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| Status |
Public on Nov 23, 2022 |
| Title |
Bakuchiol and ethyl (linoleate/oleate) synergistically modulate endocannabinoid tone in keratinocytes and repress inflammatory pathway mRNAs |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The endocannabinoid (eCB) system plays an active role in epidermal homeostasis. Phytocannabinoids such as CBD modulate this system but also act through eCB-independent mechanisms. This study evaluated effects of CBD, bakuchiol (BAK) and ethyl (linoleate/oleate) (ELN) in keratinocytes (KCs) and reconstituted human epidermis (RHE). Molecular docking simulations showed that each compound binds the active site of the eCB carrier fatty-acid-binding protein 5 (FABP5). However, BAK and ethyl linoleate bound this site with highest affinity when combined 1:1 (w/w) and in vitro assays showed that BAK+ELN most effectively inhibited FABP5 and fatty acid amide hydrolase (FAAH). In TNF-stimulated KCs, BAK+ELN reversed TNF-induced expression shifts and uniquely down-regulated type I interferon genes and PTGS2 (COX-2). BAK+ELN also repressed expression of genes linked to KC differentiation but up-regulated those associated with proliferation. Finally, BAK+ELN inhibited cortisol secretion in RHE skin (not observed with CBD). These results support a model in which BAK and ELN synergistically interact to inhibit eCB degradation, favoring eCB mobilization and inhibition of downstream inflammatory mediators (e.g., TNF, COX-2, type I interferon). Topical combination of these ingredients may thus enhance cutaneous eCB tone or potentiate other modulators, suggesting new ways to modulate the eCB system for innovative skincare product development.
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| Overall design |
We generated 12 samples with treatments corresponding to non-treated control KCs (CTL, n = 2), TNF-treated KCs (TNF, n = 2), KCs treated with TNF and CBD (TNF+CBD, n = 2), KCs treated with TNF and bakuchiol (TNF+BAK, n = 2), KCs treated with TNF and ethyl (linoleate/oleate) (TNF+ELN, n = 2), and KCs treated with TNF and 1:1 (w/w) combination of bakuchiol and ethyl (linoleate/oleate) (BAK+ELN, n = 2).
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| Contributor(s) |
Swindell WR, Bojanowski K, Chaudhuri RK |
| Citation(s) |
36992949 |
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| Submission date |
Oct 26, 2022 |
| Last update date |
Apr 04, 2023 |
| Contact name |
William R Swindell |
| E-mail(s) |
William.Swindell@UTSouthwestern.edu
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| Organization name |
UT Southwestern Medical Center
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| Department |
Internal Medicine
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| Street address |
6201 Harry Hines Blvd
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-9175 |
| Country |
USA |
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| Platforms (1) |
| GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA894510 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE216614_RAW.tar |
13.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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