{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:19:36Z","timestamp":1789647576141,"version":"4.0.0"},"reference-count":15,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Project of State Key Laboratory of Natural Medicines, China Pharmaceutical University","award":["SKLNMZZ202005"],"award-info":[{"award-number":["SKLNMZZ202005"]}]},{"name":"\u201cDouble First-Class\u201d University Project","award":["CPU2018GY17"],"award-info":[{"award-number":["CPU2018GY17"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81800512"],"award-info":[{"award-number":["81800512"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31771298"],"award-info":[{"award-number":["31771298"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31800992"],"award-info":[{"award-number":["31800992"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Postgraduate Research & Practice Innovation Program of Jiangsu Province, China","award":["KYCX18_0781"],"award-info":[{"award-number":["KYCX18_0781"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The chronopharmacology refers to the utilization of physiological circadian rhythms to optimize the administration time of drugs, thus increasing their efficacy and safety, or reducing adverse effects. Simvastatin is one of the most widely prescribed drugs for the treatment of hypercholesterolaemia, hyperlipidemia and coronary artery disease. There are conflicting statements regarding the timing of simvastatin administration, and convincing experimental evidence remains unavailable. Thus, we aimed to examine whether different administration times would influence the efficacy of simvastatin. High\u2010fat diet\u2010fed mice were treated with simvastatin at zeitgeber time 1 (ZT1) or ZT13, respectively, for nine weeks. Simvastatin showed robust anti\u2010hypercholesterolaemia and anti\u2010hyperlipidemia effects on these obese mice, regardless of administration time. However, simvastatin administrated at ZT13, compared to ZT1, was more functional for decreasing serum levels of total cholesterol, triglycerides, non\u2010esterified free fatty acids and LDL cholesterol, as well as improving liver pathological characteristics. In terms of possible mechanisms, we found that simvastatin did not alter the expression of hepatic circadian clock gene in vivo, although it failed to change the period, phase and amplitude of oscillation patterns in Per2::Luc U2OS and Bmal1::Luc U2OS cells in vitro. In contrast, simvastatin regulated the expression of Hmgcr, Mdr1 and Slco2b1 in a circadian manner, which potentially contributed to the chronopharmacological function of the drug. Taken together, we provide solid evidence to suggest that different administration times affect the lipid\u2010lowering effects of simvastatin.<\/jats:p>","DOI":"10.1111\/jcmm.15709","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T08:03:17Z","timestamp":1596787397000},"page":"11024-11029","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Chronopharmacology of simvastatin on hyperlipidaemia in high\u2010fat diet\u2010fed obese mice"],"prefix":"10.1111","volume":"24","author":[{"given":"Huan","family":"Li","sequence":"first","affiliation":[{"name":"School of Life Sciences and Technology China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjara","family":"Rabearivony","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"An","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2285-1554","authenticated-orcid":false,"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-011613-135923"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1408886111"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2016.03.004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah4967"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.21037\/arh.2018.12.01"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200847070-00003"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-020-6639-4"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7418.788"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.11.4.816"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2013.06.020"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1P511"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02977789"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.55"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:PHAM.0000041466.84653.8c"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2011.10.005"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.15709","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.15709","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.15709","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.15709","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T13:00:52Z","timestamp":1692536452000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.15709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,7]]},"references-count":15,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1111\/jcmm.15709"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.15709","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,7]]},"assertion":[{"value":"2020-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}