{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T17:36:08Z","timestamp":1773941768000,"version":"3.50.1"},"reference-count":67,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Propolis, a natural bee-derived product rich in diverse phytochemicals with potential therapeutic benefits, remains underexplored in Algeria. This study investigated the molecular profile, antioxidant capacity, and antibacterial activity of propolis sourced from two bioclimatically distinct Algerian regions (humid subtropical Batna and hot desert Biskra) using electrospray ionization mass spectrometry, ultra-high-performance liquid chromatography with diode array detection, and gas chromatography\u2013mass spectrometry. Significant regional variations were observed, with propolis extract 2 (PE2) exhibiting a higher bioactive content, including a constituent not previously reported in propolis. Antioxidant assays (2,2-diphenyl-1-picrylhydrazyl, 2,2\u2032-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), ferric reducing antioxidant power, and phenanthroline) demonstrated that PE2 consistently outperformed propolis extract 1 and the reference standards (DPPH IC50: 27.74 \u00b5g\/mL; FRAP: 5.16 \u00b5g\/mL). Antibacterial testing demonstrated potent bactericidal effects, particularly for PE2, with minimum inhibitory concentration values equivalent to the minimum bactericidal concentrations required against Staphylococcus aureus ATCC 25923 (18.75 \u00b5g\/mL) and Escherichia coli ATCC 25922 (133 \u00b5g\/mL). Molecular docking identified nine bioactive compounds with high KEAP1 binding affinity, with 1,3-O-caffeoyl-dihydrocaffeoylglycerol (first time reported in propolis) showing the strongest binding affinity (\u221211.02 Kcal\/mol). In silico pharmacokinetic predictions further verified its drug-like properties. These findings suggest the tested Algerian propolis samples, as a source of natural alternative antioxidants and antimicrobials, provide a basis for future research in drug discovery and development.<\/jats:p>","DOI":"10.3390\/cimb47090761","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T07:33:02Z","timestamp":1758007982000},"page":"761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparative Molecular Profiling and Bioactivity Analysis of Algerian Propolis: Antioxidant, Antibacterial Activities, and In Silico NRF2-KEAP1 Pathway Modulation"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5593-2126","authenticated-orcid":false,"given":"Amel","family":"Reguig","sequence":"first","affiliation":[{"name":"DEDSPAZA Laboratory, Department of Agronomical Sciences, Faculty of Exact Sciences and Natural and Life Sciences, University of Biskra, Biskra 07000, Algeria"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1509-5319","authenticated-orcid":false,"given":"Ahmed","family":"Messai","sequence":"additional","affiliation":[{"name":"PIARA Laboratory, Department of Agronomical Sciences, Faculty of Exact Sciences and Natural and Life Sciences, University of Biskra, Biskra 07000, Algeria"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1694-3551","authenticated-orcid":false,"given":"Ibtissam Kahina","family":"Bedaida","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology of Bioactive Molecules and Cellular Physiopathology (LBMBPC), Faculty of Natural and Life Sciences, University of Batna 2, Batna 05000, Algeria"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4249-7089","authenticated-orcid":false,"given":"Diana C. G. A.","family":"Pinto","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4612-4642","authenticated-orcid":false,"given":"Chawki","family":"Bensouici","sequence":"additional","affiliation":[{"name":"National Center for Biotechnological Research (CRBT), BP E73 Ali Mendjili, Constantine 25000, Algeria"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7723-6834","authenticated-orcid":false,"given":"Abdelmoneim Tarek","family":"Ouamane","sequence":"additional","affiliation":[{"name":"Center for Scientific and Technical Research on Arid Regions (CRSTRA), Biskra 07000, Algeria"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-8286","authenticated-orcid":false,"given":"Artur M. S.","family":"Silva","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0444-2303","authenticated-orcid":false,"given":"Jean-Philippe","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Universit\u00e9 de Montr\u00e9al, Saint-Hyacinthe, QC J2S 2M2, Canada"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Etxegarai-Legarreta, O., and Sanchez-Famoso, V. (2022). The role of beekeeping in the generation of goods and services: The interrelation between environmental, socioeconomic, and sociocultural utilities. 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