Abstract
Cannabidiol (CBD) is abundant in the Cannabis sativa plant and exhibits complex immunomodulatory, anxiolytic, antioxidant, and antiepileptic properties. Several studies suggest that CBD could be used for different purposes in alcohol use disorder (AUD) and alcohol-related injuries to the brain and the liver. In this study, we focused on analyzing transcriptional alterations in human dermal fibroblasts (HDFs) cell line challenged simultaneously with ethanol and CBD as an ethanol-protective agent. We aimed to expose the genes and pathways responsible for at least some of the CBD effects in those cells that can be related to the AUD. Transcriptome analysis was performed using HDFs cell line that expresses both cannabinoid receptors and can metabolize ethanol through alcohol dehydrogenase activity. Fibroblasts are also responsible for the progression of liver fibrosis, a common comorbidity in AUD. With the use of a cellular test, we found that CBD at the lowest applied concentration (0.75 μM) was able to stimulate depressed metabolism and reduce the level of apoptosis of cells treated with different concentrations of ethanol to the level observed in the control cells. Similar observations were made at the transcriptome level, in which cells treated with ethanol and CBD had similar expression profiles to the control cells. CBD also affects several genes connected with extracellular matrix formation (especially its collagen constituent), which can have potential implications for, e.g., fibrosis process.
Keywords: Alcohol use disorder; CBD; Cannabidiol; Ethanol; Fibroblasts; Fibrosis.
© 2024. The Author(s).
References
-
- Adamek A, Kasprzak A (2018) Insulin-like growth factor (IGF) system in liver diseases. Int J Mol Sci 19(5):1308. https://doi.org/10.3390/ijms19051308 – DOI – PubMed – PMC
- Alves P, Amaral C, Teixeira N, Correia-da-Silva G (2021) Cannabidiol disrupts apoptosis, autophagy and invasion processes of placental trophoblasts. Arch Toxicol 95:3393–3406. https://doi.org/10.1007/s00204-021-03122-z – DOI – PubMed
- Anand U, Jones B, Korchev Y, Bloom SR, Pacchetti B, Anand P, Sodergren MH (2020) CBD effects on TRPV1 signaling pathways in cultured DRG neurons. J Pain Res 13:2269–2278. https://doi.org/10.2147/JPR.S258433 – DOI – PubMed – PMC
- Anders S, Pyl PT, Huber W (2015) HTSeq–a Python framework to work with high-throughput sequencing data. Bioinformatics 31:166–169. https://doi.org/10.1093/bioinformatics/btu638 – DOI – PubMed
- Atalay S, Jarocka-Karpowicz I, Skrzydlewska E (2019) Antioxidative and anti-inflammatory properties of cannabidiol. Antioxidants 9(1):21. https://doi.org/10.3390/antiox9010021 – DOI – PubMed – PMC