Cannabidiol and Cannabigerol Exert Antimicrobial Activity without Compromising Skin Microbiota
Abstract
:1. Introduction
2. Results
2.1. CBD and CBG Purity and Chemical Analysis
2.2. CBG and CBD Hinder Microbial Growth
2.3. CBG and CBD Inhibit Biofilm formation
2.4. CBG and CBD Disrupt Mature Biofilms
2.5. CBD and CBG Impaired S. aureus Adhesion to Keratinocytes
2.6. Evaluation of CBD and CBG as a Preservative in Cosmetic Formulations
2.7. CBG and CBD Have No Significant Impact on Skin Microbiota
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Cannabinoids’ Preparation
Cannabinoids’ Analysis by GC-MS
5.2. Determination of MIC and MLC
5.3. Biofilm Formation Inhibition Assay
5.4. Mature Biofilm Eradication Assay
5.5. Staphylococcus spp. Infection on Keratinocytes
5.5.1. Keratinocytes’ Viability
5.5.2. Staphylococcus spp. Infection of Keratinocytes
5.5.3. Cytokines Quantification
5.6. Challenge Test
5.7. Evaluation of the Impact of Cannabinoids on the Skin Microbiota
5.7.1. 16S rRNA Gene and ITS2 Region Amplification and Sequencing
5.7.2. Sequencing Data Analysis
5.7.3. Determination of Relative Abundance of Staphylococcus Genus, and S. aureus and S. epidermidis Species
5.8. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Vendor | Phase I | (w/v) % |
---|---|---|
AAK (Malmö, Sweden) | Akoline PGPR | 5.00 |
Aprinnova (USA) | Neossance Squalene | 5.00 |
Acofarma (Madrid, Spain) | Caprylic/Capric triglyceride | 7.00 |
Vaseline | 10.00 | |
Lanoline | 10.00 | |
Beeswax | 1.80 | |
Magnesium Stearate | 1.00 | |
Phase II | ||
Deionized water | 55.95 | |
Acofarma (Madrid, Spain) | Glycerin | 3.00 |
Sodium Chloride | 0.75 | |
Phase III | ||
Preservative | 0.50 | |
Total | 100.00 |
Bacteria | Not less than 2.0 log reduction from the initial count at 14 days, and no increase from the 14 days count at 28 days |
Yeast and Moulds | No increase (not more than 0.5 log unit higher than the previous value measured) from the initial calculated count at 14 and 28 days. |
Primer | Forward Primer (5′ ->3′) | Reverse Primer (5′->3′) | Reference |
---|---|---|---|
Universal Bacteria | TCCTACGGGAGGCAGCAGT | CGTATTACCGCGGCTGCTGGCAC | [48] |
Staphylococcus | GGCCGTGTTGAACGTGGTCAAATCA | YATHACCATTTCWGTACCTTCTGGTAA | [49] |
S. aureus | AGGACAATCATGGCAAGCGTAC | AACGGACAACATCTAAACTGGC | [50] |
S. epidermidis | GGCAAATTTGTGGGTCAAGA | TGGCTAATGGTTTGTCACCA | [51] |
Purity (%) | SD | |
---|---|---|
CBD Amyris | 98.63 | 0.37 |
CBD Tocris | 98.44 | 1.02 |
CBD Linnea | 99.36 | 0.40 |
CBG Amyris | 99.35 | 0.02 |
CBG Tocris | 99.48 | 0.19 |
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Compound | S. aureus | S. epidermidis | S. pyogenes | C. acnes | P. innocua | P. aeruginosa | E. coli | C. albicans | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | |
