Investigation of the In-Vivo Cytotoxicity and the In Silico-Prediction of MDM2-p53 Inhibitor Potential of Euphorbia peplus Methanolic Extract in Rats
Abstract
:1. Introduction
2. Results
2.1. Experimental Observations
2.2. GC-MS Profile of EPME
2.3. Effects of EPME on Cardiac Injury Markers
2.4. Effects on EPME on Markers of Kidney Injury
2.5. Histopathological and Immunohistochemical Findings
2.6. Molecular Docking Results
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Kits and Chemicals
5.2. Plant Material
5.3. Preparation of Euphorbia Peplus Methanolic Extracts (EPME)
5.4. Gas Chromatography/Mass Spectrometry Analysis (GC–MS) of EPME
5.5. Animal Grouping and Experimental Design
5.6. Sampling
5.7. Serum Biochemical Analysis
5.8. Histopathological and Immunohistochemical Investigation
5.9. Ligand Preparation for Drug-Likeness and Docking
5.10. MDM2 Protein Preparation for Docking
5.11. Docking of Isolated Euphorbia Peplus Compounds into MDM2 Protein
5.12. Statistical Analysis
Author Contributions
Funding
Conflicts of Interest
References
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Compound | MW 1 | Formula | RT (min) | Peak Area% |
---|---|---|---|---|
Di-(2-ethylhexyl) phthalate | 390 | C24H38O4 | 51.23 | 37.07 |
9-Octadecenoic acid “oleic acid” | 282 | C18H34O2 | 45.50 | 28.82 |
Hexadecanoic acid “palmitic acid” | 256 | C16H32O2 | 42.07 | 15.74 |
Lucenin 2 | 610 | C27H30O16 | 48.77 | 4.54 |
à-Gurjunene “humulene” | 204 | C15H24 | 29.89 | 4.36 |
9,12,15-Octadecatrienoic acid, 2,3-dihydroxypropyl ester “glyceryl linolenate” | 352 | C21H36O4 | 43.84 | 3.64 |
Oxiraneundecanoic acid, 3-pentyl-, methyl ester, cis-(CAS) | 312 | C19H36O3 | 45.72 | 2.23 |
9,12-Octadecadienoic acid (Z,Z)-, methyl ester | 294 | C19H34O2 | 43.69 | 2.24 |
Vitamin A aldehyde | 284 | C20H28O | 35.44 | 1.36 |
Parameters | Control | DMSO Treated | EPME Treated | P-Value |
---|---|---|---|---|
Troponin I (ug/L) | 0.01 b ± 0.001 | 0.02 b ± 0.005 | 0.07 a ± 0.016 | <0.001 |
CPK (U/L) | 314.0 b ± 2.5 | 350.0 b ± 53.9 | 652.0 a ± 9.7 | <0.001 |
CK-MB (ng/mL) | 6.0 b ± 0.1 | 8.7 b ± 0.1 | 18.7 a ± 1.7 | <0.001 |
LDH (U/L) | 1698.3 b ± 11.9 | 2224.0 b ± 279.1 | 3853.7a ± 144.7 | <0.001 |
AST (U/L) | 92.5 b ± 1.0 | 89.6 b ± 2.1 | 109.9 a ± 3.9 | 0.001 |
ALP (U/L) | 42.2 b ± 1.2 | 54.9 b ± 1.7 | 81.7 a ± 7.4 | <0.001 |
N | Compound | ΔGb | RMSD | No. of Binding Interactions | H-Bonds | π-Interactions | |||
---|---|---|---|---|---|---|---|---|---|
Name | PubChem CID | Type | Amino Acid | Type | Amino Acid | ||||
1 | Ligand | - | −8.172 | 0.49 | 3 | H-acceptor | HIS 96 | pi-pi | HIS 96 |
H-donor | MET 62 | ||||||||
2 | Palmitic acid | 985 | −7.916 | - | 1 | H-donor | HIS 73 | - | - |
3 | Di-(2-ethylhexyl) phthalate | 8343 | −12.448 | - | 3 | H-donor | MET 62 | H-pi | HIS 96 |
H-pi | HIS 96 | ||||||||
4 | Oleic Acid | 445639 | −12.244 | - | 1 | H-acceptor | HIS 96 | - | - |
5 | Vitamin A aldehyde | 638015 | −9.412 | - | 1 | - | - | H-pi | TYR 67 |
6 | 9,12-Octadecadienoic acid (Z,Z)-, methyl ester (Methyl lineoleate) | 5284421 | −10.9625 | - | 1 | H-acceptor | HIS 96 | - | - |
7 | Glyceryl linolenate | 5367328 | −14.496 | - | 2 | H-donor | ILE 19 | - | - |
H-acceptor | HIS 96 | - | - | ||||||
8 | α-Gurjunene “Humulene” | 15560276 | −6.371 | - | 1 | - | - | H-pi | HIS 96 |
9 | Lucenin 2 | 44257937 | −20.733 | - | 3 | H-donor | VAL 93 | - | - |
H-acceptor | GLN 24 | - | - | ||||||
H-acceptor | HIS 96 | - | - | ||||||
10 | Oxiraneundecanoic acid, 3-pentyl-, methyl ester, cis-(CAS) | 71360559 | −12.626 | - | 1 | H-acceptor | GLN 24 | - | - |
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Abd-Elhakim, Y.M.; Abdo Nassan, M.; Salem, G.A.; Sasi, A.; Aldhahrani, A.; Ben Issa, K.; Abdel-Rahman Mohamed, A. Investigation of the In-Vivo Cytotoxicity and the In Silico-Prediction of MDM2-p53 Inhibitor Potential of Euphorbia peplus Methanolic Extract in Rats. Toxins 2019, 11, 642. https://doi.org/10.3390/toxins11110642
Abd-Elhakim YM, Abdo Nassan M, Salem GA, Sasi A, Aldhahrani A, Ben Issa K, Abdel-Rahman Mohamed A. Investigation of the In-Vivo Cytotoxicity and the In Silico-Prediction of MDM2-p53 Inhibitor Potential of Euphorbia peplus Methanolic Extract in Rats. Toxins. 2019; 11(11):642. https://doi.org/10.3390/toxins11110642
Chicago/Turabian StyleAbd-Elhakim, Yasmina M., Mohamed Abdo Nassan, Gamal A. Salem, Abdelkarim Sasi, Adil Aldhahrani, Khaled Ben Issa, and Amany Abdel-Rahman Mohamed. 2019. "Investigation of the In-Vivo Cytotoxicity and the In Silico-Prediction of MDM2-p53 Inhibitor Potential of Euphorbia peplus Methanolic Extract in Rats" Toxins 11, no. 11: 642. https://doi.org/10.3390/toxins11110642