{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:07:24Z","timestamp":1789495644286,"version":"build-2803163510"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Antioxidants are compounds that inhibit, prevent, and reduce free radical activity caused by reactive oxygen species (ROS), thereby protecting cells from oxidative damage. Pomegranate (\n                    <jats:italic>Punica granatum<\/jats:italic>\n                    L.) is recognized as a valuable source of antioxidants, largely due to the phenolic and flavonoid compounds concentrated in its peel. Variations in cultivar, geographical region, and extraction methods are known to influence its bioactive composition. This study aimed to analyze the antioxidant capacity of the exocarp and mesocarp of three pomegranate varieties (red, yellow, and purple), grown in Indonesia, characterized by their different peel colors, extracted using ethanol (96%) and n-hexane, analyzed separately with total phenolic content (TPC), total flavonoid content (TFC), ABTS, and DPPH assays. The results showed variation in antioxidant capacity and biological compounds depending on both plant tissue and solvent used. Ethanolic extracts generally yielded higher phenolic and flavonoid contents, with the purple exocarp recording the highest TPC (721 mg GAE g\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) and TFC (161 mg QE g\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). In contrast, n-hexane extracts produce a lower yield, with the red mesocarp as the richest in bioactive compounds, with TPC (70.21 mg GAE g\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) and TFC (12.07 mg QE g\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). The ethanolic extracts consistently exhibited markedly stronger antioxidant activity, reflected by low IC\n                    <jats:sub>50<\/jats:sub>\n                    values in both ABTS and DPPH assays, with the purple pomegranate exocarp showing the highest potency (IC\n                    <jats:sub>50<\/jats:sub>\n                    value\u2009&lt;\u200950 \u03bcg mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), followed by the red and yellow varieties. In contrast, n-hexane extracts demonstrated substantially weaker activity, indicated by IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009&gt;\u2009200 ppm. Phytochemical profiling through LC-HRMS revealed the presence of diverse polar antioxidants, including phenolic acids, flavonoid glycosides, and anthocyanin derivatives, particularly abundant in the purple peel. Complementary GC-MS analysis confirmed the presence of non-polar constituents such as fatty acids, sterols, terpenoids, and other lipophilic metabolites. The antibacterial activity of the ethanolic peel extracts was evaluated against\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    and\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    using the broth microdilution method, revealing inhibitory effects across all varieties with IC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from 1417.41 to 5063.08 \u00b5g mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    . The ethanolic extract of yellow pomegranate mesocarp exhibited the strongest antibacterial activity, while the ethanolic extract of yellow pomegranate exocarp showed the weakest inhibition. In the MTT assay, all ethanolic extracts of pomegranate peel from three varieties demonstrated antiproliferative effects against Huh7it cells after 48 h incubation. Notably, the purple pomegranate exocarp showed the highest cytotoxic potency (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u2009231.22 \u00b5g mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). This research can be used as initial information about new sources of antioxidants.