{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:06:33Z","timestamp":1790784393053,"version":"4.1.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011447","name":"Science and Technology Department of Henan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Coronary atherosclerotic heart disease, cerebrovascular disease, and peripheral artery disease are common diseases with high morbidity and mortality rates and must be addressed. Their most frequent complications, including myocardial infarction and stroke, are caused by spontaneous thrombotic occlusion and are the most frequent cause of death worldwide. Atherosclerosis (AS) is the most widespread underlying pathological change for the above diseases. Therefore, drugs that interfere with this pathophysiological process must be incorporated in the treatment. Chinese traditional and herbal drugs can effectively treat AS. With the development of traditional Chinese medicine, the active ingredients in common Chinese medicinal materials must be thoroughly purified prior to their application in western medicine. Various proprietary Chinese medicine preparations with remarkable effects have been used in AS treatment. Catalpol, the active component of <jats:italic>Rehmannia glutinosa<\/jats:italic>, belongs to iridoid terpene and has anti-inflammatory, antioxidant, insulin resistance improvement, and other related effects. Several reviews have been conducted on this compound and its actions against osteoporosis, neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease (PD) and diabetes and its complications. The current review focused on catalpol\u2019s effect on atherosclerotic plaque formation in different animal models. The potential mechanisms of catalpol to ameliorate AS were also summarized in terms of oxidative stress, inflammation, cell aging, apoptosis, and activation of the silent information regulator factor 2-related enzyme 1 (SIRT1) pathway.<\/jats:p>","DOI":"10.3389\/fphar.2021.716125","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T05:10:45Z","timestamp":1626153045000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Research Progress on Catalpol as Treatment for Atherosclerosis"],"prefix":"10.3389","volume":"12","author":[{"given":"Lei","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rusheng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huibing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3302","DOI":"10.3390\/molecules24183302","article-title":"Catalpol in Diabetes and its Complications: A Review of Pharmacology, Pharmacokinetics, and Safety","volume":"24","author":"Bai","year":"2019","journal-title":"Molecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.1172\/jci117917","article-title":"Apoptosis of Human Vascular Smooth Muscle Cells Derived from normal Vessels and Coronary Atherosclerotic Plaques","volume":"95","author":"Bennett","year":"1995","journal-title":"J. Clin. Invest."},{"key":"B3","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/s1383-5718(01)00162-0","article-title":"Evidence for DNA Damage in Patients with Coronary Artery Disease","volume":"493","author":"Botto","year":"2001","journal-title":"Mutat. Research\/Genetic Toxicol. Environ. Mutagenesis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s12881-015-0194-x","article-title":"Sequence Variation in Telomerase Reverse Transcriptase (TERT) as a Determinant of Risk of Cardiovascular Disease: the Atherosclerosis Risk in Communities (ARIC) Study","volume":"16","author":"Bressler","year":"2015","journal-title":"BMC Med. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"655081","DOI":"10.3389\/fphar.2021.655081","article-title":"Catalpol Inhibits Macrophage Polarization and Prevents Postmenopausal Atherosclerosis through Regulating Estrogen Receptor Alpha","volume":"12","author":"Chen","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1111\/bph.13517","article-title":"Targeting Vascular (Endothelial) Dysfunction","volume":"174","author":"Daiber","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/s0092-8674(00)80405-5","article-title":"Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery","volume":"91","author":"Datta","year":"1997","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.1101\/gad.1346005","article-title":"Shelterin: the Protein Complex that Shapes and Safeguards Human Telomeres","volume":"19","author":"De Lange","year":"2005","journal-title":"Genes Development"},{"key":"B9","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.ejmech.2019.03.009","article-title":"Therapeutic Potentials of Plant Iridoids in Alzheimer's and Parkinson's Diseases: A Review","volume":"169","author":"Dinda","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3184","DOI":"10.12659\/msm.907569","article-title":"Efficacy, Safety, and Cost of Therapy of the Traditional Chinese Medicine, Catalpol, in Patients Following Surgical Resection for Locally Advanced Colon Cancer","volume":"24","author":"Fei","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"B11","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.intimp.2014.07.011","article-title":"Protective Effect of Catalpol on Lipopolysaccharide-Induced Acute Lung Injury in Mice","volume":"23","author":"Fu","year":"2014","journal-title":"Int. Immunopharmacology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1093\/eurheartj\/ehu071","article-title":"Non-coronary Atherosclerosis","volume":"35","author":"Gallino","year":"2014","journal-title":"Eur. Heart J."},{"key":"B13","doi-asserted-by":"publisher","first-page":"259","DOI":"10.3109\/07853890.2010.543920","article-title":"Oxidative Stress and Endothelial Dysfunction: Therapeutic Implications","volume":"43","author":"Gori","year":"2011","journal-title":"Ann. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1007\/s10753-018-0873-9","article-title":"Catalpol Inhibits Homocysteine-Induced Oxidation and Inflammation via Inhibiting Nox4\/NF-\u039ab and GRP78\/PERK Pathways in Human Aorta Endothelial Cells","volume":"42","author":"Hu","year":"2019","journal-title":"Inflammation"},{"key":"B15","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.ejphar.2009.11.046","article-title":"Catalpol Inhibits Apoptosis in Hydrogen Peroxide-Induced Endothelium by Activating the PI3K\/Akt Signaling Pathway and Modulating Expression of Bcl-2 and Bax","volume":"628","author":"Hu","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.13241\/j.cnki.pmb.2008.06.016","article-title":"Protective Effect of Catalpol in Mice Injuries Induced by Rotenone and Evaluation of the Safety of Catalpol","volume":"8","author":"Jang","year":"2008","journal-title":"Prog. Mod. Biomed."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3328","DOI":"10.3390\/ijms20133328","article-title":"The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation","volume":"20","author":"Kelley","year":"2019","journal-title":"Ijms"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.18632\/aging.101068","article-title":"The Protective Role of Sirt1 in Vascular Tissue: its Relationship to Vascular Aging and Atherosclerosis","volume":"8","author":"Kitada","year":"2016","journal-title":"Aging"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.1016\/s0140-6736(18)31668-4","article-title":"Mortality Due to Low-Quality Health Systems in the Universal Health Coverage Era: a Systematic Analysis of Amenable Deaths in 137 Countries","volume":"392","author":"Kruk","year":"2018","journal-title":"The Lancet"},{"key":"B20","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nature10146","article-title":"Progress and Challenges in Translating the Biology of Atherosclerosis","volume":"473","author":"Libby","year":"2011","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5804","DOI":"10.3390\/molecules18055804","article-title":"Dried Root of Rehmannia Glutinosa Prevents Bone Loss in Ovariectomized Rats","volume":"18","author":"Lim","year":"2013","journal-title":"Molecules"},{"key":"B22","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1080\/21655979.2020.1863015","article-title":"Catalpol Ameliorates Psoriasis-like Phenotypes via SIRT1 Mediated Suppression of NF-\u039ab and MAPKs Signaling Pathways","volume":"12","author":"Liu","year":"2021","journal-title":"Bioengineered"},{"key":"B23","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.jep.2017.01.021","article-title":"Rehmanniae Radix in Osteoporosis: A Review of Traditional Chinese Medicinal Uses, Phytochemistry, Pharmacokinetics and Pharmacology","volume":"198","author":"Liu","year":"2017","journal-title":"J. Ethnopharmacology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1055\/s-0034-1396240","article-title":"Amelioration by Catalpol of Atherosclerotic Lesions in Hypercholesterolemic Rabbits","volume":"81","author":"Liu","year":"2015","journal-title":"Planta Med."},{"key":"B25","first-page":"4278","article-title":"Catalpol Ameliorates Diabetic Atherosclerosis in Diabetic Rabbits","volume":"8","author":"Liu","year":"2016","journal-title":"Am. J. Transl Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1007\/s11596-014-1359-0","article-title":"Endoplasmic Reticulum Stress-Mediated Aldosterone-Induced Apoptosis in Vascular Endothelial Cells","volume":"34","author":"Lu","year":"2014","journal-title":"J. Huazhong Univ. Sci. Technol. [Med. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1007\/s11883-011-0174-3","article-title":"Atherosclerosis: an Epigenetic Balancing Act that Goes Wrong","volume":"13","author":"Lund","year":"2011","journal-title":"Curr. Atheroscler. Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/s0008-6363(98)00311-3","article-title":"Biphasic Pattern of Cell Turnover Characterizes the Progression from Fatty Streaks to Ruptured Human Atherosclerotic Plaques","volume":"41","author":"Lutgens","year":"1999","journal-title":"Cardiovasc. Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1161\/01.RES.0000233315.38086.bc","article-title":"Vascular Smooth Muscle Cells Undergo Telomere-Based Senescence in Human Atherosclerosis","volume":"99","author":"Matthews","year":"2006","journal-title":"Circ. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.7314\/apjcp.2016.17.4.1993","article-title":"Telomere-Mitochondrion Links Contribute to Induction of Senescence in MCF-7 Cells after Carbon-Ion Irradiation","volume":"17","author":"Miao","year":"2016","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"B31","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.mam.2018.03.002","article-title":"ROS Signaling and ER Stress in Cardiovascular Disease","volume":"63","author":"Ochoa","year":"2018","journal-title":"Mol. Aspects Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1161\/01.ATV.0000117200.46938.e7","article-title":"Telomere Shortening in Human Coronary Artery Diseases","volume":"24","author":"Ogami","year":"2004","journal-title":"Atvb"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1056\/nejm199704173361603","article-title":"Apoptosis in the Failing Human Heart","volume":"336","author":"Olivetti","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1161\/circresaha.114.301174","article-title":"Mechanisms that Regulate Macrophage burden in Atherosclerosis","volume":"114","author":"Randolph","year":"2014","journal-title":"Circ. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1056\/NEJMoa0807646","article-title":"Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein","volume":"359","author":"Ridker","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"857","DOI":"10.3390\/ijms20040857","article-title":"Endoplasmic Reticulum Stress and Unfolded Protein Response in Breast Cancer: The Balance between Apoptosis and Autophagy and its Role in Drug Resistance","volume":"20","author":"Sisinni","year":"2019","journal-title":"Ijms"},{"key":"B37","doi-asserted-by":"publisher","first-page":"353","DOI":"10.18632\/aging.100162","article-title":"SIRT1 Reduces Endothelial Activation without Affecting Vascular Function in ApoE-\/- Mice","volume":"2","author":"Stein","year":"2010","journal-title":"Aging"},{"key":"B38","doi-asserted-by":"publisher","first-page":"18185","DOI":"10.3390\/ijms160818185","article-title":"Exploiting the Pleiotropic Antioxidant Effects of Established Drugs in Cardiovascular Disease","volume":"16","author":"Steven","year":"2015","journal-title":"Ijms"},{"key":"B39","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1161\/circulationaha.106.652693","article-title":"Hyperhomocysteinemia Alters Cardiac Substrate Metabolism by Impairing Nitric Oxide Bioavailability through Oxidative Stress","volume":"115","author":"Suematsu","year":"2007","journal-title":"Circulation"},{"key":"B40","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1161\/01.cir.101.9.948","article-title":"Long-term Follow-Up of Patients with Mild Coronary Artery Disease and Endothelial Dysfunction","volume":"101","author":"Suwaidi","year":"2000","journal-title":"Circulation"},{"key":"B41","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.jchromb.2015.12.007","article-title":"Biotransformation and Metabolic Profile of Catalpol with Human Intestinal Microflora by Ultra-performance Liquid Chromatography Coupled with Quadrupole Time-Of-Flight Mass Spectrometry","author":"Tao","year":"2016","journal-title":"J. Chromatogr. B"},{"key":"B42","doi-asserted-by":"publisher","first-page":"23317","DOI":"10.1074\/jbc.271.38.23317","article-title":"p22 Is a Critical Component of the Superoxide-Generating NADH\/NADPH Oxidase System and Regulates Angiotensin IIinduced Hypertrophy in Vascular Smooth Muscle Cells","volume":"271","author":"Ushio-Fukai","year":"1996","journal-title":"J. Biol. Chem."},{"key":"B43","doi-asserted-by":"publisher","first-page":"117202","DOI":"10.1016\/j.jns.2020.117202","article-title":"A Hypothesis-Generating Scoping Review of miRs Identified in Both Multiple Sclerosis and Dementia, Their Protein Targets, and miR Signaling Pathways","volume":"420","author":"Varma-Doyle","year":"2021","journal-title":"J. Neurol. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"173","DOI":"10.2174\/1389200221999201125205515","article-title":"Detection and Identification of Catalpol Metabolites in the Rat Plasma, Urine and Faeces Using Ultra-high Performance Liquid Chromatography-Q Exactive Hybrid Quadrupole-Orbitrap High-Resolution Accurate Mass Spectrometry","volume":"22","author":"Xiang","year":"2021","journal-title":"Cdm"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1016\/j.celrep.2015.07.047","article-title":"PGC-1\u03b1 Modulates Telomere Function and DNA Damage in Protecting against Aging-Related Chronic Diseases","volume":"12","author":"Xiong","year":"2015","journal-title":"Cel Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.phrs.2017.05.030","article-title":"Activation of Sirtuin 1 by Catalpol-Induced Down-Regulation of microRNA-132 Attenuates Endoplasmic Reticulum Stress in Colitis","volume":"123","author":"Xiong","year":"2017","journal-title":"Pharmacol. Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e54265","DOI":"10.1371\/journal.pone.0054265","article-title":"Homocysteine Inhibits Hepatocyte Proliferation via Endoplasmic Reticulum Stress","volume":"8","author":"Yu","year":"2013","journal-title":"PLoS One"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1038\/sj.onc.1201864","article-title":"The Thiol Crosslinking Agent Diamide Overcomes the Apoptosis-Inhibitory Effect of Bcl-2 by Enforcing Mitochondrial Permeability Transition","volume":"16","author":"Zamzami","year":"1998","journal-title":"Oncogene"},{"key":"B49","doi-asserted-by":"publisher","first-page":"4558","DOI":"10.1111\/bph.14822","article-title":"Catalpol Alleviates Adriamycin\u2010induced Nephropathy by Activating the SIRT1 Signalling Pathway In Vivo and In Vitro","volume":"176","author":"Zhang","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/2876350","article-title":"Activating the PGC-1\u03b1\/TERT Pathway by Catalpol Ameliorates Atherosclerosis via Modulating ROS Production, DNA Damage, and Telomere Function: Implications on Mitochondria and Telomere Link","volume":"2018","author":"Zhang","year":"2018","journal-title":"Oxidative Med. Cell Longevity"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/819053","article-title":"Scropolioside B Inhibits IL-1\u03b2and Cytokines Expression through NF-\u039ab and Inflammasome NLRP3 Pathways","volume":"2014","author":"Zhu","year":"2014","journal-title":"Mediators Inflamm."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.716125\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T05:10:49Z","timestamp":1626153049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.716125\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,13]]},"references-count":51,"alternative-id":["10.3389\/fphar.2021.716125"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.716125","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,13]]},"article-number":"716125"}}