Pharmacokinetics and Therapeutic Potential of Teucrium polium, a Medicinal and Endangered Species in Ha'il Region, against Liver Damage Associated Hepatotoxicity and Oxidative Injury in Rats: Computational, Biochemical and Histological Studies
Abstract
:1. Introduction
2. Materials and Methods
2.1. Preparation of EA T. polium
2.2. Total Antioxidant Capacities (TAC) Assay
2.3. Scavenging Activity of ABTS Radical Cation
2.4. In Vivo Antioxidant Properties
2.4.1. Animals Experiments
2.4.2. Experimental Protocols
- Group I received drinking water for 15 days and constituted the control group.
- Group II received 0.5 mL/kg of CCl4 in olive oil by gavage for 15 days and constituted the CCl4 group.
- Group III received a seven-day pretreatment with the EA T. polium (25 mg/kg) then received 0.5 mL/kg of CCl4 in olive oil for 15 days. Both EA T. polium and CCl4 were given by oral gavage. This group constituted the CCl4 + EA T. polium group.
- Group IV received the EA of T. polium (25 mg/kg) by gavage for 15 days and constituted the EA of T. polium group.
2.4.3. Samples Collection and Preparation
2.4.4. Serum Parameters
2.4.5. Thiobarbituric Acid Reactive Substances (TBARS) Measurement
2.4.6. Determination of Carbonyl Protein Content
2.4.7. Assessment of Conjugated Dienes (CDs)
2.4.8. Superoxide Dismutase (SOD) Assay
2.4.9. Glutathione Peroxidase (GPx) Assay
2.4.10. Catalase (CAT) Assay
2.4.11. Protein Measurement
2.5. In Silico Molecular Interactions and Pharmacokinetic Assays
2.6. Histopathological Analysis
2.7. Statistical Analysis
3. Results
3.1. TAC of EA T. polium In Vitro
3.2. Serum Biochemical Parameters
3.3. Oxidative/Antioxidative Status
3.4. Druggability and Pharmacokinetic Properties of EA T. polium Main Compounds
3.5. In Silico Molecular Interactions
3.6. Histopathological Study
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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Parameters/Fractions | Hexane | Butanol | Ethyl Acetate |
---|---|---|---|
TAC (EAAs/g extract) | 60.21 ± 33.02 | 92.11 ± 36.33 | 123.85 ± 60 * |
ABTS (mM Equivalents Trolox/mg extract) | 0.11 ± 0.02 | 0.23 ± 0.06 * | 0.62 ± 0.14 ***### |
Enzymes (IU/L) | Control | EA T. polium | CCl4 | CCl4 + EA T. polium |
---|---|---|---|---|
ALT | 1738 ± 44.3 ## | 1768 ± 73.74 # | 1913 ± 37.08 **## | 1805 ± 29.39 |
AST | 137.7 ± 16.47 | 139.8 ± 5.48 | 575.5 ± 58.72 ## | 523.5 ± 52.42 ## |
Treatment/Parameters | Control | EA T. polium | CCl4 | CCl4 + EA T. polium |
---|---|---|---|---|
TBARS (µmol/mg protein) | 5.96 ± 3.09 | 5.90 ± 2.97 | 10.2 ± 3.53 ** | 8.2 ± 2.80 **## |
Carbonyl protein (nmol/mg protein) | 0.69 ± 0.023 | 0.69 ± 0.007 | 1.38 ± 0.013 *** | 1.296 ± 0.004 |
Conjugated dienes (nmol/mg protein) | 9 ± 0.02 | 9.45 ± 0.14 | 13.21 ± 0.04 ** | 11.11 ± 0.37 # |
Parameter/Treatment | Control | EA T. polium | CCl4 | CCl4 + EA T. polium |
---|---|---|---|---|
SOD (Units/mg protein) | 1.62 ± 0.19 | 1.65 ± 0.27 | 0.44 ± 0.09 *** | 0.51 ± 0.01 |