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0357371","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T17:43:57Z","timestamp":1789494237000},"page":"e0357371","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative phytochemical profiling and bioactivity evaluation of three Indonesian pomegranate (Punica granatum) peel varieties: Antioxidant, antibacterial, and in vitro antiproliferative activities"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8414-1438","authenticated-orcid":true,"given":"Triono Bagus","family":"Saputro","sequence":"first","affiliation":[{"name":"Institut Teknologi Sepuluh Nopember","place":["Surabaya, Jawa Timur, Indonesia"],"department":["Department of Biology, Faculty of Science and Data Analytics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aulia Sunan","family":"Fadilah","sequence":"additional","affiliation":[{"name":"Institut Teknologi Sepuluh Nopember","place":["Surabaya, Jawa Timur, Indonesia"],"department":["Department of Biology, Faculty of Science and Data Analytics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisatus","family":"Solihah","sequence":"additional","affiliation":[{"name":"Institut Teknologi Sepuluh Nopember","place":["Surabaya, Jawa Timur, Indonesia"],"department":["Department of Biology, Faculty of Science and Data Analytics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awik Puji Dyah","family":"Nurhayati","sequence":"additional","affiliation":[{"name":"Institut Teknologi Sepuluh Nopember","place":["Surabaya, Jawa Timur, Indonesia"],"department":["Department of Biology, Faculty of Science and Data Analytics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panita","family":"Chutimanukul","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency","place":["Khlong Luang, Pathum Thani, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamdan Dwi","family":"Rizqi","sequence":"additional","affiliation":[{"name":"Institut Teknologi Sepuluh Nopember","place":["Surabaya, Jawa Timur, Indonesia"],"department":["Department of Chemistry, Faculty of Science and Data Analytics"]},{"name":"University Teknologi Malaysia","place":["Johor, Malaysia"],"department":["Advanced Membrane Technology Research Centre (AMTEC), Faculty of Chemical and Energy Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"pone.0357371.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2024\/5594386","article-title":"A comprehensive review of free radicals, oxidative stress, and antioxidants: overview, clinical applications, global perspectives, future directions, and mechanisms of antioxidant activity of flavonoid compounds","volume":"2024","author":"SG Tumilaar","year":"2024","journal-title":"J Chem"},{"issue":"4","key":"pone.0357371.ref002","first-page":"106","article-title":"Phytochemical screening and antioxidant activity of pomegranate peel and leaves of peach","volume":"8","author":"SM Elmezwghy","year":"2020","journal-title":"Int J Herb Med"},{"issue":"2","key":"pone.0357371.ref003","doi-asserted-by":"crossref","first-page":"83","DOI":"10.5455\/oams.010413.rv.005","article-title":"Effects of free radicals and antioxidants on exercise performance","volume":"2","author":"S Lamina","year":"2013","journal-title":"Oxid Antioxid Med Sci"},{"issue":"01","key":"pone.0357371.ref004","doi-asserted-by":"crossref","first-page":"4","DOI":"10.47310\/iarjimph.2023.v04i01.016","article-title":"Oxidative stress, antioxidants and biomarkers: appreciation for analytical methods for health promotion","volume":"04","author":"AF Finha","year":"2023","journal-title":"Int Acad Res J Intern Med Public Health"},{"issue":"2","key":"pone.0357371.ref005","first-page":"353","article-title":"Antioxidants from natural sources: review","volume":"3","author":"SR Jaiswal","year":"2023","journal-title":"Int J Human Soc Sci Manage"},{"issue":"11","key":"pone.0357371.ref006","first-page":"2790","article-title":"A review of antioxidants from natural sources","volume":"4","author":"NN Kamble","year":"2023","journal-title":"Int J Res Public Rev"},{"key":"pone.0357371.ref007","first-page":"1","article-title":"Antioxidant metabolism pathways in vitamins, polyphenols, and selenium: parallels and divergences","volume":"25","author":"CMC Andr\u00e9s","year":"2024","journal-title":"Int J Mol Sci"},{"key":"pone.0357371.ref008","unstructured":"IMARC. Form (Dry, Liquid), Application (Food and Feed Additives, Pharmaceuticals and Personal Care Products, Fuel and Lubricant Additives, Plastic, Rubber, and Latex Additives and Antioxidants Market Report by Type (Natural Antioxidants, Synthetic Antioxidants). 2023;26."