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Conventional treatments like statins have limitations, including liver damage and resistance, driving interest in natural compounds with multi\u2010target, low\u2010toxicity effects. This study assessed\n                      <jats:italic>Astragalus polysaccharide<\/jats:italic>\n                      (APS), a traditional Chinese medicine component with antioxidant and metabolic\u2010regulatory properties, for its therapeutic effects on hyperlipidemic rats and its mechanism via the miR\u2010128\u20103p\/NRF2\/antioxidant pathway.\nSD rats were grouped into normal, model, simvastatin, and APS. Except normal, all received high\u2010fat diet for 8 weeks to induce hyperlipidemia. Then, APS (700\u00a0mg\/kg) or simvastatin (6.7\u00a0mg\/kg) was administered via gavage for 8 weeks; controls received saline. Serum indices were monitored periodically; pancreatic and hepatic tissues were analyzed histologically and molecularly. In vitro, lipid accumulation was induced in BRL and HepG2 cells with oleic\/palmitic acids (2:1). Optimal APS dose\/time was determined by CCK\u20108; lipid and oxidative markers were measured.\nA high\u2010fat diet caused hyperlipidemia, elevating lipids, body weight, and energy intake. APS reduced glucose\/lipid levels, and transaminase activity and improved pancreatic\/hepatic pathology, including \u03b2\u2010cell function. APS lowered MDA and miR\u2010128\u20103p while boosting T\u2010SOD and hepatic NRF2. In cells, APS reversed lipid buildup and oxidative stress.\nAPS mitigates hyperlipidemia via the miR\u2010128\u20103p\/NRF2\/antioxidant pathway, providing a multi\u2010target strategy for lipid metabolism, oxidative stress, and organ protection. This supports natural interventions for hyperlipidemia, especially with glucose\/organ issues, meriting clinical exploration.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1750-3841.71035","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T06:40:41Z","timestamp":1775889641000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astragalus Polysaccharide Alleviates Hyperlipidemia via the miR\u2010128\u20103p\/NRF2\/Antioxidant Pathway"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0102-6136","authenticated-orcid":false,"given":"Qianfa","family":"Yuan","sequence":"first","affiliation":[{"name":"Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen Xian Yue Hospital Xian Yue Hospital Affiliated with Xiamen Medical College  Xiamen Fujian China"},{"name":"Department of Biochemistry 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