GPx (µmol GSH min−1 mg protein−1) | 0.91 ± 0.014 | 0.92 ± 2.5 | 0.49 ± 0.01 *** | 0.93 ± 0.01 # |
CAT (µmol H2O2/mg protein) | 174.02 ± 44.3 | 176.32 ± 22.18 | 85.9 ± 6.25 *** | 149.4 ± 44.29 ## |
Entry | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Druglikeness/Medicinal Chemistry | ||||||||||||
Consensus Log Po/w | 4.52 | −0.81 | 5.19 | 3.40 | 2.78 | 1.93 | 2.27 | 3.19 | 2.43 | 5.36 | 3.27 | 3.22 |
Lipinski’s Rule | Yes | No | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
Bioavailability Score | 0.85 | 0.17 | 0.55 | 0.55 | 0.55 | 0.55 | 0.55 | 0.55 | 0.55 | 0.55 | 0.55 | 0.55 |
PAINS (alerts) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Synthetic accessibility | 4.01 | 6.33 | 4.74 | 4.08 | 6.17 | 5.96 | 3.20 | 4.58 | 3.74 | 7.01 | 6.36 | 3.42 |
Pharmacokinetics | ||||||||||||
GI absorption | High | Low | High | High | High | High | High | High | High | High | High | High |
BBB permeant | Yes | No | No | No | No | No | No | No | Yes | No | No | Yes |
P-gp substrate | No | Yes | No | No | No | No | No | No | Yes | No | Yes | No |
CYP1A2 inhibitor | Yes | No | No | No | No | No | Yes | No | No | No | No | No |
CYP2C19 inhibitor | No | No | Yes | No | No | No | No | Yes | No | No | No | No |
CYP2C9 inhibitor | Yes | No | Yes | No | No | No | Yes | Yes | No | No | No | No |
CYP2D6 inhibitor | Yes | No | No | No | Yes | No | Yes | No | Yes | No | No | Yes |
CYP3A4 inhibitor | No | No | No | No | Yes | No | Yes | Yes | No | No | No | No |
Log Kp (cm/s) | −4.31 | −9.94 | −5.2 | −8.87 | −7.63 | −8.02 | −0.55 | −6.38 | −6.32 | −5.36 | −7.53 | −5.02 |
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Rahmouni, F.; Badraoui, R.; Ben-Nasr, H.; Bardakci, F.; Elkahoui, S.; Siddiqui, A.J.; Saeed, M.; Snoussi, M.; Saoudi, M.; Rebai, T. Pharmacokinetics and Therapeutic Potential of Teucrium polium, a Medicinal and Endangered Species in Ha'il Region, against Liver Damage Associated Hepatotoxicity and Oxidative Injury in Rats: Computational, Biochemical and Histological Studies. Life 2022, 12, 1092. https://doi.org/10.3390/life12071092
Rahmouni F, Badraoui R, Ben-Nasr H, Bardakci F, Elkahoui S, Siddiqui AJ, Saeed M, Snoussi M, Saoudi M, Rebai T. Pharmacokinetics and Therapeutic Potential of Teucrium polium, a Medicinal and Endangered Species in Ha'il Region, against Liver Damage Associated Hepatotoxicity and Oxidative Injury in Rats: Computational, Biochemical and Histological Studies. Life. 2022; 12(7):1092. https://doi.org/10.3390/life12071092
Chicago/Turabian StyleRahmouni, Fatma, Riadh Badraoui, Hmed Ben-Nasr, Fevzi Bardakci, Salem Elkahoui, Arif J. Siddiqui, Mohd Saeed, Mejdi Snoussi, Mongi Saoudi, and Tarek Rebai. 2022. "Pharmacokinetics and Therapeutic Potential of Teucrium polium, a Medicinal and Endangered Species in Ha'il Region, against Liver Damage Associated Hepatotoxicity and Oxidative Injury in Rats: Computational, Biochemical and Histological Studies" Life 12, no. 7: 1092. https://doi.org/10.3390/life12071092