},{"issue":"1825","key":"pone.0357371.ref009","first-page":"1","article-title":"Advances in natural antioxidants for food improvement","volume":"11","author":"M L\u00f3pez-Pedrouso","year":"2022","journal-title":"Antioxidants"},{"key":"pone.0357371.ref010","doi-asserted-by":"crossref","first-page":"108613","DOI":"10.1016\/j.envint.2024.108613","article-title":"The hidden diet: synthetic antioxidants in packaged food and their impact on human exposure and health","volume":"186","author":"X Ji","year":"2024","journal-title":"Environ Int"},{"issue":"762","key":"pone.0357371.ref011","first-page":"1","article-title":"Agro-industrial by-products of plant origin: therapeutic uses as well as antimicrobial and antioxidant activity","volume":"14","author":"Y Enciso-Mart\u00ednez","year":"2024","journal-title":"Biomolecules"},{"key":"pone.0357371.ref012","doi-asserted-by":"crossref","first-page":"35452","DOI":"10.1021\/acsomega.3c02586","article-title":"Pomegranate peel phytochemistry, pharmacological properties, methods of extraction, and its application: a comprehensive review","volume":"8","author":"J Singh","year":"2023","journal-title":"ACS Omega"},{"key":"pone.0357371.ref013","first-page":"1","article-title":"The whole pomegranate (Punica granatum. L), biological properties and important findings: a review","volume":"2","author":"AG Valero-Mendoza","year":"2023","journal-title":"Food Chem Adv"},{"key":"pone.0357371.ref014","first-page":"1","article-title":"An overview of the health benefits, extraction methods and improving the properties of pomegranate","volume":"12","author":"G Benedetti","journal-title":"Antioxidants"},{"key":"pone.0357371.ref015","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.indcrop.2018.01.031","article-title":"Activity guided fractionation of pomegranate extract and its antioxidant, antidiabetic and anti-neurodegenerative properties","volume":"113","author":"K \u0160avikin","year":"2018","journal-title":"Ind Crops Prod"},{"key":"pone.0357371.ref016","doi-asserted-by":"crossref","first-page":"1265018","DOI":"10.3389\/fpls.2023.1265018","article-title":"Comparative analysis of the phenolic contents and antioxidant activities of different parts of two pomegranate (Punica granatum L.) Cultivars: \u201cTunisia\u201d and \u201cQingpi\u201d","volume":"14","author":"H Zhang","year":"2023","journal-title":"Front Plant Sci"},{"issue":"2","key":"pone.0357371.ref017","first-page":"6","article-title":"Karakterisasi anatomi delima (Punica granatum L)","volume":"9","author":"V Andriani","year":"2016","journal-title":"Stigma J Sci"},{"issue":"2","key":"pone.0357371.ref018","doi-asserted-by":"crossref","DOI":"10.22219\/farmasains.v5i2.13472","article-title":"Studies on antioxidant activity of red, yellow, and black pomegranate (Punica granatum L.) peel extract using DPPH radical scavenging method","volume":"5","author":"U Chasanah","year":"2020","journal-title":"Farmasains: Jurnal Ilmu Farmasi dan Kesehatan"},{"key":"pone.0357371.ref019","article-title":"Karakterisasi anatomi dan aktivitas antioksidan delima (Punica granatum L.)","author":"Suharyanto","year":"2015","journal-title":"Yogyakarta"},{"issue":"5","key":"pone.0357371.ref020","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3390\/horticulturae8050384","article-title":"Evaluation of morphological, qualitative, and metabolomic traits during fruit ripening in pomegranate (Punica granatum L.)","volume":"8","author":"A Cirillo","year":"2022","journal-title":"Horticulturae"},{"issue":"4","key":"pone.0357371.ref021","first-page":"1","article-title":"Fourier-transform infrared spectroscopy, antioxidant, phytochemical and antibacterial screening of n-hexane extracts of Punica granatum","volume":"19","author":"M Sharif","year":"2020","journal-title":"Genet Mol Res"},{"key":"pone.0357371.ref022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2023\/8860476","article-title":"Application of pomegranate peel extract, a waste agricultural product, as a natural preservative in Tahini","volume":"2023","author":"R Ghasemi","year":"2023","journal-title":"Int J Food Sci"},{"issue":"1","key":"pone.0357371.ref023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/jpbs.JPBS_175_19","article-title":"Preparation of medicinal plants: basic extraction and fractionation procedures for experimental purposes","volume":"12","author":"AR Abubakar","year":"2020","journal-title":"J Pharm Bioallied