Chemical Composition of the Phenolic Profile and Evaluation of Antimicrobial and Cytotoxic Activities of Moroccan Pomegranate (Punica granatum) Peel Extract

Chemical Composition of the Phenolic Profile and Evaluation of Antimicrobial and Cytotoxic Activities of Moroccan Pomegranate (Punica granatum) Peel Extract | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Chemical Composition of the Phenolic Profile and Evaluation of Antimicrobial and Cytotoxic Activities of Moroccan Pomegranate (Punica granatum) Peel Extract Fahd KANDSI, Kaouthar EL BIRGUI, Mohamed EL FADILI, Mohammed AL-ZHARANI, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6983468/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract This study aims to deepen the understanding of the pharmacological properties of the aqueous extract derived from the peel of Punica granatum L., sourced from eastern Morocco. Chemical analysis using ultra-high-performance liquid chromatography (UHPLC) led to the identification of 30 compounds, mainly phenolic acids and flavonoids. The major constituents were quercetin (23.32%), gallic acid (12.85%), caffeic acid (12.44%), and hesperetin (12.11%). The antimicrobial activity of the extract was evaluated using the broth microdilution method, revealing strong efficacy against Gram-positive bacteria, particularly Bacillus cereus (MIC = 0.781 mg/mL) and Staphylococcus aureus (MIC = 1.56 mg/mL), while Escherichia coli exhibited higher resistance (MIC = 3.125 mg/mL). Cytotoxicity assessment showed greater inhibition of splenocytes (IC 50 = 708.7 ± 49.46 µg/mL) compared to myeloma P3 cell lines (IC 50 = 950.3 ± 43.8 µg/mL), suggesting potential selectivity. An in silico study was conducted to explore the pharmacokinetic and toxicological properties of the main compounds. Hesperetin and gallic acid were predicted to be non-toxic and exhibited strong binding affinities to antibacterial target proteins and to BCL-2, a key regulator of apoptosis. Hesperetin demonstrated more stable and diverse interactions with BCL-2, indicating superior potential as an inhibitor. These findings suggest that pomegranate peel extract may serve as a promising source of bioactive compounds for the development of new antimicrobial and anticancer agents. Biological sciences/Biochemistry Biological sciences/Biotechnology Biological sciences/Drug discovery Biological sciences/Microbiology Biological sciences/Plant sciences Punica granatum UHPLC antimicrobial activity cytotoxicity and natural bioactives Full Text Additional Declarations No competing interests reported. Supplementary Files UHPCchromatogramsPGE.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6983468","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":487899064,"identity":"43c99d38-b0ba-44da-9c69-e485d0731251","order_by":0,"name":"Fahd KANDSI","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYBACCTA2YOAHkoYPSNIi2SDBYGxAghYGsBYzCaK0SLafPXjzRwGDBP/s5m3VvDl3GPjbD7Bu+IFHizRPXrI1jwGDhMSdY2W3ebc9Y5A4k8B2swePFjmGHDNpoF/qGG7kmAG1HGZguMHAdoMHnxb+N2aSP4C2yAO1FIO0yAO13PyDz2ESOWYSIIcZALUwg7QYALXcxmeL5Iw3xkC/SEgY3kgrlpy77RmP4ZnEttsyeLRInM8xvPnjj42E3I3kjR/ebrsjJ3f88LGbb/BogemEMQ4AncTYQFgDEjhAkupRMApGwSgYGQAAEMtJJFpx2RYAAAAASUVORK5CYII=","orcid":"","institution":"Mohammed First University","correspondingAuthor":true,"prefix":"","firstName":"Fahd","middleName":"","lastName":"KANDSI","suffix":""},{"id":487899065,"identity":"f2536192-b302-45b5-a689-4cbb5cdab562","order_by":1,"name":"Kaouthar EL BIRGUI","email":"","orcid":"","institution":"Hassan II University of Casablanca","correspondingAuthor":false,"prefix":"","firstName":"Kaouthar","middleName":"EL","lastName":"BIRGUI","suffix":""},{"id":487899066,"identity":"b958a18e-0f1f-4866-b080-6e119232185a","order_by":2,"name":"Mohamed EL FADILI","email":"","orcid":"","institution":"Sidi Mohammed Ben Abdellah University","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"EL","lastName":"FADILI","suffix":""},{"id":487899067,"identity":"de774f6b-773a-41c0-917a-067ecc90acd8","order_by":3,"name":"Mohammed AL-ZHARANI","email":"","orcid":"","institution":"Imam Mohammad Ibn Saud Islamic University (IMSIU)","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"","lastName":"AL-ZHARANI","suffix":""},{"id":487899068,"identity":"7a8a1e82-f2a9-4509-97a4-05a7322707e9","order_by":4,"name":"Chaimaa SABIRI","email":"","orcid":"","institution":"Hassan II University of Casablanca","correspondingAuthor":false,"prefix":"","firstName":"Chaimaa","middleName":"","lastName":"SABIRI","suffix":""},{"id":487899069,"identity":"da7fe788-440f-4ef5-9836-49b60902935a","order_by":5,"name":"Othman EL FAQER","email":"","orcid":"","institution":"Hassan II University","correspondingAuthor":false,"prefix":"","firstName":"Othman","middleName":"EL","lastName":"FAQER","suffix":""},{"id":487899070,"identity":"24a140d4-4a09-4d59-afd3-aa5823444a97","order_by":6,"name":"Raffaele CONTE","email":"","orcid":"","institution":"Research Institute on Terrestrial Ecosystems (IRET)-CNR","correspondingAuthor":false,"prefix":"","firstName":"Raffaele","middleName":"","lastName":"CONTE","suffix":""},{"id":487899071,"identity":"4852f7fb-7e65-47c5-b8de-13748fa2e10b","order_by":7,"name":"Mohamed BOUHRIM","email":"","orcid":"","institution":"Faculty of Pharmaceutical and Biological Sciences, Lille, France","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"","lastName":"BOUHRIM","suffix":""},{"id":487899072,"identity":"495ea81d-34f6-480d-b417-fee368e8bf27","order_by":8,"name":"Fahd A. 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Chemical analysis using ultra-high-performance liquid chromatography (UHPLC) led to the identification of 30 compounds, mainly phenolic acids and flavonoids. The major constituents were quercetin (23.32%), gallic acid (12.85%), caffeic acid (12.44%), and hesperetin (12.11%). The antimicrobial activity of the extract was evaluated using the broth microdilution method, revealing strong efficacy against Gram-positive bacteria, particularly \u003cem\u003eBacillus cereus\u003c/em\u003e (MIC\u0026thinsp;=\u0026thinsp;0.781 mg/mL) and \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MIC\u0026thinsp;=\u0026thinsp;1.56 mg/mL), while \u003cem\u003eEscherichia coli\u003c/em\u003e exhibited higher resistance (MIC\u0026thinsp;=\u0026thinsp;3.125 mg/mL). Cytotoxicity assessment showed greater inhibition of splenocytes (IC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;708.7\u0026thinsp;\u0026plusmn;\u0026thinsp;49.46 \u0026micro;g/mL) compared to myeloma P3 cell lines (IC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;950.3\u0026thinsp;\u0026plusmn;\u0026thinsp;43.8 \u0026micro;g/mL), suggesting potential selectivity. An \u003cem\u003ein silico\u003c/em\u003e study was conducted to explore the pharmacokinetic and toxicological properties of the main compounds. Hesperetin and gallic acid were predicted to be non-toxic and exhibited strong binding affinities to antibacterial target proteins and to BCL-2, a key regulator of apoptosis. Hesperetin demonstrated more stable and diverse interactions with BCL-2, indicating superior potential as an inhibitor. These findings suggest that pomegranate peel extract may serve as a promising source of bioactive compounds for the development of new antimicrobial and anticancer agents.\u003c/p\u003e","manuscriptTitle":"Chemical Composition of the Phenolic Profile and Evaluation of Antimicrobial and Cytotoxic Activities of Moroccan Pomegranate (Punica granatum) Peel Extract","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-21 13:44:24","doi":"10.21203/rs.3.rs-6983468/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"afa0da3e-b4a6-4f49-a7f9-955b0cbd7cd1","owner":[],"postedDate":"July 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51797303,"name":"Biological sciences/Biochemistry"},{"id":51797304,"name":"Biological sciences/Biotechnology"},{"id":51797305,"name":"Biological sciences/Drug discovery"},{"id":51797306,"name":"Biological sciences/Microbiology"},{"id":51797307,"name":"Biological sciences/Plant sciences"}],"tags":[],"updatedAt":"2025-10-09T05:39:05+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-21 13:44:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6983468","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6983468","identity":"rs-6983468","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}