{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:28:09Z","timestamp":1792189689364,"version":"4.4.0"},"reference-count":71,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The increasing use of red yeast rice (RYR) as a natural supplement to manage blood cholesterol levels is driven by its active compound, monacolin K (MK), which is chemically identical to the statin drug lovastatin (LOV). Despite its growing popularity, concerns persists regarding the safety and efficacy of RYR compared to pure statins. This study aimed to evaluate the phytochemical composition, pharmacological effects, and safety profile of various RYR samples in comparison with LOV. RYR samples with different MK content were analyzed using HPLC\u2010DAD to quantify monacolins and other bioactive compounds. The inhibitory activity on HMG\u2010CoA reductase was assessed through an enzymatic assay, while pharmacokinetic properties were predicted using in\u00a0vitro simulated digestion and\n                    <jats:italic>in silico<\/jats:italic>\n                    models. In\u00a0vitro cytotoxicity was evaluated in intestinal, hepatic, renal, and skeletal muscle cell models. Additionally, the transcriptional levels of muscle damage\u2010related target genes were evaluated by qRT\u2010PCR in skeletal muscle cells treated with a selection of RYR samples. Significant variability in the phytochemical composition of RYR samples\u00a0was observed, particularly in the content of secondary monacolins, triterpenes, and polyphenols. The RYR phytocomplex exhibited superior inhibition of HMG\u2010CoA reductase activity compared to isolated LOV, suggesting synergistic effects between secondary monacolins and other compounds. Molecular insights revealed that RYR samples had a lower impact on muscle cells than LOV, as reflected also by cell viability. These findings suggest that RYR could serve as a safe alternative to purified statins. However, further research is needed to fully elucidate the mechanisms behind the synergistic activity of the phytocomplex and to firmly establish the clinical efficacy of this natural product.\n                  <\/jats:p>","DOI":"10.1002\/ptr.8371","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T23:58:37Z","timestamp":1731023917000},"page":"264-281","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Red Yeast Rice or Lovastatin? A Comparative Evaluation of Safety and Efficacy Through a Multifaceted Approach"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8853-4431","authenticated-orcid":false,"given":"Giovanna","family":"Rigillo","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7221-3277","authenticated-orcid":false,"given":"Giulia","family":"Baini","sequence":"additional","affiliation":[{"name":"Department of Physical Sciences, Earth and Environment University of Siena  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Food and Drug University of Parma  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Puja","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Modena and Reggio Emilia  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Miraldi","sequence":"additional","affiliation":[{"name":"Department of Physical Sciences, Earth and Environment University of Siena  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Pani","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia  Modena Italy"},{"name":"Department of Psychiatry and Behavioral Sciences University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Tascedda","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Modena and Reggio Emilia  Modena Italy"},{"name":"CIB, Consorzio Interuniversitario Biotecnologie  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Biagi","sequence":"additional","affiliation":[{"name":"Department of Food and Drug University of Parma  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/426168"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000163840.63685.0C"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JPBA.2014.07.039"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.ATHEROSCLEROSISSUP.2019.08.023"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.PHRS.2022.106370"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010150\u201012\u2010200906160\u201000006"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40064\u2010016\u20102197\u20102"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BBAGRM.2018.02.008"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/FOODS10112595"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/14017431.2012.734635"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/MICROORGANISMS9122427"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8926075"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1089\/ARS.2014.6190"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2010.179"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00500"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08\u2010128843"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/127043"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.IJPHARM.2013.01.028"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X22666240705143649"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.14797\/MDCJ\u201015\u20103\u2010192"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/NU15102288\/S1"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JACC.2020.11.056"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.4149\/gpb_2021017"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.IJBIOMAC.2018.04.170"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.02.029"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.2903\/J.EFSA.2011.2304"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014\u20105793(76)80996\u20109"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.PHRS.2019.02.028"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00298"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0092265"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00217\u2010021\u201003864\u20101\/FIGURES\/3"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/JAPPLPHYSIOL.01026.2004"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.AMJCARD.2009.08.672"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32741"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.15414\/JMBFS.2018.7.5.454\u2010456"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1749\u20108546\u20107\u20108"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JACC.2022.10.013"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/MOLECULES26206301"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2008.03224.x"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JPBA.2005.03.005"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JPBA.2004.04.004"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1749\u20108546\u20101\u20104"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/JF000338C\/SUPPL_FILE\/JF000338C_S.PDF"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476\u2010511X\u201013\u2010131"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.285577"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1995.1058"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1503\/CMAJ.081785"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen\u20102019\u2010032755"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/JCPT.12374"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.PHRS.2022.106402"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CLPT.2005.03.006"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/S10295\u2010012\u20101216\u20108"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/CELLS10071816"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm_00000274"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/COSMETICS9010012\/S1"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15010240"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/FNUT.2021.792529\/FULL"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.FBIO.2022.102112"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100039\u20103400011"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24101944"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-810422-4.00029-4"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0366-6999.20141199"},{"key":"e_1_2_12_65_1","unstructured":"Tretter E. andN. L.Parinandi.2015.\u201cStatins the Cholesterol\u2010Lowering Drugs Cause Myotoxicity Through Phospholipase D\u2010Mediated Lipid Signaling in Skeletal C2C12 Myoblast Cell.\u201d(Doctoral dissertation The Ohio State University)."},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.23812\/J.BIOL.REGUL.HOMEOST.AGENTS.20233711.555"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods12112142"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/edm2.314"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.STEMCR.2018.01.027"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.2903\/J.EFSA.2018.5368"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3RA04374F"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.3389\/FPHAR.2019.01449\/BIBTEX"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.8371","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T09:37:37Z","timestamp":1737365857000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.8371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,7]]},"references-count":71,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/ptr.8371"],"URL":"https:\/\/doi.org\/10.1002\/ptr.8371","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,7]]},"assertion":[{"value":"2024-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}