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Subsequent mechanistic investigations were conducted through comparative analyses in peroxisome proliferator-activated receptor \u03b1 gene knockout (\n                      <jats:italic>Ppar\u03b1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice subjected to DDC challenge.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FZHY significantly ameliorated chronic cholestatic liver injury phenotypes in DDC-induced mice, as evidenced by bile acids (BAs) accumulation, inflammation, ductular reaction and biliary fibrosis was remarkably reduced after treatment with FZHY. Transcriptome sequencing analysis revealed that the effect of FZHY on chronic cholestatic liver injury was closely associated with activating PPAR signaling pathway and suppressing nuclear factor kappa-B (NF-\u03baB) signaling. Further research found FZHY did not only enhance the total hepatic content of PPAR\u03b1 protein, but also increased its nuclear to cytoplasmic ratio that was reduced by DDC inducing. Additionally, FZHY suppressed hepatic phosphorylation of I\u03baB\u03b1 and NF-\u03baB. The therapeutic effect of FZHY in treating DDC-induced mice with chronic cholestatic liver injury is similar to that of fenofibrate, a PPAR\u03b1 agonist. Crucially, genetic ablation of\n                      <jats:italic>Ppar\u03b1<\/jats:italic>\n                      substantially abrogated the hepatoprotective and anti-fibrotic effects of FZHY in DDC-induced mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present study underscores FZHY regulated BAs metabolism and alleviated hepatic inflammation and fibrosis by upregulating PPARa in DDC-induced mice. Our study provides novel insights that FZHY might be a promising drug for chronic cholestatic liver injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13020-026-01368-2","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T04:48:08Z","timestamp":1773809288000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fuzheng Huayu formula ameliorates chronic cholestatic liver injury by upregulating PPARa in mice"],"prefix":"10.1186","volume":"21","author":[{"given":"Zheng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En-qi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi-bi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-xin","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao-feng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-ping","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"1368_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12050792","author":"SO Aseem","year":"2023","unstructured":"Aseem SO, Hylemon PB, Zhou H. 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