Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo
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′-neohesperidoside (L4N) has antibacterial and synergistic activitie...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/6/2609 |
| _version_ | 1797609903410380800 |
|---|---|
| author | Riham A. El-Shiekh Mai A. Elhemely Ibrahim A. Naguib Sarah I. Bukhari Rana Elshimy |
| author_facet | Riham A. El-Shiekh Mai A. Elhemely Ibrahim A. Naguib Sarah I. Bukhari Rana Elshimy |
| author_sort | Riham A. El-Shiekh |
| collection | DOAJ |
| description | 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′-neohesperidoside (L4N) has antibacterial and synergistic activities against four antibiotic-resistant pathogens: methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), <i>Klebsiella pneumoniae</i>, <i>fos</i>A-positive shiga toxin producing the <i>Escherichia coli</i> serogroup O111 (STEC O111), and <i>Bacillus cereus</i>. In vitro antimicrobial susceptibility testing revealed highly potent anti-MRSA (MIC of 106.66 ± 6.95 µg/mL), anti-<i>K. pneumoniae</i> (MIC of 53.33 ± 8.47 µg/mL) and anti-STEC O111 (MIC of 26.66 ± 5.23 µg/mL) activities. Significant synergistic combination was clearly noted in the case of gentamycin (GEN) against Gram-negative bacteria. In the case of <i>B. cereus</i>, the combination of vancomycin (VAN) with L4N could efficiently inhibit bacterial growth, despite the pathogen being VAN-resistant (MIC of 213.33 ± 7.9 µg/mL). In vivo evaluation of L4N showed significant decreases in <i>K. pneumoniae</i> and STEC shedding and colonization. Treatment could significantly diminish the levels of pro-inflammatory markers, tumor necrosis factor-alpha (TNF-α), 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-<i>K. pneumoniae</i> potential, a finding which is reported here for the first time. |
| first_indexed | 2024-03-11T06:07:07Z |
| format | Article |
| id | doaj.art-31f8c0508eaa4711b49fdc0da7067cbb |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T06:07:07Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-31f8c0508eaa4711b49fdc0da7067cbb2023-11-17T12:52:43ZengMDPI AGMolecules1420-30492023-03-01286260910.3390/molecules28062609Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In VivoRiham A. El-Shiekh0Mai A. Elhemely1Ibrahim A. Naguib2Sarah I. Bukhari3Rana Elshimy4Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo 11562, EgyptSchool of Medical Sciences, Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M20 4GJ, UKDepartment of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Microbiology and Immunology, Faculty of Pharmacy, Ahram Canadian University, Giza 12451, EgyptMultidrug 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′-neohesperidoside (L4N) has antibacterial and synergistic activities against four antibiotic-resistant pathogens: methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), <i>Klebsiella pneumoniae</i>, <i>fos</i>A-positive shiga toxin producing the <i>Escherichia coli</i> serogroup O111 (STEC O111), and <i>Bacillus cereus</i>. In vitro antimicrobial susceptibility testing revealed highly potent anti-MRSA (MIC of 106.66 ± 6.95 µg/mL), anti-<i>K. pneumoniae</i> (MIC of 53.33 ± 8.47 µg/mL) and anti-STEC O111 (MIC of 26.66 ± 5.23 µg/mL) activities. Significant synergistic combination was clearly noted in the case of gentamycin (GEN) against Gram-negative bacteria. In the case of <i>B. cereus</i>, the combination of vancomycin (VAN) with L4N could efficiently inhibit bacterial growth, despite the pathogen being VAN-resistant (MIC of 213.33 ± 7.9 µg/mL). In vivo evaluation of L4N showed significant decreases in <i>K. pneumoniae</i> and STEC shedding and colonization. Treatment could significantly diminish the levels of pro-inflammatory markers, tumor necrosis factor-alpha (TNF-α), 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-<i>K. pneumoniae</i> potential, a finding which is reported here for the first time.https://www.mdpi.com/1420-3049/28/6/2609STEC O111<i>K. pneumoniae</i>antimicrobial resistanceluteolin 4′-neohesperidosideflavonoidsantibacterial |
| spellingShingle | Riham A. El-Shiekh Mai A. Elhemely Ibrahim A. Naguib Sarah I. Bukhari Rana Elshimy Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo Molecules STEC O111 <i>K. pneumoniae</i> antimicrobial resistance luteolin 4′-neohesperidoside flavonoids antibacterial |
| title | Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo |
| title_full | Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo |
| title_fullStr | Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo |
| title_full_unstemmed | Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo |
| title_short | Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo |
| title_sort | luteolin 4 neohesperidoside inhibits clinically isolated resistant bacteria in vitro and in vivo |
| topic | STEC O111 <i>K. pneumoniae</i> antimicrobial resistance luteolin 4′-neohesperidoside flavonoids antibacterial |
| url | https://www.mdpi.com/1420-3049/28/6/2609 |
| work_keys_str_mv | AT rihamaelshiekh luteolin4neohesperidosideinhibitsclinicallyisolatedresistantbacteriainvitroandinvivo AT maiaelhemely luteolin4neohesperidosideinhibitsclinicallyisolatedresistantbacteriainvitroandinvivo AT ibrahimanaguib luteolin4neohesperidosideinhibitsclinicallyisolatedresistantbacteriainvitroandinvivo AT sarahibukhari luteolin4neohesperidosideinhibitsclinicallyisolatedresistantbacteriainvitroandinvivo AT ranaelshimy luteolin4neohesperidosideinhibitsclinicallyisolatedresistantbacteriainvitroandinvivo |