{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:55:32Z","timestamp":1792018532839,"version":"4.4.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:p>Hyperhomocysteinemia, an elevation of blood homocysteine levels, is a metabolic disorder associated with dysfunction of multiple organs. We previously demonstrated that hyperhomocysteinemia stimulated hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase leading to hepatic lipid accumulation and liver injury. The liver plays an important role in cholesterol biosynthesis and overall homeostasis. HMG-CoA reductase catalyzes the rate-limiting step in cholesterol biosynthesis. Hepatic HMG-CoA reductase is a major target for lowering cholesterol levels in patients with hypercholesterolemia. The aim of the present study was to examine the effect of berberine, a plant-derived alkaloid, on hepatic cholesterol biosynthesis in hyperhomocysteinemic rats and to identify the underlying mechanism. Hyperhomocysteinemia was induced in Sprague-Dawley rats by feeding a high-methionine diet for 4 wk. HMG-CoA reductase activity was markedly elevated in the liver of hyperhomocysteinemic rats, which was accompanied by hepatic lipid accumulation. Activation of HMG-CoA reductase was caused by an increase in its gene expression and a reduction in its phophorylation (an inactive form of the enzyme). Treatment of hyperhomocysteinemic rats with berberine for 5 days inhibited HMG-CoA reductase activity and reduced hepatic cholesterol content. Such an inhibitory effect was mediated by increased phosphorylation of HMG-CoA reductase. Berberine treatment also improved liver function. These results suggest that berberine regulates hepatic cholesterol biosynthesis via increased phosphorylation of HMG-CoA reductase. Berberine may be therapeutically useful for the management of cholesterol homeostasis.<\/jats:p>","DOI":"10.1152\/ajpregu.00441.2010","type":"journal-article","created":{"date-parts":[[2010,12,23]],"date-time":"2010-12-23T04:23:08Z","timestamp":1293078188000},"page":"R635-R643","source":"Crossref","is-referenced-by-count":40,"title":["Regulation of hepatic cholesterol biosynthesis by berberine during hyperhomocysteinemia"],"prefix":"10.1152","volume":"300","author":[{"given":"Nan","family":"Wu","sequence":"first","affiliation":[{"name":"St. Boniface Hospital Research Centre, Winnipeg, Canada;"},{"name":"Physiology, University of Manitoba, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsei K.","family":"Sarna","sequence":"additional","affiliation":[{"name":"St. Boniface Hospital Research Centre, Winnipeg, Canada;"},{"name":"Departments of 2Animal Science and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaw L.","family":"Siow","sequence":"additional","affiliation":[{"name":"St. Boniface Hospital Research Centre, Winnipeg, Canada;"},{"name":"Physiology, University of Manitoba, Canada; and"},{"name":"Agriculture and Agri-Food Canada, Ottawa, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karmin","family":"O","sequence":"additional","affiliation":[{"name":"St. Boniface Hospital Research Centre, Winnipeg, Canada;"},{"name":"Departments of 2Animal Science and"},{"name":"Physiology, University of Manitoba, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000181761.16341.2b"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000108264.67601.2C"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(73)91137-6"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.9.4375"},{"key":"B5","doi-asserted-by":"crossref","first-page":"13228","DOI":"10.1016\/S0021-9258(18)45191-5","volume":"262","author":"Beg ZH","year":"1987","journal-title":"J Biol Chem"},{"key":"B6","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1016\/S0021-9258(18)89648-X","volume":"260","author":"Beg ZH","year":"1985","journal-title":"J Biol Chem"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M600488-JLR200"},{"key":"B8","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0022-2275(20)42221-7","volume":"21","author":"Brown MS","year":"1980","journal-title":"J Lipid Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/science.3513311"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1989.tb15186.x"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-008-9089-3"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1990.tb07420.x"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1972.tb07247.x"},{"key":"B14","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","volume":"226","author":"Folch J","year":"1957","journal-title":"J Biol Chem"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-199405030-00006"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2005.03891.x"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1270"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000196651.64776.51"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.44.27879"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.04.001"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215593"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.5.819"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.4.2.2153592"},{"key":"B24","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/S0022-2275(20)32008-3","volume":"41","author":"Jurevics H","year":"2000","journal-title":"J Lipid Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2004.12.003"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1979.03290450033020"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nm1135"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.08.060"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0006"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01364.x"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.06.034"},{"key":"B32","first-page":"452","volume":"41","author":"Luo LJ","year":"1955","journal-title":"Chin J Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl043"},{"key":"B34","first-page":"111","volume":"56","author":"McCully KS","year":"1969","journal-title":"Am J Pathol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530190040032"},{"key":"B36","doi-asserted-by":"crossref","first-page":"6810","DOI":"10.1016\/S0021-9258(17)37448-3","volume":"269","author":"Omkumar RV","year":"1994","journal-title":"J Biol Chem"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1042\/bj3480607"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004793200"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1139\/Y09-136"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20149"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7254.2007.00705.x"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1552"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.152629"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11596"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.05.012"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000214981.58499.32"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707886200"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00518.2004"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.132142"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00441.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T05:00:31Z","timestamp":1637038831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpregu.00441.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2011,3]]}},"alternative-id":["10.1152\/ajpregu.00441.2010"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00441.2010","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3]]}}}