{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:20:34Z","timestamp":1784863234125,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Health Sciences, Scientific Research Projects Coordination Unit","award":["2024\/032"],"award-info":[{"award-number":["2024\/032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study aimed to evaluate the inhibitory potential of phenolic-rich extracts from selected medicinal plants belonging to the Lamiaceae and Asteraceae families against the furin protease enzyme, a key target in viral and oncogenic pathways. Extracts of Origanum vulgare, Thymus vulgaris, Mentha piperita, Mentha spicata, Salvia officinalis, and Silybum marianum were prepared using hexane, chloroform, and ethyl acetate. Phenolic compounds were quantified using High-Performance Liquid Chromatography (HPLC). Furin inhibition was assessed spectrophotometrically and analyzed statistically with multivariate approaches. The chloroform extract of Origanum vulgare exhibited 97.44 \u00b1 0.12% inhibition, while the ethyl acetate extract of Mentha spicata showed 97.44 \u00b1 0.08% inhibition. Epicatechin and rutin displayed significant synergistic effects, while naringenin negatively affected inhibition (p &lt; 0.05). Solvent polarity significantly influenced phenolic diversity and biological activity, with ternary combinations showing 33% higher inhibition than single compounds. These findings highlight phenolic blends as promising natural furin inhibitors, with chloroform being optimal for broad-spectrum extraction.<\/jats:p>","DOI":"10.3390\/molecules30173450","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T07:41:45Z","timestamp":1755848505000},"page":"3450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synergistic Phenolic Compounds in Medicinal Plant Extracts: Enhanced Furin Protease Inhibition via Solvent-Specific Extraction from Lamiaceae and Asteraceae Families"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-4952","authenticated-orcid":false,"given":"Fatime Bet\u00fcl","family":"\u00dczer","sequence":"first","affiliation":[{"name":"Department of Phytotherapy, University of Health Sciences, Selimiye Complex, Selimiye Neighborhood, Atolyeler Street No: 4, Uskudar, 34668 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7496-1208","authenticated-orcid":false,"given":"Nazl\u0131","family":"Helvac\u0131","sequence":"additional","affiliation":[{"name":"Department of Phytotherapy, University of Health Sciences, Selimiye Complex, Selimiye Neighborhood, Atolyeler Street No: 4, Uskudar, 34668 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1502-1141","authenticated-orcid":false,"given":"Mahfuz","family":"Elmasta\u015f","sequence":"additional","affiliation":[{"name":"Department of Phytotherapy, University of Health Sciences, Selimiye Complex, Selimiye Neighborhood, Atolyeler Street No: 4, Uskudar, 34668 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/joim.12783","article-title":"Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality","volume":"284","author":"Fernandez","year":"2018","journal-title":"J. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1152\/physrev.00013.2020","article-title":"Elevated plasmin(ogen) as a common risk factor for COVID-19 susceptibility","volume":"100","author":"Ji","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1021\/jm400460d","article-title":"Chikungunya Virus: Emerging Targets and New Opportunities for Medicinal Chemistry","volume":"57","author":"Rashad","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"621","DOI":"10.2217\/fvl.09.56","article-title":"Ebolavirus glycoprotein structure and mechanism of entry","volume":"4","author":"Lee","year":"2009","journal-title":"Future Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"31642","DOI":"10.1074\/jbc.M102633200","article-title":"Proteolytic Activation of Respiratory Syncytial Virus Fusion Protein","volume":"276","author":"Zimmer","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1002\/j.1460-2075.1992.tb05305.x","article-title":"Influenza virus hemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease","volume":"11","author":"Vey","year":"1992","journal-title":"EMBO J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/10409230802058320","article-title":"Structures and Mechanisms of Viral Membrane Fusion Proteins: Multiple Variations on a Common Theme","volume":"43","author":"White","year":"2008","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/1475-2875-9-264","article-title":"Potential threat of malaria epidemics in a low transmission area, as exemplified by S\u00e3o Tom\u00e9 and Pr\u00edncipe","volume":"9","author":"Lee","year":"2010","journal-title":"Malar. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.biochem.69.1.531","article-title":"Receptor Binding and Membrane Fusion in Virus Entry: The Influenza Hemagglutinin","volume":"69","author":"Skehel","year":"2000","journal-title":"Annu. Rev. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/978-94-007-6552-8_16","article-title":"Entry of Enveloped Viruses into Host Cells: Membrane Fusion","volume":"68","author":"Melero","year":"2013","journal-title":"Subcell Biochem."},{"key":"ref_11","unstructured":"Ivanova, T.P. (2017). Beitr\u00e4ge zur Inhibierung der Proproteinkonvertase Furin. [Ph.D. Thesis, Universit\u00e4t Bielefeld]."},{"key":"ref_12","first-page":"11","article-title":"The factor VIII protein and its function","volume":"63","author":"Ciach","year":"2016","journal-title":"Acta Biochim. Pol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1073","DOI":"10.1002\/cti2.1073","article-title":"Furin-mediated protein processing in infectious diseases and cancer","volume":"8","author":"Braun","year":"2019","journal-title":"Clin. Transl. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e00128-22","DOI":"10.1128\/jvi.00128-22","article-title":"Distinctive Roles of Furin and TMPRSS2 in SARS-CoV-2 Infectivity","volume":"96","author":"Essalmani","year":"2022","journal-title":"J. Virol."},{"key":"ref_15","first-page":"12565","article-title":"Predictions of Some Methyl \u03b2-D-Galactopyranoside Analogs","volume":"11","author":"Amin","year":"2021","journal-title":"Biointerface Res. Appl. Chem."},{"key":"ref_16","unstructured":"Jaaks, P.A.I.M. (2016). The Proprotein Convertase Furin is a Key Regulator of Paediatric Sarcoma Malignancy. [Ph.D. Thesis, University of Cambridge]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/ptr.6843","article-title":"Aframomum melegueta secondary metabolites exhibit polypharmacology against SARS-CoV-2 drug targets: In vitro validation of furin inhibition","volume":"35","author":"Omotuyi","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/s43094-021-00348-7","article-title":"Computational guided identification of potential leads from Acacia pennata (L.) Willd. as inhibitors for cellular entry and viral replication of SARS-CoV-2","volume":"7","author":"Zothantluanga","year":"2021","journal-title":"Futur. J. Pharm. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11467","DOI":"10.1080\/07391102.2021.1959401","article-title":"Polypharmacology of some medicinal plant metabolites against SARS-CoV-2 and host targets: Molecular dynamics evaluation of NSP9 RNA binding protein","volume":"40","author":"Bandyopadhyay","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lakhani, K.G., Hamid, R., Gupta, S., Prajapati, P., Prabha, R., and Patel, S. (2024). Exploring the therapeutic mechanisms of millet in obesity through molecular docking, pharmacokinetics, and dynamic simulation. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1453819"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1556\/1886.2021.00022","article-title":"Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants","volume":"11","author":"Goc","year":"2022","journal-title":"Eur. J. Microbiol. Immunol."},{"key":"ref_22","first-page":"67","article-title":"Ethnobotany, Phytochemistry, Pharmacology and Nutritional Potential of Medicinal Plants from Asteraceae Family","volume":"17","author":"Sharma","year":"2022","journal-title":"J. Mt. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rolnik, A., and Olas, B. (2021). The plants of the asteraceae family as agents in the protection of human health. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063009"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101642","DOI":"10.1016\/j.isci.2020.101642","article-title":"Furin: A Potential Therapeutic Target for COVID-19","volume":"23","author":"Wu","year":"2020","journal-title":"iScience"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yang, C.W., Hsu, H.Y., Lee, Y.Z., Jan, J.T., Chang, S.Y., and Lin, Y.L. (2023). Natural fucoidans inhibit coronaviruses by targeting viral spike protein and host cell furin. Biochem. Pharmacol., 215.","DOI":"10.1016\/j.bcp.2023.115688"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kocyigit, A., Kan\u0131mdan, E., Yenigun, V.B., Ozman, Z., Bal\u0131bey, F.B., and Durmu\u015f, E. (2024). Olive Leaf Extract Downregulates the Protein Expression of Key SARS-CoV-2 Entry Enzyme ACE-2, TMPRSS2, and Furin. Chem. Biodivers., 21.","DOI":"10.1002\/cbdv.202400717"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ni, J., Wen, X., Wang, S., Zhou, X., and Wang, H.X. (2023). Investigation of the inhibitory combined effect and mechanism of (-)-epigallocatechin gallate and chlorogenic acid on amylase: Evidence of synergistic interaction. Food Biosci., 56.","DOI":"10.1016\/j.fbio.2023.103406"},{"key":"ref_28","first-page":"87","article-title":"The extraction of apigenin and luteolin from the sage Salvia officinalis L. from Jordan","volume":"1","author":"Amr","year":"2000","journal-title":"Work. Living Environ. Prot."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Anagnostou, M., Tomou, E.M., Krigas, N., and Skaltsa, H. (2025). Phenolic constituents of Greek native Salvia species: A comprehensive review. Phytochem. Rev.","DOI":"10.1007\/s11101-024-10062-w"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.indcrop.2012.08.029","article-title":"Evaluation of antioxidant activity, total phenols and phenolic compounds in thyme (Thymus vulgaris L.), sage (Salvia officinalis L.), and marjoram (Origanum majorana L.) extracts","volume":"43","author":"Roby","year":"2013","journal-title":"Ind. Crops Prod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/j.1750-3841.2010.01717.x","article-title":"Synergistic and antagonistic interactions of phenolic compounds found in navel oranges","volume":"75","author":"Freeman","year":"2010","journal-title":"J. Food Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.jfca.2008.03.011","article-title":"Catechin, epicatechin, quercetin, rutin and resveratrol in red grape: Content, in vitro antioxidant activity and interactions","volume":"21","author":"Iacopini","year":"2008","journal-title":"J. Food Compos. Anal."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/17\/3450\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:33:24Z","timestamp":1760034804000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/17\/3450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,22]]},"references-count":32,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["molecules30173450"],"URL":"https:\/\/doi.org\/10.3390\/molecules30173450","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,22]]}}}