Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo
Abstract
:1. Introduction
2. Results
2.1. Spectral Data
Compound L4N (CD3OD)
2.2. In Vitro Study
2.3. In Vivo Study
3. Discussion
4. Materials and Methods
4.1. Isolation of L4N from Phyllanthus Emblica
4.2. Characterization
4.3. Screening for Multidrug-Resistant Bacteria
4.4. In Vitro Studies
4.5. Determination of the Safety Limit of L4N
4.6. In Vivo Study
4.6.1. STEC O111 Oral Infection Model
4.6.2. K. pneumoniae-Sepsis-Induced Infection Model
4.6.3. Biochemical Parameters
4.7. Quantification of Bacterial Shedding
4.8. Statistics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Test Agent | Zone of Inhibition (Mean ± SD) (mm) | |
---|---|---|
STEC O111 | MDR K. pneumonia | |
DMSO | 0.0 ± 0.0 a (R) | 0.0 ± 0.0 a (R) |
AK | 0.0 ± 0.0 a (R) | 0.0 ± 0.0 a (R) |
GEN | 17.0 ± 1.00 b (S) | 8.66 ± 0.57 b (R) |
L4N | 20.6 ± 2.08 c (S) | 18.00 ± 0.0 c (S) |
AK + L4N | 18.0 ± 0.0 b (S) | 18.66 ± 1.15 c (S) |
GEN + L4N | 21.0 ± 1.00 c (S) | 20.00 ± 0.0 d (I) |
Sample | Zone of Inhibition (Mean ± SD) mm | |
---|---|---|
B. cereus | MRSA | |
DMSO | 0.0 ± 0.0 a (R) | 0.0 ± 0.0 a (R) |
PEN | 0.0 ± 0.0 a (R) | 0.0 ± 0.0 a (R) |
VAN | 8.66 ± 0.57 b (R) | 14.66 ± 0.57 b (S) |
L4N | 6.0 ± 1.0 c (R) | 19.0 ± 0 c (S) |
PEN + L4N | 5.66 ± 0.57 c (R) | 14.0 ± 0 b (I) |
VAN + L4N | 19.66 ± 1.52 d (S) | 24.0 ± 1 d (S) |
Sample | MIC (µg/mL) | |
---|---|---|
STEC O111 | MDR K. pneumoniae | |
NC | 0.0 ± 0.0 a | 0.0 ± 0.0 a |
L4N | 26.66 ± 5.23 c | 53.33 ± 8.47 c |
GEN | 2.00 ± 0 b | 8.66 ± 1.15 b |
Sample | MIC (μg/mL) | |
---|---|---|
MRSA | MDR B. cereus | |
NC | 0.0 ± 0.0 a | 0.0 ± 0.0 a |
L4N | 106.66 ± 6.95 c | 213.33 ± 7.9 c |
VAN | 2.00 ± 0 b | 4.0 ± 0 b |
a | b | c | d | |
---|---|---|---|---|
Hemorrhage | 0 | 3 | 0 | 0 |
Thickened interalveolar septa | 0 | 3 | 1 | 1 |
RBCs in alveolar lamina | 0 | 3 | 0 | 0 |
Perivascular oedema | 0 | 4 | 0 | 0 |
a | b | c | d | |
---|---|---|---|---|
Subcapsular hemorrhage | 0 | 2 | 0 | 0 |
Interstitial hemorrhage | 0 | 3 | 0 | 0 |
Necrobiotic changes in tubular epithelium | 0 | 3 | 1 | 1 |
Interstitial inflammatory cell infiltration | 0 | 5 | 1 | 2 |
Renal cast | 0 | 2 | 0 | 0 |
STEC O111 (CFU/g Feces) | K. pneumoniae (CFU/g Feces) | |||||||
Negative Control | Positive Control STEC O111 | STEC O111 then L4N | STEC O111 then GEN | Negative Control | Positive Control K. pneumoniae | K. pneumoniae then L4N | K. pneumoniae then GEN | |
Day zero | 2 × 104 | 3 × 106 | 4 × 104 | 4 × 106 | 36 × 101 | 22 × 102 | 16 × 102 | 36 × 102 |
Day 4 (before challenge and after treatment with streptomycin) | 2 × 101 | 1 × 102 | 0 | 1 × 101 | 10 × 101 | 1 × 102 | 1 × 101 | 1 × 101 |
Day 7 (after challenge) | 2 × 101 | 4 × 109 | 2 × 107 | 1 × 107 | 10 × 106 | 18 × 107 | 19 × 106 | 27 × 106 |
Day 10 (after treatment, 3 successive days of treatment with GEN I.P. once daily) | 2 × 101 | Death | 10 × 103 | 4 × 103 | 7 × 108 | Death | 12 × 104 | >250 × 102 |
Day 17 (after treatment, 7 successive days of treatment with LN I.P. once daily) | 3 × 101 | NA | 3 × 102 | NA | NA | NA | 5 × 102 | NA |
Kidney | 0 | NA | 0 | 1 × 101 | NA | |||
Lung | NA | 0 | >300 × 103 | 5 × 101 | 6 × 102 |
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El-Shiekh, R.A.; Elhemely, M.A.; Naguib, I.A.; Bukhari, S.I.; Elshimy, R. Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo. Molecules 2023, 28, 2609. https://doi.org/10.3390/molecules28062609
El-Shiekh RA, Elhemely MA, Naguib IA, Bukhari SI, Elshimy R. Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo. Molecules. 2023; 28(6):2609. https://doi.org/10.3390/molecules28062609
Chicago/Turabian StyleEl-Shiekh, Riham A., Mai A. Elhemely, Ibrahim A. Naguib, Sarah I. Bukhari, and Rana Elshimy. 2023. "Luteolin 4′-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo" Molecules 28, no. 6: 2609. https://doi.org/10.3390/molecules28062609