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Buyang Huanwu Decoction (BHD) contains PF\u2010improving compounds; it was separated into supernatant (SN) and precipitation component (PC) via water extraction and ethanol precipitation method to explore their differential PF effects, mechanisms, and screen the most effective fraction. Ultra\u2010high\u2010performance liquid chromatography\u2010mass spectrometry and network pharmacology identified BHD compounds and predicted PF targets. Twelve rats (Control, BHD, PC, and SN groups) were used to detect amygdalin, formononetin, kaempferol, ferulic acid, and paeoniflorin in drug\u2010containing serum. A rat PF model was established via intratracheal bleomycin (BLM) instillation. Seventy\u2010two rats were divided into six groups: Control, BLM, BHD, prednisone acetate, SN, and PC. After 21\u2010day treatment, Hematoxylin and Eosin\/Masson staining, alkaline hydrolysis (Hydroxyproline), enzyme\u2010linked immunosorbent assay (tumor necrosis factor\u2010\u03b1\/interleukin\u20106), immunofluorescence (alpha\u2010smooth muscle actin), reverse transcription\u2010quantitative polymerase chain reaction, and Western Blotting (Wnt\/\u03b2\u2010catenin and TGF\u2010\u03b21\/Smad pathways) were used. The SN group exhibited higher serum levels of amygdalin, formononetin, and ferulic acid than the BHD and PC groups, with kaempferol similar to the BHD group. BHD, PC, and SN alleviated BLM\u2010induced lung inflammation and collagen deposition, reduced Wnt3a, glycogen synthase kinase 3 beta, \u03b2\u2010catenin, and transforming growth factor beta 1 (TGF\u2010\u03b21) mRNA\/protein expression, and decreased the p\u2010Smad3\/Smad3 ratio. BHD and its fractions alleviate PF through dual inhibition of Wnt\/\u03b2\u2010catenin and TGF\u2010\u03b21\/Smad pathways, with SN demonstrating the highest overall efficacy.<\/jats:p>","DOI":"10.1002\/cbdv.202503027","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:16:57Z","timestamp":1770884217000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Buyang Huanwu Decoction Alleviates Bleomycin\u2010Induced Pulmonary Fibrosis via Wnt\/\u03b2\u2010catenin and TGF\u2010\u03b21\/Smad Pathways"],"prefix":"10.1002","volume":"23","author":[{"given":"Yunyue","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Heilongjiang University of Chinese Medicine  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingtong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Heilongjiang University of Chinese Medicine  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinbiao","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Heilongjiang University of Chinese Medicine  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Xue","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Heilongjiang University of Chinese Medicine  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Heilongjiang University of Chinese Medicine  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbin","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Heilongjiang University of Chinese Medicine  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Heilongjiang University of Chinese Medicine  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6105-9266","authenticated-orcid":false,"given":"Wenying","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Heilongjiang University of Chinese Medicine  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"issue":"10","key":"e_1_2_12_2_1","first-page":"1054","article-title":"Advances in the Pathogenesis of Idiopathic Pulmonary Fibrosis","volume":"59","author":"Huang Y.","year":"2024","journal-title":"Chinese Journal of 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