\/AKT, COX-2, TGF-\u03b21, BCL2). Results: A total of 188 chemical constituents were identified in MZBZ (79 flavonoids, 38 organic acids, 30 alkaloids, 15 phenylpropanoids, 7 steroids, 4 phenylethanoid glycosides, 15 others). A total of 35 blood-absorbable components (18 prototype components, 17 metabolites) were identified, mainly involving Phase I oxidation and Phase II glucuronidation\/sulfation. Network analysis yielded 54 core targets enriched in NF-\u03baB and PI3K\/AKT signaling and apoptosis. Docking indicated stable binding of key flavonoids to COX-2, NFKB1, TNF, IL-6, and BCL2. In vivo, MZBZ ameliorated prostatic inflammation, reduced serum TNF-\u03b1\/IL-1\u03b2\/IL-6\/IL-17 (p &lt; 0.05 or p &lt; 0.01); decreased P-p65\/p65, p-AKT\/AKT, COX-2, and TGF-\u03b21; and increased BCL2 in prostate tissue. Conclusions: MZBZ exerts anti-CNBP effects via multi-component synergy (prototypes + metabolites) that suppresses inflammatory cytokines, modulates apoptosis, and inhibits NF-\u03baB and PI3K\/AKT pathways. These findings provide a mechanistic basis and quality control cues for the rational clinical use of MZBZ.<\/jats:p>","DOI":"10.3390\/ph19010153","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:13:21Z","timestamp":1768475601000},"page":"153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["UHPLC\u2013Q\u2013Orbitrap\u2013HRMS-Based Multilayer Mapping of the Pharmacodynamic Substance Basis and Mechanistic Landscape of Maizibizi Wan in Chronic Nonbacterial Prostatitis Therapy"],"prefix":"10.3390","volume":"19","author":[{"given":"Maimaitiming","family":"Maihemuti","sequence":"first","affiliation":[{"name":"Xinjiang Key Laboratory of Hetian Characteristic Chinese Traditional Medicine Research, Xinjiang Hetian College, Hetian 848000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muaitaer","family":"Nuermaimaiti","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Hetian Characteristic Chinese Traditional Medicine Research, Xinjiang Hetian College, Hetian 848000, China"},{"name":"School of Pharmacy, Xinjiang Hetian College, Hetian 848000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuermaitihan","family":"Maimaitiming","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Hetian Characteristic Chinese Traditional Medicine Research, Xinjiang Hetian College, Hetian 848000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alimujiang","family":"Paierhati","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Hetian Characteristic Chinese Traditional Medicine Research, Xinjiang Hetian College, Hetian 848000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Ji","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Hetian Characteristic Chinese Traditional Medicine Research, Xinjiang Hetian College, Hetian 848000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammatjan","family":"Abduwaki","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Hetian Characteristic Chinese Traditional Medicine Research, Xinjiang Hetian College, Hetian 848000, China"},{"name":"School of Pharmacy, Xinjiang Hetian College, Hetian 848000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1697-2923","authenticated-orcid":false,"given":"Xinzhou","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, South-Central University for Nationalities, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6155-5103","authenticated-orcid":false,"given":"Nabijan","family":"Mohammadtursun","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Hetian Characteristic Chinese Traditional Medicine Research, Xinjiang Hetian College, Hetian 848000, China"},{"name":"School of Pharmacy, Xinjiang Hetian College, Hetian 848000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.eururo.2015.08.061","article-title":"Contemporary Management of Chronic Prostatitis\/Chronic Pelvic Pain Syndrome","volume":"69","author":"Magistro","year":"2016","journal-title":"Eur. 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