Pharmacological Properties of Chemically Characterized Extracts from Mastic Tree: In Vitro and In Silico Assays
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Collection of Plant Material
2.3. Soxhlet Extraction
2.4. Determination of Extraction Yield
2.5. Fatty Acid GC-MS Analysis of P. lentiscus Extracts
2.6. Identification of Phenolic Compounds by HPLC-DAD
2.7. Antioxidant Activity
2.7.1. Determination of Antioxidants by DPPH Radical Scavenging Activity
2.7.2. β-Carotene Bleaching Assay
2.8. Antimicrobial Activity
2.8.1. Bacterial Strains
2.8.2. Agar-Diffusion Method
2.8.3. Determination of MIC and MBC
2.9. Antifungal Activity
2.9.1. Selection of Fungal Strains for Antifungal Activity Testing Using P. Lentiscus Extract
2.9.2. Agar Diffusion Method
2.9.3. Determination of MIC and MBC
2.10. ADME and Toxicity Prediction
2.11. PASS Prediction
2.12. Molecular Docking Analysis
3. Results
3.1. Extraction Yield
3.2. Fatty Acid Analysis
3.3. HPLC-DAD Analysis
3.4. Antioxidant Activity
3.5. Antibacterial Activity
3.6. Antifungal Activity
3.7. Physiochemical and ADME Prediction Analysis
3.8. Toxicity Prediction Using Pro-Tox II Webserver
3.9. PASS Prediction and Molecular Docking Analysis
3.9.1. PASS Prediction
3.9.2. Molecular Docking Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Molecules | MW * (g/mol) | TPSA (Å2) | H-Bonds | Rotatable Bonds | Lipinski’s Rule of Five (Violations) | Ghose Filter (Violations) | Veber Filter (Violations) | |
---|---|---|---|---|---|---|---|---|
Acceptors | Donors | |||||||
Catechin | 290.27 | 110.38 | 6 | 5 | 1 | Yes | Yes | Yes |
4-Hydroxybenzoic acid | 138.12 | 57.53 | 3 | 1 | 1 | Yes | No (3 violations: MR < 40, MW < 160, number of atoms < 20) | Yes |
p-Coumaric acid | 164.16 | 57.53 | 3 | 1 | 2 | Yes | Yes | Yes |
Naringin | 580.53 | 225.06 | 14 | 8 | 6 | No (3 violations: MW > 500, N or O > 10, NH or OH > 5.) | No (4 violations: MW > 480, WLOGP < −0.4, MR > 130, number of atoms > 70) | No (1 violation: TPSA > 140) |
Quercetin | 302.24 | 131.36 | 7 | 5 | 1 | Yes | Yes | Yes |
o-coumaric acid | 164.16 | 57.53 | 3 | 1 | 2 | Yes | Yes | Yes |
Luteolin | 286.24 | 111.13 | 6 | 3 | 1 | No (3 violations: MW > 500, N or O > 10, NH or OH > 5.) | No (4 violations: MW > 480, WLOGP < −0.4, MR > 130, number of atoms > 70) | No (1 violation: TPSA > 140) |
Proteins/PDB IDs | Native Ligand | Grid Box Size (x, y, z)/Center (x, y, z) | Reference |
---|---|---|---|
DNA Gyrase Topoisomerase II (E. coli)/1KZN | Clorobiocin | (40, 40, 40)/(19.528, 19.500, 43.031) | [38] |
Enoyl-Acyl Carrier Reductase Protein/3GNS | Triclosan | (40, 40, 40)/(−14.280, 0.562, −21.462) | [35,36] |
Cytochrome P450 14 Alpha-Sterol Demethylase/1EA1 | Fluconazole | (40, 40, 40)/(17.702, −3.978, 67.221) | [39,41] |
N-Myristoyl Transferase/1IYL | Fluconazole | (40, 40, 40)/(−11.256, 49.991, 1.040) | [39,41] |
Lipoxygenase/1N8Q | Protocatechuic Acid | (40, 40, 40)/(22.455, 1.293, 20.362) | [42] |
