{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:41:42Z","timestamp":1767188502199,"version":"3.48.0"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key project of Natural Science Foundation of Xinjiang Uygur Autonomous Region in China","award":["2022D01D36"],"award-info":[{"award-number":["2022D01D36"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objective: Acteoside (ACT) has different pharmacological properties such as antioxidant, hepatoprotective and anti-inflammatory effects. Impaired mitophagy has been recognized as an important pathogenic factor in metabolic dysfunction-associated steatotic liver disease (MASLD). Nevertheless, the possible therapeutic role of ACT in MASLD and the exact effect of ACT on mitophagy regulation are not explored. This study aims to elucidate the therapeutic efficacy of ACT in a high-fat and high-sugar (HFHS) diet-induced mouse model of MASLD and to determine whether its effects are related to the activation of PINK1\/Parkin-related mitophagy markers. Methods: C57BL\/6J mice were randomly allocated to control, model, rosuvastatin (RSF, 3 mg\/kg), and ACT (30, 60, and 120 mg\/kg) groups. Following a 14-week continuous intervention, biochemical parameters, liver histology, and mitophagy-related markers were assessed. Results: ACT administration significantly improved serum lipid profiles, liver function and insulin resistance, marked by reduced levels of MDA, IL-6, TNF-\u03b1, IL-1\u03b2, LDL-C, TC, TG, AST, ALT, HOMA-IR (p &lt; 0.05), while increasing HDL-C and enhancing hepatic GSH-Px and SOD activities (p &lt; 0.05). Histological examination revealed a notable attenuation of hepatic steatosis and lipid accumulation. At the molecular level, ACT promoted mitophagy activation, as indicated by upregulated PINK1, LC3II\/I, and Parkin expression and downregulated P62 and p-P62. Electron microscopy further validated the restoration of mitochondrial morphology and reduction in lipid droplets. Conclusions: These results demonstrate that ACT ameliorates MASLD progression by improving metabolic homeostasis, reducing inflammation and oxidative stress, and alleviating PINK1\/Parkin-related mitophagy impairment to restore mitophagy homeostasis. Our study highlights the potential of ACT as a new therapeutic agent for MASLD.<\/jats:p>","DOI":"10.3390\/nu18010118","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:30:52Z","timestamp":1767187852000},"page":"118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acteoside Ameliorates Hepatic Steatosis and Liver Injury in MASLD Mice Through Activation of PINK1\/Parkin-Related Mitophagy Markers"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6760-0314","authenticated-orcid":false,"given":"Meili","family":"Cong","sequence":"first","affiliation":[{"name":"School of Public Health, Xinjiang Medical University, Urumqi 830017, China"},{"name":"Animal Laboratory Center, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5945-6289","authenticated-orcid":false,"given":"Xinxin","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Public Health, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongguang","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Public Health, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunxin","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Public Health, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9890-4582","authenticated-orcid":false,"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Public Health, Xinjiang Medical University, Urumqi 830017, China"},{"name":"Xinjiang Key Laboratory for Uighur Medicine, Institute of Materia Medica of Xinjiang, Urumqi 830004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e573","DOI":"10.1016\/j.cgh.2021.02.030","article-title":"Estimating Global Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease in Overweight or Obese Adults","volume":"20","author":"Liu","year":"2022","journal-title":"Clin. 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