Wound Healing and Antioxidant Capabilities of Zizyphus mauritiana Fruits: In-Vitro, In-Vivo, and Molecular Modeling Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plants Material
2.2. In-Vitro Antioxidant Activity
2.3. In-Vivo Wound Healing Activity
2.4. LC-MS Analysis
2.5. Molecular Docking
2.6. Prediction of the Antioxidant activity
3. Results and Discussion
3.1. In Vitro Antioxidant Activity
3.1.1. Hydrogen Peroxide Scavenging Activity
3.1.2. Superoxide Radical Scavenging Activity
3.2. Wound Healing Activity
3.2.1. Wound Closure Rate Estimation
3.2.2. Effect of Z. mauritiana Fruit Extract on Expression of TGF-β, TNF-α, IL-1β, Collagen Type I, and VEGF
3.2.3. Histopathological Study
3.3. LC-HRMS Chemical Profiling
3.4. Computational Analysis
3.4.1. Molecular Docking Studies
3.4.2. Antioxidant Activity Prediction
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Sample | IC50 |
---|---|
Zizyphus mauritiana extract | 189.2 ± 1.6 µg/mL |
Ascorbic acid | 194.2 ± 0.8 µg/mL |
Sample | IC50 |
---|---|
Zizyphus mauritiana extract | 146.7 ± 2.1 µg/mL |
Ascorbic acid | 154.4 ± 1.5 µg/mL |
# | Molecule | Energy Score (kcal/mol) | RMSD (Å) |
---|---|---|---|
- | 2AZ5 Co-crystallized ligand | −5.5254 | 1.3787 |
1 | Amphibine H. | −6.6756 | 1.4343 |
2 | Amphibine B. | −6.7857 | 2.0384 |
3 | Amphibine D. | - | - |
4 | Amphibine E. | −5.9343 | 1.5565 |
5 | Amphibine E., N-DeMe or Mauritine J. | −6.8964 | 1.6562 |
6 | Amphibine F | - | - |
7 | Zizogenin or 2,6-Dihydroxyspirostane-3,12-dione | −5.7141 | 1.8788 |
8 | Frangufoline | −6.1900 | 1.8342 |
11 | Mauritine A. | - | - |
12 | Mauritine F. | - | - |
13 | Mauritine E. | −6.6522 | 1.7973 |
14 | Mauritine B. | −6.4077 | 1.4182 |
15 | Mauritine C. | - | - |
16 | Mauritine D. | - | - |
17 | Mauritine H. | −6.3098 | 1.6508 |
19 | Zizimauritic acid C. | −5.5227 | 1.7836 |
20 | Zizimauritic acid C., 21-Me ether | −5.2907 | 1.4763 |
21 | Franganine | −5.7895 | 1.6281 |
22 | Prodelphinidin B. or Gallocatechin(4α→8)gallocatechin | −4.9952 | 1.6455 |
23 | Sativanine A. | −5.9033 | 1.9644 |
25 | Zizyphine F. | −5.5143 | 2.0778 |
# | Molecule | Energy Score (S; kcal/mol) | RMSD (Å) |
---|---|---|---|
- | 6B8Y co-crystallized ligand | −5.102 | 1.1231 |
1 | Amphibine H. | −6.6039 | 1.5284 |
2 | Amphibine B. | - | - |
3 | Amphibine D. | - | - |
4 | Amphibine E. | - | - |
5 | Amphibine E., N-DeMe or Mauritine J. | −4.2228 | 1.5592 |
6 | Amphibine F. | - | - |
7 | Zizogenin or 2,6-Dihydroxyspirostane-3,12-dione | −1.4649 | 1.5668 |
8 | Frangufoline | −4.3323 | 1.5238 |
11 | Mauritine A. | - | - |
12 | Mauritine F. | - | - |
13 | Mauritine E. | −1.8020 | 1.4485 |
14 | Mauritine B. | - | - |
15 | Mauritine C. | - | - |
16 | Mauritine D. | - | - |
17 | Mauritine H. | −8.0128 | 1.3190 |
19 | Zizimauritic acid C. | −3.9723 | 1.6145 |
20 | Zizimauritic acid C., 21-Me ether | - | - |
21 | Franganine | −5.6339 | 1.3131 |
22 | Prodelphinidin B. or Gallocatechin(4α→8)gallocatechin | −5.4270 | 1.2301 |
23 | Sativanine A. | −3.9078 | 1.3504 |
25 | Zizyphine F. | −4.9981 | 1.4643 |
# | Molecule | Energy Score (S; kcal/mol) | RMSD (Å) |
---|---|---|---|
- | 6Y8M co-crystallized ligand | −4.2536 | 1.0950 |
1 | Amphibine H. | −5.2842 | 1.5363 |
2 | Amphibine B. | −4.8328 | 1.8557 |
3 | Amphibine D. | - | - |
4 | Amphibine E. | −4.9107 | 1.8266 |
5 | Amphibine E., N-DeMe or Mauritine J. | −5.4092 | 1.5702 |
6 | Amphibine F. | - | - |
7 | Zizogenin or 2,6-Dihydroxyspirostane-3,12-dione | −4.3238 | 1.7200 |
8 | Frangufoline | −5.3185 | 1.3011 |
