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Molecular docking was first performed to examine BRB interactions with phosphoinositide 3-kinase (PI3K), a key regulator of cellular survival and autophagy pathways. Hepatotoxicity was induced using diethylnitrosamine (DEN) and carbon tetrachloride (CCl\u2084), resulting in significantly elevated serum uric acid levels (1.35\u2009\u00b1\u20090.1\u00a0mg\/dL), oxidative imbalance, disrupted autophagic signaling, and histological liver damage. Post-injury treatment with BRB-BSA NPs significantly reduced serum uric acid (0.20\u2009\u00b1\u20090.07\u00a0mg\/dL,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05 vs. DEN\/CCl\n                    <jats:sub>4<\/jats:sub>\n                    ), surpassing the prophylactic regimen and restoring levels comparable to healthy controls. Oxidative status improved, with increased superoxide dismutase (SOD) activity and reduced nitric oxide (NO) and xanthine oxidase (XO) levels. Autophagic signaling was normalized through downregulation of PI3K, mTOR, and p62, alongside upregulation of LC3, indicating restoration of autophagic flux. Apoptotic balance shifted toward pro-apoptotic signaling, with elevated Bax and reduced Bcl-2 expression, supporting the therapeutic potential that BRB-BSA NPs may exert. Histological assessment confirmed near-complete hepatic architecture recovery in the treatment group, while the prophylactic group exhibited partial protection. Collectively, these findings highlight the potent therapeutic role of BRB-BSA NPs in reversing DEN\/CCl\n                    <jats:sub>4\u2212<\/jats:sub>\n                    induced hepatic damage by restoring metabolic, oxidative, autophagic, and apoptotic homeostasis, underscoring their promise as a nanoformulated hepatoprotective intervention.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-43119-1","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T11:55:46Z","timestamp":1774612546000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Berberine-entrapped albumin nanoparticles ameliorate chemically induced liver injury by restoring oxidative balance and autophagic-apoptotic crosstalk"],"prefix":"10.1038","volume":"16","author":[{"given":"Heba","family":"Zaied","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed I.","family":"Ashmawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed E.","family":"Abdel Karim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa A.","family":"Ghareeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2117-0677","authenticated-orcid":false,"given":"Abeer","family":"El Wakil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"43119_CR1","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.jhep.2022.09.001","volume":"78","author":"C Berasain","year":"2023","unstructured":"Berasain, C. et al. 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