CBG | 25 | 75 | 25 | 50 | 50 | 75 | 500 | 3180 | 10 | 50 | 400 | 5000 | 500 | 5000 | 200 | 400 |
CBG Tocris | 10 | 25 | 25 | 75 | 75 | 100 | 1000 | 3180 | 10 | 25 | 400 | 3180 | 1000 | 3180 | 400 | 500 |
CBD | 10 | 75 | 10 | 25 | 25 | 50 | 500 | 5000 | 25 | 75 | 750 | 5000 | 750 | 5000 | 200 | 400 |
CBD Tocris | 75 | 100 | 50 | 75 | 50 | 100 | >1000 | >5000 | 75 | 100 | 1000 | 3180 | 3180 | 3180 | 250 | 500 |
CBD Linnea | 10 | 25 | 5 | 10 | 10 | 25 | 300 | 5000 | 10 | 50 | 1000 | >5000 | 3180 | >5000 | 200 | 300 |
Vancomycin | 0.34 | 0.7 | 0.17 | 0.34 | 0.17 | 0.34 | 0.7 | 1.4 | 0.09 | 0.17 | - | - | - | - | - | - |
Ciprofloxacin | 3 | 6 | 0.3 | 0.75 | 1.5 | 3 | 0.3 | 0.75 | 0.3 | 0.3 | 3 | 6 | 6 | 15 | - | - |
Colistin | - | - | - | - | - | - | - | - | - | - | 0.4 | 4.3 | 0.4 | 0.9 | - | - |
Log Variation | Day 14 | Day 28 | ||||||
---|---|---|---|---|---|---|---|---|
CBG | CBD | No Preservative | Phenoxyethanol | CBG | CBD | No Preservative | Phenoxyethanol | |
Staphylococcus aureus | 2.1 | 2.0 | 0.7 | 6.0 | No increase | |||
Escherichia coli | 2.0 | 2.0 | 0.4 | 2.1 | ||||
Pseudomonas aeruginosa | 2.0 | 0.8 | −0.5 | 1.5 | ||||
Candida albicans | No increase | |||||||
Aspergillus brasiliensis | No increase | Increase | No increase | No increase | Increase | No increase |
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Luz-Veiga, M.; Amorim, M.; Pinto-Ribeiro, I.; Oliveira, A.L.S.; Silva, S.; Pimentel, L.L.; Rodríguez-Alcalá, L.M.; Madureira, R.; Pintado, M.; Azevedo-Silva, J.; et al. Cannabidiol and Cannabigerol Exert Antimicrobial Activity without Compromising Skin Microbiota. Int. J. Mol. Sci. 2023, 24, 2389. https://doi.org/10.3390/ijms24032389
Luz-Veiga M, Amorim M, Pinto-Ribeiro I, Oliveira ALS, Silva S, Pimentel LL, Rodríguez-Alcalá LM, Madureira R, Pintado M, Azevedo-Silva J, et al. Cannabidiol and Cannabigerol Exert Antimicrobial Activity without Compromising Skin Microbiota. International Journal of Molecular Sciences. 2023; 24(3):2389. https://doi.org/10.3390/ijms24032389
Chicago/Turabian StyleLuz-Veiga, Mariana, Manuela Amorim, Inês Pinto-Ribeiro, Ana L. S. Oliveira, Sara Silva, Lígia L. Pimentel, Luís M. Rodríguez-Alcalá, Raquel Madureira, Manuela Pintado, João Azevedo-Silva, and et al. 2023. "Cannabidiol and Cannabigerol Exert Antimicrobial Activity without Compromising Skin Microbiota" International Journal of Molecular Sciences 24, no. 3: 2389. https://doi.org/10.3390/ijms24032389
APA StyleLuz-Veiga, M., Amorim, M., Pinto-Ribeiro, I., Oliveira, A. L. S., Silva, S., Pimentel, L. L., Rodríguez-Alcalá, L. M., Madureira, R., Pintado, M., Azevedo-Silva, J., & Fernandes, J. (2023). Cannabidiol and Cannabigerol Exert Antimicrobial Activity without Compromising Skin Microbiota. International Journal of Molecular Sciences, 24(3), 2389. https://doi.org/10.3390/ijms24032389