{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:40:23Z","timestamp":1792024823830,"version":"4.4.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004054","name":"King Abdulaziz University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold>The star fruit [<jats:italic>Averrhoa carambola<\/jats:italic>L (Oxalidaceae)] is traditionally used in the treatment of many ailments in many countries. It possesses several pharmacological activities, including antioxidant and anti-inflammatory effects. However, it contains the neurotoxic caramboxin and its high content of oxalic acid limits its consumption by individuals with compromised kidney function. This study assessed the anti-hyperlipidemic and antioxidant activities of different fractions of the methanolic extract of<jats:italic>A. carambola<\/jats:italic>leaves (MEACL).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold>The antioxidant activity was investigated using FRAP, and ABTS and DPPH radical-scavenging assays and the inhibitory activity toward pancreatic lipase (PL) and HMG-CoA reductase was assayed<jats:italic>in vitro<\/jats:italic>. Acute hyperlipidemia was induced by poloxamer-407 (P-407) in rats and different fractions of MEACL (<jats:italic>n<\/jats:italic>-hexane, chloroform,<jats:italic>n<\/jats:italic>-butanol, ethyl acetate (EA), water, and chloroform) were orally administered. Cholesterol and triglycerides were determined at 0, 12, 24, and 48\u00a0h and LDL-C, vLDL-C, HDL-C, lipid peroxidation (LPO) and antioxidants were assayed after 48\u00a0h. The expression of ABCA1, ABCG5, ABCG8, LDL-R, SREBP-1, and SREBP-2 and the activity of HMG-CoA reductase were assayed in the liver of P-407-administered rats treated with the EA fraction.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold>The<jats:italic>in vitro<\/jats:italic>data revealed potent radical-scavenging activities of MEACL fractions with the most potent effect showed by the EA fraction that also suppressed the activities of HMG-CoA reductase and PL. In P-407-induced hyperlipidemic rats, all fractions prevented dyslipidemia as shown by the decrease in total cholesterol, triglycerides, LDL-C, vLDL-C and atherogenic index. MEACL and its fractions prevented LPO and boosted GSH, superoxide dismutase, glutathione peroxidase, and catalase in P-407-administered rats. The EA fraction showed more effective anti-hyperlipidemic and antioxidant effects than other fractions and downregulated SREBP-2 while upregulated ABCA1 and LDL-R and ameliorated LPL and HMG-CoA reductase in hyperlipidemic rats.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold>MEACL showed<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>antioxidant activity and the EA fraction significantly ameliorated dyslipidemia in a rat model of P-407-induced acute hyperlipidemia by modulating LPL, PL, HMG-CoA reductase, and cholesterolgenesis-related factors. Therefore, the leaves of<jats:italic>A. carambola<\/jats:italic>represent a safe alternative for the star fruit particularly in kidney disease patients, and the EA is the most effective anti-hyperlipidemic and antioxidant fraction.<\/jats:p>","DOI":"10.3389\/fphar.2023.1134812","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T05:28:31Z","timestamp":1675661311000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Averrhoa carambola leaves prevent dyslipidemia and oxidative stress in a rat model of poloxamer-407-induced acute hyperlipidemia"],"prefix":"10.3389","volume":"14","author":[{"given":"Maisa Siddiq","family":"Abduh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sultan A. 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