11 | Mauritine A. | - | - |
12 | Mauritine F. | - | - |
13 | Mauritine E. | −4.2738 | 1.8927 |
14 | Mauritine B. | −5.6825 | 1.4982 |
15 | Mauritine C. | - | - |
16 | Mauritine D. | - | - |
17 | Mauritine H. | - | - |
19 | Zizimauritic acid C. | −4.3469 | 1.4960 |
20 | Zizimauritic acid C., 21-Me ether | −4.3448 | 1.7335 |
21 | Franganine | −4.6395 | 1.3794 |
22 | Prodelphinidin B. or Gallocatechin(4α→8)gallocatechin | −3.8771 | 1.2185 |
23 | Sativanine A. | - | - |
25 | Zizyphine F. | −4.6249 | 1.9028 |
Active Site | Ligand | Binding Energy Score (S; kcal/mol) | Ligand—Active Site Interactions | ||
---|---|---|---|---|---|
a. a. Residue | Bond Type | Bond Length (Å) | |||
TNFα (PDB ID: 2AZ5) | Co-crystallized ligand | −5.5254 | GLN 61 | H-donor | 2.97 |
TYR 119 | H-pi | 4.08 | |||
Amphibine B. | −6.7857 | TYR 59 | pi-H | 4.02 | |
Sativanine A. | −5.9033 | TYR 119 | H-pi | 3.95 | |
Zizyphine F. | −5.5143 | TYR 59 | pi-pi | 3.85 | |
TGFBR1 kinase (PDB ID: 6B8Y) | Co-crystallized ligand | −5.102 | ASP 351 | H-donor | 2.72 |
HIS 283 | H-acceptor | 2.89 | |||
LYS 232 | pi-H | 3.94 | |||
Amphibine H. | −6.6039 | SER 287 | H-acceptor | 3.07 | |
Mauritine J. | −5.4092 | LYS 337 | H-donor | 3.12 | |
Frangufoline | −4.3323 | ILE 211 | H-donor | 3.22 | |
ASP 290 | H-donor | 3.07 | |||
GLY 286 | H-acceptor | 3.43 | |||
ILE 211 | pi-H | 4.35 | |||
Mauritine E. | −1.8020 | ASP 351 | H-donor | 3.35 | |
ASP 351 | H-donor | 2.88 | |||
LYS 232 | H-acceptor | 3.00 | |||
LYS 337 | pi-H | 3.89 | |||
Zizimauritic acid C. | −3.9723 | ASP 290 | H-donor | 3.39 | |
Franganine | −5.6339 | LYS 232 | H-acceptor | 2.70 | |
Sativanine A. | −3.9078 | GLY 212 | H-acceptor | 3.22 | |
Zizyphine F. | −4.9981 | ASP 290 | H-donor | 3.13 | |
ASP290 | H-donor | 2.92 | |||
Interleukin 1β (PDB ID: 6Y8M) | Co-crystallized ligand | −4.2536 | MET 148 | H-donor | 2.73 |
MET 148 | H-acceptor | 2.94 | |||
THR 147 | H-acceptor | 2.62 | |||
GLN 149 | H-acceptor | 2.46 | |||
Amphibine E. | −4.9107 | GLU 105 | pi-H | 4.25 | |
Mauritine J. | −5.4092 | MET 148 | H-donor | 3.20 | |
ARG 11 | H-acceptor | 2.97 | |||
Zizogenin | −4.3238 | LYS 109 | H-acceptor | 3.09 | |
Mauritine E. | −4.2738 | ARG 11 | pi-cation | 4.34 | |
Mauritine B. | −5.6825 | GLN 149 | H-acceptor | 3.32 | |
LYS 109 | pi-cation | 4.06 | |||
Zizimauritic acid C. | −4.3469 | ASN 108 | H-donor | 2.81 | |
Zizimauritic acid C., 21-Me ether | −4.3448 | GLN 149 | H-acceptor | 3.04 | |
Prodelphinidin B. | −4.8631 | MET 148 | H-donor | 2.76 |
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Shady, N.H.; Soltane, R.; Maher, S.A.; Saber, E.A.; Elrehany, M.A.; Mostafa, Y.A.; Sayed, A.M.; Abdelmohsen, U.R. Wound Healing and Antioxidant Capabilities of Zizyphus mauritiana Fruits: In-Vitro, In-Vivo, and Molecular Modeling Study. Plants 2022, 11, 1392. https://doi.org/10.3390/plants11111392
Shady NH, Soltane R, Maher SA, Saber EA, Elrehany MA, Mostafa YA, Sayed AM, Abdelmohsen UR. Wound Healing and Antioxidant Capabilities of Zizyphus mauritiana Fruits: In-Vitro, In-Vivo, and Molecular Modeling Study. Plants. 2022; 11(11):1392. https://doi.org/10.3390/plants11111392
Chicago/Turabian StyleShady, Nourhan Hisham, Raya Soltane, Sherif A. Maher, Entesar Ali Saber, Mahmoud A. Elrehany, Yaser A. Mostafa, Ahmed M. Sayed, and Usama Ramadan Abdelmohsen. 2022. "Wound Healing and Antioxidant Capabilities of Zizyphus mauritiana Fruits: In-Vitro, In-Vivo, and Molecular Modeling Study" Plants 11, no. 11: 1392. https://doi.org/10.3390/plants11111392