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Recent researchers have identified a potential role of proprotein convertase subtilisin\/kexin type 9 (PCSK9) in modulating lipid metabolism and reducing plasma low density lipoprotein (LDL) levels. PCSK9 is the central protein in the metabolism of LDL cholesterol (LDL\u2010C) owing to its major function in LDL receptor (LDLR) degradation. Due to the close correlation of cardiovascular disease with lipid levels, many in vivo and in vitro investigations are currently underway studying the physiological role of PCSK9. Furthermore, many studies are actively investigating the mechanisms of various compounds that influence lipid associated\u2010disorders and their associated cardiovascular diseases. PCSK9 inhibitors have been shown to have significant impact in the prevention of emerging cardiovascular diseases. Natural products can effectively be used as PCSK9 inhibitors to control lipid levels through various mechanisms. In this review, we evaluate the role of phytochemicals and natural products in the regulation of PCSK9, and their ability to prevent cardiovascular diseases. Moreover, we describe their mechanisms of action, which have not to date been delineated.<\/jats:p>","DOI":"10.1002\/ptr.8260","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T10:58:14Z","timestamp":1718881094000},"page":"4081-4098","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The role of natural products as <scp>PCSK9<\/scp> modulators: A review"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-9076","authenticated-orcid":false,"given":"Danial","family":"Khayatan","sequence":"first","affiliation":[{"name":"Department of Toxicology &amp; Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences Islamic Azad University  Tehran Iran"},{"name":"GI Pharmacology Interest Group (GPIG) Universal Scientific Education and Research Network (USERN)  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimia","family":"Zare","sequence":"additional","affiliation":[{"name":"School of Medicine Shahid Sadoughi University of Medical Sciences and Health Services  Yazd Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Khanahmadi","sequence":"additional","affiliation":[{"name":"Department of Toxicology &amp; Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences Islamic Azad University  Tehran Iran"},{"name":"GI Pharmacology Interest Group (GPIG) Universal Scientific Education and Research Network (USERN)  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeideh","family":"Momtaz","sequence":"additional","affiliation":[{"name":"Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR  Tehran Iran"},{"name":"Department of Toxicology and Pharmacology, School of Pharmacy, and Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS) Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-3917","authenticated-orcid":false,"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[{"name":"Royal College of Surgeons in Ireland Bahrain  Adliya Bahrain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9521-3153","authenticated-orcid":false,"given":"Tannaz","family":"Jamialahmadi","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Center, Pharmaceutical Technology Institute Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Medical Toxicology Research Center Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wael","family":"Almahmeed","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute, Cleveland Clinic Abu Dhabi  Abu Dhabi United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9961-9097","authenticated-orcid":false,"given":"Amir Hossein","family":"Abdolghaffari","sequence":"additional","affiliation":[{"name":"Department of Toxicology &amp; Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences Islamic Azad University  Tehran Iran"},{"name":"GI Pharmacology Interest Group (GPIG) Universal Scientific Education and Research Network (USERN)  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8656-1444","authenticated-orcid":false,"given":"Amirhossein","family":"Sahebkar","sequence":"additional","affiliation":[{"name":"Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences Saveetha University  Chennai India"},{"name":"Biotechnology Research Center, Pharmaceutical Technology Institute Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Applied Biomedical Research Center Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,6,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S144121"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2018.06.041"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106414"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11030463"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/0973-7847.112853"},{"key":"e_1_2_9_7_1","unstructured":"Armenia E. 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