{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T19:08:06Z","timestamp":1784574486475,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"crossref","award":["RSP2023R497"],"award-info":[{"award-number":["RSP2023R497"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Molecules"],"abstract":"<jats:p>Multidrug resistance (MDR) pathogens are usually associated with higher morbidity and mortality rates. Flavonoids are good candidates for the development of new potential antimicrobials. This research investigated whether luteolin 4\u2032-neohesperidoside (L4N) has antibacterial and synergistic activities against four antibiotic-resistant pathogens: methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, fosA-positive shiga toxin producing the Escherichia coli serogroup O111 (STEC O111), and Bacillus cereus. In vitro antimicrobial susceptibility testing revealed highly potent anti-MRSA (MIC of 106.66 \u00b1 6.95 \u00b5g\/mL), anti-K. pneumoniae (MIC of 53.33 \u00b1 8.47 \u00b5g\/mL) and anti-STEC O111 (MIC of 26.66 \u00b1 5.23 \u00b5g\/mL) activities. Significant synergistic combination was clearly noted in the case of gentamycin (GEN) against Gram-negative bacteria. In the case of B. cereus, the combination of vancomycin (VAN) with L4N could efficiently inhibit bacterial growth, despite the pathogen being VAN-resistant (MIC of 213.33 \u00b1 7.9 \u00b5g\/mL). In vivo evaluation of L4N showed significant decreases in K. pneumoniae and STEC shedding and colonization. Treatment could significantly diminish the levels of pro-inflammatory markers, tumor necrosis factor-alpha (TNF-\u03b1), and immunoglobulin (IgM). Additionally, the renal and pulmonary lesions were remarkably enhanced, with a significant decrease in the bacterial loads in the tissues. Finally, this study presents L4N as a potent substitute for traditional antibiotics with anti-STEC O111 and anti-K. pneumoniae potential, a finding which is reported here for the first time.<\/jats:p>","DOI":"10.3390\/molecules28062609","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T02:33:36Z","timestamp":1678761216000},"page":"2609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Luteolin 4\u2032-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3179-3352","authenticated-orcid":false,"given":"Riham A.","family":"El-Shiekh","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai A.","family":"Elhemely","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M20 4GJ, UK"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5923-1466","authenticated-orcid":false,"given":"Ibrahim A.","family":"Naguib","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6002-9249","authenticated-orcid":false,"given":"Sarah I.","family":"Bukhari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5381-0037","authenticated-orcid":false,"given":"Rana","family":"Elshimy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Ahram Canadian University, Giza 12451, Egypt"},{"name":"Department of Microbiology and Immunology, Egyptian Drug Authority, Giza 12511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alhadrami, H.A., Hamed, A.A., Hassan, H.M., Belbahri, L., Rateb, M.E., and Sayed, A.M. 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