Sci"},{"issue":"2","key":"pone.0357371.ref024","doi-asserted-by":"crossref","first-page":"97","DOI":"10.15575\/ijhar.v4i2.17188","article-title":"The effect of extraction method on the extract yield in the carotenoid pigment encapsulation for halal natural pigment","volume":"4","author":"I Fajriati","year":"2022","journal-title":"Indonesian J Halal Res"},{"issue":"1","key":"pone.0357371.ref025","doi-asserted-by":"crossref","first-page":"012019","DOI":"10.1088\/1755-1315\/800\/1\/012019","article-title":"Antioxidant of n-hexane, ethyl acetate and methanol extracts of Padina sp with DPPH method","volume":"800","author":"A Akbar","year":"2021","journal-title":"IOP Conf Ser: Earth Environ Sci"},{"issue":"2","key":"pone.0357371.ref026","doi-asserted-by":"crossref","first-page":"123","DOI":"10.15294\/ijcs.v11i2.54610","article-title":"Determination of total phenolic, total flavonoid, and antioxidant activity of india onion extract","volume":"11","author":"LA Hidayah","year":"2022","journal-title":"Indonesian J Chem Sci"},{"issue":"5","key":"pone.0357371.ref027","first-page":"2062","article-title":"Antioxidant activity screening of seven Indonesian herbal extract","volume":"21","author":"J Sukweenadhi","year":"2020","journal-title":"Biodiversitas"},{"issue":"1","key":"pone.0357371.ref028","first-page":"600","article-title":"Colorimetric Method For Total Phenolic and Flavonoid Content Determination Of Fig (Ficus Carica L.) Leaves Extract From West Java","author":"NM Saptarini","year":"2022","journal-title":"Indonesia Rasayan J Chem"},{"issue":"96","key":"pone.0357371.ref029","first-page":"1","article-title":"Total phenolic content, flavonoid content and antioxidant potential of wild vegetables from western nepal","volume":"8","author":"S Aryal","year":"2019","journal-title":"Plants"},{"issue":"7","key":"pone.0357371.ref030","doi-asserted-by":"crossref","first-page":"3380","DOI":"10.3390\/ijms22073380","article-title":"Analytical methods used in determining antioxidant activity: a review","volume":"22","author":"IG Munteanu","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"12","key":"pone.0357371.ref031","first-page":"1572","article-title":"Analisis aktivitas antioksidan pada sediaan masker wajah kulit buah delima merah (Punica granatum L.) melalui reaksi antara ekstraknya dengan 1,1-diphenyl-2-picrylhydrazyl (DPPH) dan","volume":"1","author":"Arsyad","year":"2021","journal-title":"Sosains"},{"issue":"1","key":"pone.0357371.ref032","doi-asserted-by":"crossref","first-page":"35","DOI":"10.21776\/ub.jtp.2023.024.01.4","article-title":"Perbandingan berbagai metode pengujian aktivitas antioksidan (DPPH, ABTS dan FRAP) pada teh hitam (Camellia sinensis)","volume":"24","author":"Z Theafelicia","year":"2023","journal-title":"Jurnal Teknologi Pertanian"},{"issue":"12","key":"pone.0357371.ref033","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.3390\/plants10122742","article-title":"In Vitro Evaluation of Biological Activities and Phytochemical Analysis of Different Solvent Extracts of Punica granatum L. (Pomegranate) Peel","volume":"10","author":"MT Yassin","year":"2021","journal-title":"Plants"},{"key":"pone.0357371.ref034","volume-title":"Rahasia kesehatan dengan delima","author":"Vee","year":"2023","edition":"1"},{"issue":"10","key":"pone.0357371.ref035","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.3390\/antiox10101530","article-title":"Correlation study of antioxidant activity with phenolic and flavonoid compounds in 12 Indonesian Indigenous Herbs","volume":"10","author":"YM Muflihah","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"pone.0357371.ref036","first-page":"32","article-title":"In vitro antibacterial activity of selected medicinal plants traditionally used in Vietnam against human pathogenic bacteria","volume":"16","author":"TT Vu","year":"2016","journal-title":"BMC Complement Altern Med"},{"issue":"1265018","key":"pone.0357371.ref037","first-page":"1","article-title":"Comparative analysis of the phenolic contents and antioxidant activities of different parts of two pomegranate (Punica granatum L.) cultivars: \u2018Tunisia\u2019 and \u2018Qingpi\u2019","volume":"14","author":"H Zhang","year":"2023","journal-title":"Front Plant Sci"},{"issue":"1322450","key":"pone.0357371.ref038","first-page":"1","article-title":"Discovering the anti-diabetic potential of