{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:13:52Z","timestamp":1773814432356,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,4,13]],"date-time":"2019-04-13T00:00:00Z","timestamp":1555113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004577","name":"Kementerian Pertanian dan Industri Asas Tani Malaysia","doi-asserted-by":"publisher","award":["NH0811S003"],"award-info":[{"award-number":["NH0811S003"]}],"id":[{"id":"10.13039\/501100004577","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Many Premna species have been used in traditional medicine to treat hypertension and cardiac insufficiency, and as a tonic for cardiac-related problems. Some have been reported to possess cardiovascular protective activity through several possible mechanisms, but not Premna foetida. In the present study, the methanol extract of P. foetida leaves (PFM) and its isolated compounds were evaluated for their ability to inhibit copper-mediated human low-density lipoprotein (LDL) oxidation and arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation. Six flavonoids, three triterpenoids, vanillic acid and stigmasterol were successfully isolated from PFM. Of the isolated compounds, quercetin was the most active against LDL oxidation (IC50 4.25 \u00b5M). The flavonols were more active than the flavones against LDL oxidation, suggesting that hydroxyl group at C-3 and the catechol moiety at B-ring may play important roles in protecting LDL from oxidation. Most tested flavonoids showed stronger inhibition towards AA-induced than the ADP-induced platelet aggregation with apigenin exhibiting the strongest effect (IC50 52.3 and 127.4 \u00b5M, respectively) while quercetin and kaempferol showed moderate activity. The results suggested that flavonoids, especially quercetin, apigenin and kaempferol were among the major constituents of P. foetida responsible for anti-LDL oxidation and anti-platelet aggregation.<\/jats:p>","DOI":"10.3390\/molecules24081469","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T11:15:58Z","timestamp":1555326958000},"page":"1469","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Inhibition of Human Platelet Aggregation and Low-Density Lipoprotein Oxidation by Premna foetida Extract and Its Major Compounds"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5767-209X","authenticated-orcid":false,"given":"Roza","family":"Dianita","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Pulau Pinang, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim","family":"Jantan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\u2019s University, Lakeside Campus, 47500 Subang Jaya, Selangor, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,13]]},"reference":[{"key":"ref_1","first-page":"141","article-title":"Bioactive foods and nutraceuticals supplementation criteria in cardiovascular protection","volume":"3","author":"Sharma","year":"2010","journal-title":"Open Nutraceuticals J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3390\/metabo2020303","article-title":"A historical overview of natural products in drug discovery","volume":"2","author":"Dias","year":"2012","journal-title":"Metabolites"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1084\/jem.20060218","article-title":"Lipoprotein oxidation in cardiovascular disease: Chief culprit or innocent bystander?","volume":"203","author":"Heinecke","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1161\/CIRCULATIONAHA.105.537878","article-title":"Pathophysiology of coronary artery disease","volume":"111","author":"Libby","year":"2005","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.phrs.2012.10.018","article-title":"Beneficial effects of polyphenols on cardiovascular disease","volume":"68","author":"Miguel","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S0944-7113(96)80081-X","article-title":"A review of the biological and pharmacological activities of saponins","volume":"2","author":"Wagner","year":"1996","journal-title":"Phytomedicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.2174\/092986712800229078","article-title":"Phytochemicals from plants to combat cardiovascular disease","volume":"19","author":"Vasanthi","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_8","unstructured":"Wiart, C. (2000). Medicinal Plants of Southeast Asia, Pelanduk Publication Sdn Bhd."},{"key":"ref_9","unstructured":"Perry, L.M., and Metzger, J. (1980). Medicinal Plants of East and Southeast Asia. Attributed properties and uses, The MIT Press."