{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:26:57Z","timestamp":1789097217724,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007088","name":"statutory funds from the Faculty of Pharmacy, Jagiellonian University Medical College, Cracow, Poland","doi-asserted-by":"publisher","award":["N42\/DBS\/000406"],"award-info":[{"award-number":["N42\/DBS\/000406"]}],"id":[{"id":"10.13039\/501100007088","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007088","name":"statutory funds from the Faculty of Pharmacy, Jagiellonian University Medical College, Cracow, Poland","doi-asserted-by":"publisher","award":["N42\/DBS\/000423"],"award-info":[{"award-number":["N42\/DBS\/000423"]}],"id":[{"id":"10.13039\/501100007088","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Vasorelaxant and antiplatelet agents play an important role in preventing and combating endothelial dysfunction, atherosclerosis and a plethora of associated cardiovascular diseases (CVDs). CVDs are the leading cause of death worldwide and nowadays occur not only in developed but also in developing societies. They include, among others, coronary heart disease, cerebrovascular disease and peripheral artery disease. Due to their high prevalence, it is important to seek efficient preventive measures, such as lifestyle changes and the implementation of appropriate herbal dietary supplementation and treatment alternatives. Plant-derived quinones have recently drawn researchers\u2019 attention due to their interesting biological potential. Embelin and rapanone are two plant-derived benzoquinones with anti-inflammatory and antioxidant properties. Embelin has already been shown to have vasorelaxant and antiplatelet activity, but little is known about rapanone in the context of CVDs. Therefore, we decided to comparatively evaluate their activity in a specially designed experimental protocol. Following the isolation of both benzoquinones from plant sources (rapanone from Ardisia crenata leaves; embelin from Lysimachia punctata roots), their effects were comparatively assessed in a biofunctional study on isolated rat aorta (precontracted with phenylephrine) and in vitro on platelet aggregation. Both benzoquinones showed 50% vasorelaxation in an NO-dependent manner. Interestingly, rapanone was slightly more effective as an antiplatelet agent than embelin. The antiplatelet effect of both benzoquinones was specific, as no cytotoxicity towards platelets was observed at the concentrations tested. This is the first report on the vasorelaxant and antiplatelet activity of rapanone.<\/jats:p>","DOI":"10.3390\/molecules30040845","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T12:12:16Z","timestamp":1739362336000},"page":"845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative Evaluation of Vasorelaxant and Antiplatelet Activity of Two Plant-Derived Benzoquinones: Rapanone and Embelin"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9780-7924","authenticated-orcid":false,"given":"Dagmara","family":"Wr\u00f3bel-Biedrawa","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4878-0723","authenticated-orcid":false,"given":"Monika","family":"Kubacka","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Medical College, Jagiellonian University, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3946-1192","authenticated-orcid":false,"given":"Magdalena","family":"Kota\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Screening, Medical College, Jagiellonian University, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Bednarski","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Screening, Medical College, Jagiellonian University, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1426-2218","authenticated-orcid":false,"given":"Karolina","family":"Grabowska","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-7192","authenticated-orcid":false,"given":"Irma","family":"Podolak","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1097\/01.ASN.0000132474.50966.DA","article-title":"Endothelial dysfunction","volume":"15","author":"Endemann","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_2","unstructured":"Lopez, E.O., Ballard, B.D., and Jan, A. (2024, September 03). Cardiovascular disease, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK535419\/."},{"key":"ref_3","unstructured":"(2024, September 02). World Health Organization. Available online: https:\/\/www.who.int\/health-topics\/cardiovascular-diseases#tab=tab_1."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1161\/HYPERTENSIONAHA.119.14240","article-title":"High blood pressure and cardiovascular disease","volume":"75","author":"Fuchs","year":"2020","journal-title":"Hypertension"},{"key":"ref_5","first-page":"49","article-title":"Koncepcja niestabilnej blaszki mia\u017cd\u017cycowej i farmakologiczne strategie terapeutyczne","volume":"17","author":"Sobczyk","year":"2015","journal-title":"Chir. Pol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrd1112","article-title":"Lovastatin and beyond: The history of the HMG-CoA reductase inhibitors","volume":"2","author":"Tobert","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"365","DOI":"10.32383\/farmpol\/116119","article-title":"Monakolina K\u2013naturalna statyna","volume":"75","author":"Malec","year":"2019","journal-title":"Farm. Pol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1097706","DOI":"10.1155\/2023\/1097706","article-title":"Therapeutic Role and Potential Mechanism of Resveratrol in Atherosclerosis: TLR4\/NF-\u03baB\/HIF-1\u03b1","volume":"2023","author":"Guo","year":"2023","journal-title":"Mediat. Inflamm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1080\/13880209.2016.1261905","article-title":"Effects of astaxanthin on blood coagulation, fibrinolysis and platelet aggregation in hyperlipidemic rats","volume":"55","author":"Deng","year":"2017","journal-title":"Pharmaceutic. Biol."