CYP2C9/1OG5 | Warfarin | (12.387, 11.653, 11.654)/(−19.823, 86.686, 38.275) | [42] |
Extracts | Yield (%) | |
---|---|---|
This Work | Literature | |
HEPL 1 | 6.37 ± 0.13 | 2.00 ± 0.10 |
MEPL 2 | 17.5 ± 0.05 | 13.10 ± 0.91 |
Compounds | TR (min) | HEPL (%) |
---|---|---|
D-Limonene | 9.870 | 3.57 ± 0.12 |
Myristic Acid (C14:0) | 20.392 | 6.39 ± 0.15 |
Palmitic Acid (C16:0) | 22.608 | 22.84 ± 0.20 |
Oleic Acid (C18:1) | 24.433 | 23.70 ± 0.13 |
Linoleic Acid (C18:2) | 24.600 | 40.97 ± 0.11 |
10-methyl-Heptadecanoic acid | 24.625 | 1.29 ± 0.01 |
UFA a | 64.670 | |
SFA b | 30.516 | |
UFA/SFA c | 2.120 |
Compounds | TR (min) | MEPL (%) |
---|---|---|
Catechin | 6.077 | 37.045 ± 0.15 |
4-hydroxybenzoic acid | 8.527 | 17.763 ± 0.21 |
p-Coumaric acid | 10.418 | 7.107 ± 0.10 |
Naringin | 11.965 | 8.914 ± 0.09 |
Quercetin | 14.539 | 6.739 ± 0.06 |
Coumaric Acid | 15.473 | 17.589 ± 0.11 |
Luteolin | 16.978 | 4.839 ± 0.02 |
Antioxidant Activity | DPPH | β-Carotene |
---|---|---|
Inhibitory Concentration 50 (μg/mL) | ||
HEPL | 0.58 ± 0.73 | 0.64 ± 0.5 |
MEPL | 0.26 ± 0.13 | 0.19 ± 0.26 |
Ascorbic Acid | 0.15 ± 0.11 | |
BHA | 0.09 ± 0.15 |
Bacterial Strains | Inhibition Zone (mm) | P. lentiscus Extract | |||
---|---|---|---|---|---|
P. lentiscus Extract | Gentamicin (1 mg/mL) | MIC (%) | MBC (%) | MBC/MIC | |
S. aureus | 20.00 | 19.50 | 2 | 4 | 2 |
L. innocua | 15.00 | 21.50 | 4 | 8 | 2 |
E. coli | 07.00 | 20.50 | >16 | >16 | - |
Fungi Strains | Inhibition Zone (mm) | P. lentiscus Extract | |||
---|---|---|---|---|---|
P. lentiscus Extract |
Cycloheximide (1 mg/mL) | MIC (%) | MFC (%) | MFC/MIC | |
G. candidum | 12.00 | 23.00 | 8 | 16 | 2 |
R. glutinis | 22.00 | 21.00 | >16 | >16 | - |
Prediction | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
---|---|---|---|---|---|---|---|
ADME Prediction Absorption Parameters | |||||||
Bioavailability score | 0.55 | 0.85 | 0.55 | 0.17 | 0.55 | 0.85 | 0.55 |
Water Solubility (log mol/L) | −3.117 | −1.877 | −2.378 | −2.919 | −3.221 | −1.56 | −3.294 |
Caco-2 Permeability | −0.283 | 1.151 | 1.21 | −0.658 | −0.057 | 1.158 | 0.286 |
Intestinal Absorption (%) | 68.82 | 83.96 | 93.49 | 25.79 | 75.34 | 91.11 | 82.17 |
Distribution | |||||||
Class of solubility | Soluble | Soluble | Soluble | Soluble | Soluble | Soluble | Soluble |
Log Kp (cm/s) | −7.82 | −6.02 | −6.26 | −10.15 | −7.05 | −5.86 | −6.25 |
VDss (log L/kg) | 1.027 | −1.557 | −1.151 | 0.619 | −0.03 | −0.406 | −0.173 |
BBB Permeability | No | Yes | Yes | No | No | Yes | No |
Metabolism | |||||||
CYP2D6, and CYP3A4 Substrate | No | No | No | No | No | No | No |
CYP2D6, and CYP3A4 Inhibitors | No | No | No | No | No | No | Yes |
Excretion | |||||||
Total Clearance log (mL/min/kg) | 0.183 | 0.593 | 0.662 | 0.318 | 0.484 | 0.746 | 0.568 |
Renal OCT2 Substrate | No | No | No | No | No | No | No |