pomegranate peel metabolites by examining molecular interplay with the thioredoxin interacting protein","volume":"10","author":"T Aslam","year":"2024","journal-title":"Front Med"},{"issue":"2","key":"pone.0357371.ref039","doi-asserted-by":"crossref","first-page":"14","DOI":"10.22270\/ajprd.v8i2.710","article-title":"Antimicrobial and antioxidant activity of pomegranate peel extracts obtained by sequential extraction method","volume":"8","author":"MMS Abdealsiede","year":"2020","journal-title":"Asian J Pharmaceut Res Dev"},{"issue":"11","key":"pone.0357371.ref040","first-page":"2521","article-title":"Analysis of the phytochemical composition of pomegranate fruit juices, peels and kernels: a comparative study on four cultivars grown in Southern Italy","volume":"10","author":"A Montefusco","year":"2021","journal-title":"Plants (Basel)"},{"issue":"1","key":"pone.0357371.ref041","first-page":"28","article-title":"Ekstraksi Senyawa BIoaktif sebagai Antioksidan Alami Spirulina Platensis Segar dengan Pelarut yang Berbeda","volume":"18","author":"F Firdayani","year":"2015","journal-title":"J. Pengolah Has Perikan Indones"},{"issue":"2","key":"pone.0357371.ref042","doi-asserted-by":"crossref","first-page":"103553","DOI":"10.1016\/j.sjbs.2022.103553","article-title":"Potential of phenolic compounds from pomegranate (Punica granatum L.) by-product with significant antioxidant and therapeutic effects: A narrative review","volume":"30","author":"AA Saparbekova","year":"2023","journal-title":"Saudi J Biol Sci"},{"key":"pone.0357371.ref043","doi-asserted-by":"crossref","first-page":"6584","DOI":"10.1021\/acs.jafc.6b02950","article-title":"Phenolic compounds of pomegranate byproducts (Outer Skin, Mesocarp, Divider Membrane) and their antioxidant activities","volume":"64","author":"P Ambigaipalan","year":"2016","journal-title":"J Agric Food Chem"},{"issue":"2","key":"pone.0357371.ref044","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.3390\/ijms24021002","article-title":"Transcriptome and physio-biochemical profiling reveals differential responses of rice cultivars at reproductive-stage drought stress","volume":"24","author":"S Kaur","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"3","key":"pone.0357371.ref045","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/jsfa.7799","article-title":"Antimicrobial activity of pomegranate peel extracts as affected by cultivar","volume":"97","author":"EC Rosas\u2010Burgos","year":"2016","journal-title":"J Sci Food Agric"},{"issue":"20","key":"pone.0357371.ref046","doi-asserted-by":"crossref","first-page":"9427","DOI":"10.1021\/jf901880p","article-title":"Antioxidant capacity and lipid characterization of six Georgia-grown pomegranate cultivars","volume":"57","author":"G Pande","year":"2009","journal-title":"J Agric Food Chem"},{"key":"pone.0357371.ref047","article-title":"A comprehensive review on medicinal plant extracts as antibacterial agents: factors, mechanism insights and future prospects","volume":"26","author":"N Zouine","year":"2024","journal-title":"Sci Afr"},{"issue":"1","key":"pone.0357371.ref048","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s13280-021-01561-7","article-title":"Recognizing Indigenous peoples and local communities rights and agency in the post-2020 Biodiversity Agenda","volume":"51","author":"V Reyes-Garc\u00eda","year":"2022","journal-title":"Ambio"},{"issue":"1","key":"pone.0357371.ref049","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s43141-021-00151-0","article-title":"Chemical profiling, in vitro antimicrobial and antioxidant activities of pomegranate, orange and banana peel-extracts against pathogenic microorganisms","volume":"19","author":"SM Hanafy","year":"2021","journal-title":"J Genet Eng Biotechnol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0357371","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T17:44:14Z","timestamp":1789494254000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0357371"}},"subtitle":[],"editor":[{"given":"Shengwei","family":"Sun","sequence":"first","affiliation":[{"name":"KTH Royal Institute of Technology","place":["SWEDEN"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":49,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0357371","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}