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Preliminary studies have demonstrated that <jats:italic>Ficus Lyrata<\/jats:italic> leaves can exert protective effects in rats against hepatic fibrosis and hypercholesterolemia. Hence, this study was conducted to investigate the therapeutic effect of <jats:italic>Ficus lyrata<\/jats:italic> Wrab bark extract on the NAFLD rat model. NAFLD was induced through a high-fat diet (HFD) for 12 weeks in male Wistar rats. After four weeks of HFD feeding, the rats were treated with <jats:italic>F. lyrata<\/jats:italic> extract (250\u00a0mg\/kg, 5 days\/week) or simvastatin (4\u00a0mg\/kg, 5 days\/week) while continuing on the HFD till the end of the experiment. Serum and liver samples were harvested for biochemical, molecular, histopathological, and immunohistochemical investigations. In silico analysis was also conducted to analyse the binding affinity of the extract polyphenols and the key regulators of hepatic lipogenesis. The results revealed that <jats:italic>F. lyrata<\/jats:italic> extract administered to HFD-fed rats significantly improved the characteristics of NAFLD by reducing hyperglycemia, hyperinsulinemia, and aminotransferases while improving serum lipid profile and adipokines. Moreover, the extract reduced the expression of hepatic lipogenic genes sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase-1 (ACC-1), and fatty acid synthase (FAS), and inflammatory markers tumour necrosis factor-\u03b1 (TNF-\u03b1) and interleukin-6 (IL-6), along with modulating oxidative stress markers and reversing histopathological changes. Molecular docking study revealed that most polyphenolic compounds in <jats:italic>F. lyrata<\/jats:italic> extract exhibited good binding affinity towards peroxisome proliferator-activated receptors \u03b3 (PPAR-\u03b3) and liver X receptor \u03b1 (LXR-\u03b1). In conclusion, our findings suggested that <jats:italic>F. lyrata<\/jats:italic> bark could be a promising therapeutic agent against the health issues related to NAFLD.<\/jats:p>","DOI":"10.1186\/s12906-025-05010-w","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T14:28:24Z","timestamp":1752935304000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Chemical profile of Ficus lyrata bark extract and its therapeutic effect on non-alcoholic fatty liver disease via regulating oxidative stress, inflammation and hepatic lipogenesis"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9677-9041","authenticated-orcid":false,"given":"Amria Mamdouh","family":"Mousa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab Fikry","family":"Taher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nermin Mohamed","family":"El-Sammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esraa Aly","family":"Balabel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham Mohamed","family":"Youssef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Hassan","family":"Afifi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar Samir","family":"Abdel-Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayera","family":"Anwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherien Kamal","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,19]]},"reference":[{"key":"5010_CR1","doi-asserted-by":"publisher","first-page":"706978","DOI":"10.3389\/fendo.2021.706978","volume":"12","author":"X Lin","year":"2021","unstructured":"Lin X, Li H. 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