Predicted LD50 (mg/kg) | Class | Hepatotoxicity | Carcinogenicity | Immunotoxicity | Mutagenicity | Cytotoxicity | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Predi. * | Prob. | Predi. | Prob. | Predi. | Prob. | Predi. | Prob. | Predi. | Prob. | |||
1 | 10,000 | VI | In. | 0.72 | In. | 0.51 | In. | 0.96 | In. | 0.55 | In. | 0.84 |
2 | 2200 | V | In. | 0.52 | In. | 0.51 | In. | 0.99 | In. | 0.99 | In. | 0.86 |
3 | 2850 | V | In. | 0.52 | Ac. | 0.50 | In. | 0.91 | In. | 0.93 | In. | 0.81 |
4 | 2300 | V | In. | 0.81 | In. | 0.80 | Ac. | 0.99 | In. | 0.73 | In. | 0.66 |
5 | 159 | III | In. | 0.69 | Ac. | 0.68 | In. | 0.87 | Ac. | 0.51 | In. | 0.99 |
6 | 2850 | V | In. | 0.52 | Ac. | 0.50 | In. | 0.91 | In. | 0.93 | In. | 0.81 |
7 | 3919 | V | In. | 0.69 | Ac. | 0.68 | In. | 0.97 | Ac. | 0.51 | In. | 0.99 |
Prediction | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
---|---|---|---|---|---|---|---|
PASS Prediction (P act/P ina) | |||||||
Antioxidant | 0.810/0.003 | 0.320/0.020 | 0.553/0.005 | 0.851/0.003 | 0.872/0.003 | 0.553/0.005 | 0.775/0.004 |
Antibacterial | 0.320/0.053 | 0.384/0.034 | 0.343/0.045 | 0.669/0.005 | 0.387/0.033 | 0.343/0.045 | 0.388/0.033 |
Antifungal | 0.552/0.023 | 0.384/0.053 | 0.451/0.039 | 0.816/0.004 | 0.490/0.032 | 0.451/0.039 | 0.520/0.027 |
N° | Compounds | Antibacterial Proteins | Antifungal Proteins | Antioxidant Proteins | |||
---|---|---|---|---|---|---|---|
1KZN | 3GNS | 1EA1 | 1IYL | 1N8Q | 1OG5 | ||
Docking Scores (Kcal/mol) * | |||||||
- | Native Ligand | −9.6 | −6.2 | −5.8 | −5.8 | −6 | −6.6 |
1 | Catechin | −8.3 | −7.1 | −6.6 | −7 | −6.3 | −8.3 |
2 | 4-Hydroxybenzoic acid | −5.6 | −5.5 | −4.5 | −4.7 | −5.4 | −5.3 |
3 | p-coumaric acid | −5.8 | −5.3 | −4.6 | −5.4 | −5.7 | −6.2 |
4 | Naringin | −9.3 | −8.1 | −9.1 | −7.7 | −5.6 | −7.8 |
5 | Quercetin | −8.3 | −7 | −7.1 | −7.1 | −8.3 | −8.8 |
6 | o-coumaric acid | −6.1 | −5.7 | −4.7 | −5.6 | −6.3 | −5.9 |
7 | Luteolin | −8.9 | −7.2 | −7.3 | −7.2 | −6.3 | −8.8 |
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Ouahabi, S.; Loukili, E.H.; Elbouzidi, A.; Taibi, M.; Bouslamti, M.; Nafidi, H.-A.; Salamatullah, A.M.; Saidi, N.; Bellaouchi, R.; Addi, M.; et al. Pharmacological Properties of Chemically Characterized Extracts from Mastic Tree: In Vitro and In Silico Assays. Life 2023, 13, 1393. https://doi.org/10.3390/life13061393
Ouahabi S, Loukili EH, Elbouzidi A, Taibi M, Bouslamti M, Nafidi H-A, Salamatullah AM, Saidi N, Bellaouchi R, Addi M, et al. Pharmacological Properties of Chemically Characterized Extracts from Mastic Tree: In Vitro and In Silico Assays. Life. 2023; 13(6):1393. https://doi.org/10.3390/life13061393
Chicago/Turabian StyleOuahabi, Safae, El Hassania Loukili, Amine Elbouzidi, Mohamed Taibi, Mohammed Bouslamti, Hiba-Allah Nafidi, Ahmad Mohammad Salamatullah, Nezha Saidi, Reda Bellaouchi, Mohamed Addi, and et al. 2023. "Pharmacological Properties of Chemically Characterized Extracts from Mastic Tree: In Vitro and In Silico Assays" Life 13, no. 6: 1393. https://doi.org/10.3390/life13061393