},{"key":"ref_11","first-page":"161","article-title":"Evaluation of antioxidant, hypolipidemic, and antiatherogenic property of lycopene and astaxanthin in atherosclerosis-induced rats","volume":"9","author":"Kumar","year":"2017","journal-title":"Pharmacogn. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/med.21438","article-title":"Atheroprotective effects and molecular targets of tanshinones derived from herbal medicine danshen","volume":"38","author":"Fang","year":"2018","journal-title":"Med. Res. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chen, Z., Gao, X., Jiao, Y., Qiu, Y., Wang, A., Yu, M., Che, F., Li, S., Liu, J., and Li, J. (2019). Tanshinone IIA exerts anti-inflammatory and immune-regulating effects on vulnerable atherosclerotic plaque partially via the TLR4\/MyD88\/NF-\u03baB signal pathway. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00850"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4138","DOI":"10.2174\/0109298673268452231108061008","article-title":"Natural phenolic compounds with antithrombotic and antiplatelet effects: A drug-likeness approach","volume":"31","author":"Fernandes","year":"2024","journal-title":"Curr. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s10787-021-00816-9","article-title":"Quinone-rich fraction of Ardisia crispa (Thunb.) A. DC roots alters angiogenic cascade in collagen-induced arthritis","volume":"29","author":"Blin","year":"2021","journal-title":"Inflammopharmacology"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sharma, R., and Singh, S. (2024). A Review on Phytopharmacological Profile of Embelia ribes. Computational Optimization, Modeling, and Simulation for Engineering Applications, Apple Academic Press.","DOI":"10.1201\/9781003454021-5"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1080\/14786419.2021.1955361","article-title":"A comprehensive insight on the biological potential of embelin and its derivatives","volume":"36","author":"Basha","year":"2022","journal-title":"Nat. Prod. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/iub.2248","article-title":"Antiarthritic effect of chitosan nanoparticle loaded with embelin against adjuvant-induced arthritis in Wistar rats","volume":"72","author":"Cui","year":"2020","journal-title":"IUBMB Life"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104826","DOI":"10.1016\/j.tiv.2020.104826","article-title":"Anti-melanoma potential of two benzoquinone homologues embelin and rapanone-a comparative in vitro study","volume":"65","author":"Grabowska","year":"2020","journal-title":"Toxicol. In Vitro"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e14006","DOI":"10.1016\/j.heliyon.2023.e14006","article-title":"Embelin attenuates lipopolysaccharide-induced acute kidney injury through the inhibition of M1 macrophage activation and NF-\u03baB signaling in mice","volume":"9","author":"Tang","year":"2023","journal-title":"Heliyon"},{"key":"ref_21","first-page":"35","article-title":"Cardioprotective effect of aqueous extract of Embelia ribes Burm fruits against isoproterenol-induced myocardial infarction in albino rats","volume":"46","author":"Bhandari","year":"2008","journal-title":"Indian J. Exp. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Li, J.Y., Chen, R.J., Huang, L.T., Lee, T.Y., Lu, W.J., and Lin, K.H. (2019). Embelin as a novel inhibitor of PKC in the prevention of platelet activation and thrombus formation. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101724"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1055\/s-2001-18839","article-title":"Inhibition of acute and chronic inflammatory responses by the hydroxybenzoquinonic derivative rapanone","volume":"67","author":"Ospina","year":"2001","journal-title":"Planta Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wr\u00f3bel-Biedrawa, D., Galanty, A., Zagrodzki, P., and Podolak, I. (2022). Optimization of extraction conditions and cytotoxic activity of rapanone in comparison to its homologue, embelin. Molecules, 27.","DOI":"10.3390\/molecules27227912"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1365\/s10337-007-0511-4","article-title":"Qualitative and quantitative LC profile of embelin and rapanone in selected Lysimachia species","volume":"67","author":"Podolak","year":"2008","journal-title":"Chromatographia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1080\/14786419.2019.1614575","article-title":"Bioactive benzoquinones content variability in red-berry and white-berry varieties of Ardisia crenata Sims. and assessment of cytotoxic activity","volume":"35","author":"Podolak","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1055\/s-0031-1298379","article-title":"Preventive effect of embelin from Embelia ribes on lipid metabolism and oxidative stress in high-fat diet-induced obesity in rats","volume":"78","author":"Chaudhari","year":"2012","journal-title":"Planta Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.niox.2010.02.001","article-title":"Activation of endothelial nitric oxide synthase by the pro-apoptotic drug embelin: Striking discrepancy between nitric oxide-mediated cyclic GMP accumulation and L-citrulline formation","volume":"22","author":"Schmidt","year":"2010","journal-title":"Nitric Oxide"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1021\/tx970119u","article-title":"Inhibition of nitric oxide formation by neuronal nitric oxide synthase by quinones: Nitric oxide synthase as a quinone reductase","volume":"11","author":"Kumagai","year":"1998","journal-title":"Chem. Res. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s00204-005-0043-3","article-title":"Inhibition of endothelial nitric oxide synthase activity and suppression of endothelium-dependent vasorelaxation by 1, 2-naphthoquinone, a component of diesel exhaust particles","volume":"80","author":"Sun","year":"2006","journal-title":"Arch. Toxicol."},{"key":"ref_31","first-page":"543","article-title":"Inhibition of Angiogenesis and nitric oxide synthase (NOS), by embelin & vilangin using in vitro, in vivo & in silico studies","volume":"4","author":"Narayanaswamy","year":"2014","journal-title":"Adv. Pharm. Bull."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kundap, U.P., Bhuvanendran, S., Kumari, Y., Othman, I., and Shaikh, M.F. (2017). Plant derived phytocompound, embelin in CNS disorders: A systematic review. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00076"},{"key":"ref_33","first-page":"9682495","article-title":"Pharmacokinetic and bioavailability studies of embelin after intravenous and oral administration to rats","volume":"1","author":"Li","year":"2019","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ejphar.2011.04.037","article-title":"Embelin reduces cutaneous TNF-\u03b1 level and ameliorates skin edema in acute and chronic model of skin inflammation in mice","volume":"662","author":"Kumar","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.phymed.2013.03.003","article-title":"Anti-diabetic activity of embelin: Involvement of cellular inflammatory mediators, oxidative stress and other biomarkers","volume":"20","author":"Naik","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.bcp.2013.04.015","article-title":"Potent inhibition of human 5-lipoxygenase and microsomal prostaglandin E2 synthase-1 by the anti-carcinogenic and anti-inflammatory agent embelin","volume":"86","author":"Schaible","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.intimp.2011.01.022","article-title":"Embelin ameliorates dextran sodium sulfate-induced colitis in mice","volume":"11","author":"Kumar","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1248\/cpb.59.913","article-title":"Synthesis and evaluation of analgesic and anti-inflammatory activities of most active free radical scavenging derivatives of embelin\u2014A structure\u2013activity relationship","volume":"59","author":"Mahendran","year":"2011","journal-title":"Chem. Pharm. Bull."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ejphar.2010.12.012","article-title":"Protective effect of embelin against acetic acid induced ulcerative colitis in rats","volume":"654","author":"Thippeswamy","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jinorgbio.2017.02.019","article-title":"Discerning the antioxidant mechanism of rapanone: A naturally occurring benzoquinone with iron complexing and radical scavenging activities","volume":"170","author":"Antuch","year":"2017","journal-title":"J. Inorg. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.1021\/jo00247a030","article-title":"Structure of FR900359, a cyclic depsipeptide from Ardisia crenata Sims","volume":"53","author":"Fujioka","year":"1988","journal-title":"J. Org. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/s11418-012-0644-0","article-title":"Vasorelaxant effect of FR900359 from Ardisia crenata on rat aortic artery","volume":"67","author":"Zaima","year":"2013","journal-title":"J. Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.phrs.2019.01.012","article-title":"Anti-hypertensive mechanisms of cyclic depsipeptide inhibitor ligands for Gq\/11 class G proteins","volume":"141","author":"Meleka","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.fitote.2005.02.006","article-title":"Cytotoxic activity of embelin from Lysimachia punctata","volume":"76","author":"Podolak","year":"2005","journal-title":"Fitoterapia"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kubacka, M., Mogilski, S., Bednarski, M., Pociecha, K., \u015awierczek, A., Nicosia, N., Schabikowski, J., Za\u0142uski, M., Ch\u0142o\u0144-Rzepa, G., and Hockemeyer, J. (2023). Antiplatelet effects of selected xanthine-based adenosine A2A and A2B receptor antagonists determined in rat blood. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713378"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Trichler, S.A., Bulla, S.C., Thomason, J., Lunsford, K.V., and Bulla, C. (2013). Ultra-pure platelet isolation from canine whole blood. BMC Vet. Res., 9.","DOI":"10.1186\/1746-6148-9-144"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/0049-3848(89)90294-6","article-title":"Rapid Photometric method for estimation of platelet count in blood plasma or plasma suspension","volume":"56","author":"Walkowiak","year":"1989","journal-title":"Thrombosis Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/4\/845\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:31:54Z","timestamp":1760027514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/4\/845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,12]]},"references-count":48,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["molecules30040845"],"URL":"https:\/\/doi.org\/10.3390\/molecules30040845","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,12]]}}}