{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T18:29:11Z","timestamp":1788114551744,"version":"build-2803163510"},"reference-count":79,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah Bint Abdulrahman University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hyperlipidemia is a common clinically encountered health condition worldwide that promotes the development and progression of cardiovascular diseases, including atherosclerosis. Berberine (BBR) is a natural product with acknowledged anti\u2010inflammatory, antioxidant, and metabolic effects. This study evaluated the effect of BBR on lipid alterations, oxidative stress, and inflammatory response in rats with acute hyperlipidemia induced by poloxamer\u2010407 (P\u2010407). Rats were pretreated with BBR (25 and 50\u2009mg\/kg) for 14 days and acute hyperlipidemia was induced by a single dose of P\u2010407 (500\u2009mg\/kg). BBR ameliorated hypercholesterolemia, hypertriglyceridemia, and plasma lipoproteins in P\u2010407\u2010adminsitered rats. Plasma lipoprotein lipase (LPL) activity was decreased, and hepatic 3\u2010hydroxy\u20103\u2010methylglutaryl CoA (HMG\u2010CoA) reductase activity was enhanced in hyperlipidemic rats. The expression of low\u2010density lipoprotein receptor (LDL\u2010R) and ATP\u2010binding cassette transporter 1 (ABCA1) was downregulated in hyperlipidemic rats. BBR enhanced LPL activity, upregulated LDL\u2010R, and ABCA1, and suppressed HMG\u2010CoA reductase\u00a0in P\u2010407\u2010administered rats. Pretreatment with BBR ameliorated lipid peroxidation, nitric oxide (NO), pro\u2010inflammatory mediators (interleukin [IL]\u20106,\u00a0IL\u20101\u03b2, tumor necrosis factor [TNF]\u2010\u03b1, interferon\u2010\u03b3, IL\u20104 and IL\u201018) and enhanced antioxidants. In addition, BBR suppressed lymphocyte ecto\u2010nucleoside triphosphate diphosphohydrolase (E\u2010NTPDase) and ecto\u2010adenosine deaminase (E\u2010ADA) as well as NO and TNF\u2010\u03b1 release by macrophages isolated from normal and hyperlipidemic rats. In silico investigations revealed the binding affinity of BBR toward\u00a0LPL, HMG\u2010CoA reductase, LDL\u2010R, PSK9, ABCA1, and E\u2010NTPDase. In conclusion, BBR effectively prevented acute hyperlipidemia and its associated inflammatory responses by modulating LPL, cholesterolgenesis, cytokine release, and lymphocyte E\u2010NTPDase and E\u2010ADA. Therefore, BBR is an effective and safe natural compound that might be employed as an adjuvant against hyperlipidemia and its associated inflammation.<\/jats:p>","DOI":"10.1002\/ddr.22166","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:25:51Z","timestamp":1709252751000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Berberine attenuates inflammation and oxidative stress and modulates lymphocyte E\u2010NTPDase in acute hyperlipidemia"],"prefix":"10.1002","volume":"85","author":[{"given":"Reem S.","family":"Alruhaimi","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science Princess Nourah bint Abdulrahman University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7231-3386","authenticated-orcid":false,"given":"Maisa","family":"Siddiq Abduh","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Immune Responses in Different Diseases Research Group, Faculty of Applied Medical Sciences King Abdulaziz University Jeddah Saudi Arabia"},{"name":"Center of Excellence in Genomic Medicine Research King Abdulaziz University Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5962-9573","authenticated-orcid":false,"given":"Ahmad F.","family":"Ahmeda","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine Ajman University Ajman United Arab Emirates"},{"name":"Center of Medical and Bio\u2010allied Health Sciences Research Ajman University Ajman United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albandari","family":"Bin\u2010Ammar","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, College of Applied Medical Sciences University of Hail Ha'il Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emadeldin M.","family":"Kamel","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science Beni\u2010Suef University Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4865-2342","authenticated-orcid":false,"given":"Emad H. M.","family":"Hassanein","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology, Faculty of Pharmacy Al\u2010Azhar University\u2010Assiut Branch Assiut Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biology, Chemistry, Pharmacy Free University of Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0279-6500","authenticated-orcid":false,"given":"Ayman M.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Faculty of Science and Engineering Manchester Metropolitan University Manchester UK"},{"name":"Zoology Department,\u00a0Physiology Division, Faculty of Science Beni\u2010Suef University Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1134812"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0076-6879(84)05016-3"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c170012"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.120260"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13351"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab037"},{"key":"e_1_2_10_8_1","first-page":"77","article-title":"Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g","volume":"97","author":"B\u00f6yum A.","year":"1968","journal-title":"Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.26"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-017-3231-6"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci27352"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.116.309726"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27102"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(86)90640-8"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.18433\/J37G7M"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0891-5849(00)00344-0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2013.02.028"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M500531-JLR200"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90090-6"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.30787"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0076-6879(84)05015-1"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci21625"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-014-1665-8"},{"key":"e_1_2_10_25_1","first-page":"315","volume-title":"Methods of enzymatic analysis","author":"Giusti G.","year":"1984"},{"issue":"1","key":"e_1_2_10_26_1","first-page":"19","article-title":"Low\u2010density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis","volume":"85","author":"Go G. W.","year":"2012","journal-title":"The Yale Journal of Biology and Medicine"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(82)90118-X"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.937201"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215593"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf071868c"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2012.1236"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90599.2008"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(93)90668-m"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1388-1981(00)00151-7"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.5213\/inj.1938216.108"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2015.11.010"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1135"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-016-0186-7"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2008.06.010"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2004.09.006"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-0276-8"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-005-1377-2"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.07.101"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc3901.096721"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(85)90216-7"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(79)90738-3"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2016.03.007"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.5213\/inj.2142342.171"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/152786"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.037085"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/2047-783x-15-s2-120"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14935"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26237368"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.11.010"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2019.1624767"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13111"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1247\/csf.20.421"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.231043"},{"issue":"5","key":"e_1_2_10_60_1","first-page":"1204","article-title":"Study of oxidative stress in hypercholesterolemia","volume":"4","author":"Singh U. N.","year":"2017","journal-title":"International Journal of Contemporary Medical Research"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-019-0724-6"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-013-0310-3"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(99)00065-9"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.ima03bs111"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2022.01.006"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.116.106617"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2005.09.016"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.08.050"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2014.05.013"},{"issue":"2","key":"e_1_2_10_70_1","first-page":"189","article-title":"Poloxamer 407\u2010mediated alterations in the activities of enzymes regulating lipid metabolism in rats","volume":"6","author":"Wasan K. M.","year":"2003","journal-title":"Journal of Pharmacy & Pharmaceutical Sciences"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152097"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.2008044"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(97)00881-8"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.04.016"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2008.01.013"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci16001"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.indcrop.2013.11.041"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806312105"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-017-0165-7"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.10.001"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.22166","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T21:13:30Z","timestamp":1760390010000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.22166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,29]]},"references-count":79,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/ddr.22166"],"URL":"https:\/\/doi.org\/10.1002\/ddr.22166","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,29]]},"assertion":[{"value":"2023-07-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22166"}}