},{"key":"ref_10","unstructured":"Quattrocchi, U. (2012). CRC World Dictionary of Medicinal and Poisonous Plants, Vol. III (E-L), Taylor & Francis Group."},{"key":"ref_11","unstructured":"Burkill, I. (1966). A Dictionary of the Economic Products of the Malay Peninsula, Vol. II (I-Z)."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0378-8741(95)01343-1","article-title":"The ethnopharmacopoeia of the Rotuma","volume":"50","author":"McClatchey","year":"1996","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","first-page":"487","article-title":"Cardioprotective effect of ethanol extract of stem bark and stem wood of Premna serratifolia Lin. (Verbenaceae)","volume":"1","author":"Rajendran","year":"2008","journal-title":"Res. J. Pharm. Tech."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3329\/bjp.v3i2.952","article-title":"Cardiac stimulant activity of bark and wood of Premna serratifolia","volume":"3","author":"Rajendran","year":"2008","journal-title":"Bangladesh J. Pharmacol."},{"key":"ref_15","first-page":"20","article-title":"Evaluation of the cardioprotective effect of Premna mucronata Roxb (Verbenaceae) in the experimental model of myocardial ischemia-reperfusion injury","volume":"1","author":"Patel","year":"2012","journal-title":"Int. J. Modern. Pharm. Res."},{"key":"ref_16","first-page":"95","article-title":"Cardioprotective effect of flavonoids rich fraction of Premna mucronata on isoproterenol-induced myocardial infarction in Wistar rats","volume":"5","author":"Savsani","year":"2014","journal-title":"Int. J. Phytopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"M88","DOI":"10.3390\/M88","article-title":"2a,3b-Dihydroxyoleana-12-en-28-oic acid (maslinic acid)","volume":"3","author":"Martinez","year":"1998","journal-title":"Molecules"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1271\/bbb.67.2091","article-title":"Antimutagenic activity of flavonoids from Chrysanthemum morifolium","volume":"67","author":"Miyazawa","year":"2003","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/j.tiv.2008.08.007","article-title":"Anti-free radical activities of kaempferol isolated from Acacia nilotica (L.) Willd","volume":"22","author":"Singh","year":"2008","journal-title":"Ex. Del. Toxicol. In Vitro"},{"key":"ref_20","first-page":"234","article-title":"Phytochemical constituents of Bistorta manshuriensis","volume":"15","author":"Chang","year":"2009","journal-title":"Nat. Prod. Sci."},{"key":"ref_21","first-page":"11","article-title":"Antihepatotoxic activity and chemical constituents of Buddleja asiatica Lour","volume":"64c","author":"Wink","year":"2009","journal-title":"Z Naturforsch C"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Martins, D., Carrion, L.L., Ramos, D.F., Salom\u00e9, K.S., da Silva, P.E.A., Barison, A., and Nunez, V. (2013). Triterpenes and the antimycobacterial activity of Duroia macrophylla Huber (Rubiaceae). Biomed. Res. Int.","DOI":"10.1155\/2013\/605831"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"20962","DOI":"10.3390\/molecules191220962","article-title":"Aortic relaxant activity of Crataegus gracilior Phipps and identification of some of its chemical constituents","volume":"19","author":"Bah","year":"2014","journal-title":"Molecules"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wang, D., Yang, L., Zhou, D., and Zhang, J. (2014). Purification and characterization of flavonoids from the leaves of Zanthoxylum bungeanum and correlation between their structure and antioxidant activity. PLoS ONE.","DOI":"10.1371\/journal.pone.0105725"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1080\/13880209.2017.1323225","article-title":"Ethnomedicinal uses, phytochemistry, and pharmacological aspects of the genus Premna: A review","volume":"55","author":"Dianita","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16H","DOI":"10.1016\/0002-9149(86)90430-3","article-title":"Studies on the mechanism of action of probucol","volume":"57","author":"Steinberg","year":"1986","journal-title":"Am. J. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0891-5849(93)90510-2","article-title":"Probucol as an antioxidant and antiatherogenic drug","volume":"14","author":"Kuzuya","year":"1993","journal-title":"Free Radic Biol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1161\/01.ATV.9.4.462","article-title":"Mechanism of HDL reduction after probucol","volume":"9","author":"Franceschini","year":"1989","journal-title":"Arteriosclerosis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/S0022-2275(20)33877-3","article-title":"Effect of probucol on LDL oxidation and atherosclerosis in LDL receptor-deficient mice","volume":"39","author":"Bird","year":"1998","journal-title":"J. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1161\/01.ATV.21.4.594","article-title":"Measurement of copper-binding sites on low density lipoprotein","volume":"21","author":"Roland","year":"2001","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1093\/clinchem\/42.4.498","article-title":"Low-density lipoprotein oxidation, antioxidants, and atherosclerosis: A clinical biochemistry perspective","volume":"42","author":"Jialal","year":"1996","journal-title":"Clin. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9798","DOI":"10.1021\/jf0620719","article-title":"Distinctive antioxidant and antiinflammatory effects of flavonols","volume":"54","author":"Wang","year":"2006","journal-title":"J. Agric. Food. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0031-9422(02)00445-4","article-title":"Inhibition of LDL oxidation by flavonoids in relation to their structure and calculated enthalpy","volume":"62","author":"Vaya","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_34","first-page":"5895","article-title":"Function-structural study of anti-LDL-oxidation effects of flavonoid phytochemicals","volume":"6","author":"Yao","year":"2012","journal-title":"J. Med. Plant Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1152\/physrev.1989.69.1.58","article-title":"Molecular mechanisms of platelet activation","volume":"69","author":"Siess","year":"1989","journal-title":"Physiol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/FPC.0b013e3283406323","article-title":"Platelet aggregation pathway","volume":"21","author":"Sangkuhl","year":"2011","journal-title":"Pharmacogenet Genomics"},{"key":"ref_37","first-page":"76","article-title":"Antiplatelet effects of flavonoids mediated by inhibition of arachidonic acid-based pathway","volume":"82","author":"Hrdina","year":"2016","journal-title":"Planta Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jlumin.2015.07.037","article-title":"Spectroscopic study on flavonoid-drug interactions: Competitive binding for human serum albumin between three flavonoid compounds and ticagrelor, a new antiplatelet drug","volume":"168","author":"Liu","year":"2015","journal-title":"J. Lumin."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1007\/BF01965408","article-title":"Inhibition of aggregation and secretion of human platelets by quercetin and other flavonoids: Structure-activity relationships","volume":"12","author":"Beretz","year":"1982","journal-title":"Agents Actions"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"N1921","DOI":"10.1111\/1750-3841.12293","article-title":"Investigating flavonoids as molecular templates for the design of small molecule inhibitors of cell signaling","volume":"78","author":"Wright","year":"2013","journal-title":"J. Food Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1039\/c3fo60272a","article-title":"Flavonoid inhibitory pharmacodynamics on platelet function in physiological environment","volume":"4","author":"Wright","year":"2013","journal-title":"Food Funct."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2174\/1876506801205010013","article-title":"LDL as cause of atherosclerosis","volume":"5","author":"Tomkin","year":"2012","journal-title":"Open Atheroscler. Thromb. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3415","DOI":"10.1242\/jcs.01325","article-title":"Platelet adhesion signaling and the regulation of thrombus formation","volume":"117","author":"Gibbins","year":"2004","journal-title":"J. Cell. Sci."},{"key":"ref_44","unstructured":"ICH Harmonised Tripartite Guideline (2005). Validation of Analytical Procedures: Text and Methodology Q2-(R1), Step 4 Version, ICH."},{"key":"ref_45","first-page":"6182","article-title":"Effects of selected medicinal plants on human low-density lipoprotein oxidation, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and human platelet aggregation","volume":"5","author":"Saputri","year":"2011","journal-title":"J. Med. Plants Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/8\/1469\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:45:17Z","timestamp":1760186717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/8\/1469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,13]]},"references-count":45,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["molecules24081469"],"URL":"https:\/\/doi.org\/10.3390\/molecules24081469","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,13]]}}}