Evaluation of the Interaction between Carvacrol and Thymol, Major Compounds of Ptychotis verticillata Essential Oil: Antioxidant, Anti-Inflammatory and Anticancer Activities against Breast Cancer Lines
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Physicochemical, Drug-Likeness, Pharmacokinetics, and In Silico Toxicity
2.3. Antioxidant Activity Protocols
2.3.1. DPPH Scavenging Capacity
2.3.2. ABTS Scavenging Activity
2.3.3. Oxygen Radical Absorbance Capacity
2.4. Anti-Inflammatory Activity
2.4.1. 5-Lipoxygenase (5-LOX) Inhibition
2.4.2. Cyclooxygenase 1/2 (COX-1/2) Inhibition
2.5. Anticancer Activity
2.5.1. Cell Lines and Culture Conditions
2.5.2. Evaluation of Cell Viability
3. Results and Discussion
3.1. Physico-Chemical Properties and Drug-Likeness of Thymol and Carvacrol
3.2. Pharmacokinetics (ADME Properties) of Thymol and Carvacrol and Their Potential Toxicity
3.3. Antioxidant Activity Results
3.4. Anti-Inflammatory Activity Results
3.5. Anticancer Activity against Breast Cancer Lines
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Thymol | Carvacrol |
---|---|---|
Chemical structure | ||
Physico-chemical properties and drug-likeness | ||
MW (g/mol) | 150.221 | 150.221 |
TPSA (Ų) | 20.23 | 20.23 |
Num. H-Bond acceptors | 1 | 1 |
Num. H-Bond donors | 1 | 1 |
Rotatable bonds | 1 | 1 |
LogP | 2.82 | 2.82 |
Lipinski * | Yes, No violation | Yes, No violation |
Egan ** | Yes | Yes |
Veber *** | Yes | Yes |
Bioavailability score | 0.55 | 0.55 |
Bioavailability radars |
In silico Prediction | Thymol | Carvacrol |
---|---|---|
ADME Prediction Absorption-Related Parameters | ||
Water Solubility | −3.01 | −3.31 |
Solubility Class | Soluble | Soluble |
Caco-2 Permeability | −4.44 | −4.41 |
Intestinal Absorption | Absorbed | Absorbed |
Log Kp (cm/s) | −2.64 | −2.64 |
Distribution-related parameters | ||
VDss | 2.91 | 2.72 |
BBB Permeability | −1.82 | −1.99 |
Metabolism-related parameters | ||
CYP2D6, and CYP3A4 Substrate | No | No |
CYP2D6, and CYP3A4 Inhibitors | No | No |
Excretion-related parameters | ||
Total Clearance | 8.67 | 8.65 |
Renal OCT2 Substrate | Non-inhibitor | Non-inhibitor |
Toxicity-related parameters | ||
Predicted LD50 (mg/kg) Predicted Toxicity Class | 640 4 | 810 4 |
Hepatotoxicity Probability | Inactive 0.75 | Inactive 0.75 |
Nephrotoxicity Probability | Inactive 0.72 | Inactive 0.72 |
Carcinogenicity Probability | Inactive 0.60 | Inactive 0.60 |
Immunotoxicity Probability | Inactive 0.93 | Inactive 0.96 |
Mutagenicity Probability | Inactive 0.99 | Inactive 0.99 |
Cytotoxicity Probability | Inactive 0.89 | Inactive 0.89 |
EO/Reference | DPPH Scavenging Capacity IC50 (µg/mL) | ABTS Scavenging Activity IC50 (µg/mL) | Oxygen Radical Absorbance Capacity (mmol TE/g) |
---|---|---|---|
Thymol | 161.02 ± 6.89 | 125.31 ± 6.25 | 2.341 ± 0.009 |
Carvacrol | 249.09 ± 9.04 | 107.88 ± 4.46 | 3.535 ± 0.127 |
Thymol/Carvacrol (1:1) | 43.82 ± 2.41 | 23.29 ± 0.71 | 0.273 ± 0.096 |
Ascorbic acid (AA) | 188.24 ± 6.46 | 25.20 ± 3.06 | - |
Treatments | IC50 Value ± SD (µg/mL) * | Selectivity Index ** | |||||
---|---|---|---|---|---|---|---|
MCF-7 | MDA-MB-231 | MDA-MB-436 | PBMC | MCF-7 | MDA-MB-231 | MDA-MB-436 | |
Thymol | 5.16 ± 0.71 | 8.22 ± 0.94 | 15.77 ± 1.69 | 307.3 ± 3.48 | 59.55 | 37.38 | 19.44 |
Carvacrol | 5.93 ± 0.77 | 9.76 ± 0.23 | 9.50 ± 1.15 | 343.0 ± 2.53 | 57.84 | 35.03 | 36.10 |
Thymol/Carvacrol (1:1) | 0.92 ± 0.09 | 1.46 ± 0.16 | 1.70 ± 0.22 | 246.3 ± 3.78 | 267.71 | 168.96 | 144.88 |
Cisplatin | 8.43 ± 0.92 | 4.60 ± 0.66 | 3.96 ± 0.59 | 25.36 ± 1.40 | 3.01 | 5.51 | 6.40 |
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Taibi, M.; Elbouzidi, A.; Haddou, M.; Baraich, A.; Ou-Yahia, D.; Bellaouchi, R.; Mothana, R.A.; Al-Yousef, H.M.; Asehraou, A.; Addi, M.; et al. Evaluation of the Interaction between Carvacrol and Thymol, Major Compounds of Ptychotis verticillata Essential Oil: Antioxidant, Anti-Inflammatory and Anticancer Activities against Breast Cancer Lines. Life 2024, 14, 1037. https://doi.org/10.3390/life14081037
Taibi M, Elbouzidi A, Haddou M, Baraich A, Ou-Yahia D, Bellaouchi R, Mothana RA, Al-Yousef HM, Asehraou A, Addi M, et al. Evaluation of the Interaction between Carvacrol and Thymol, Major Compounds of Ptychotis verticillata Essential Oil: Antioxidant, Anti-Inflammatory and Anticancer Activities against Breast Cancer Lines. Life. 2024; 14(8):1037. https://doi.org/10.3390/life14081037
Chicago/Turabian StyleTaibi, Mohamed, Amine Elbouzidi, Mounir Haddou, Abdellah Baraich, Douaae Ou-Yahia, Reda Bellaouchi, Ramzi A. Mothana, Hanan M. Al-Yousef, Abdeslam Asehraou, Mohamed Addi, and et al. 2024. "Evaluation of the Interaction between Carvacrol and Thymol, Major Compounds of Ptychotis verticillata Essential Oil: Antioxidant, Anti-Inflammatory and Anticancer Activities against Breast Cancer Lines" Life 14, no. 8: 1037. https://doi.org/10.3390/life14081037