Bakuchiol and Ethyl (Linoleate/Oleate) Synergistically Modulate Endocannabinoid Tone in Keratinocytes and Repress Inflammatory Pathway mRNAs

BAK + ELN hypothesized mechanisms of action. BAK + ELN inhibits FABP5 and FAAH, resulting in an increased abundance of eCB ligands (AEA, 2-AG, OEA, PEA). Ligands interact with receptors (CB1, CB2, TRPV1) with downstream anti-inflammatory effects. Such effects are mediated by decreased TLR3 expression with inhibition of transcription factors (e.g., NF-κB, IRF3, ISGF3). Loss of NF-κB activity blocks the activation of COX-2 by TNF, whereas loss of IRF3 and ISGF3 DNA binding decreases type I IFN gene expression, leading to decreased inflammatory cell activation. Loss of FABP5 and FAAH activity favors a proliferative KC phenotype, mediated by decreased abundance of linoleic acid 13(S)-HODE. The risk of skin barrier compromise is countered by conversion of ELN to linoleic acid and loss of cortisol production. The figure was created using BioRender. 13(S)-HODE, 13(S)-hydroxyoctadecadienoic acid; 2-AG, 2-arachidonoyl glycerol; AEA, anandamide; BAK, bakuchiol; CB1, cannabidiol type 1; CB2, cannabidiol type 2; eCB, endocannabinoid; ELN, ethyl (linoleate/oleate); FAAH, fatty acid amide hydrolase; IRF3, IFN regulatory factor 3; OEA, oleoylethanolamide; PEA, palmitoylethanolamide; TLR3, toll-like receptor 3.

Publication

Bakuchiol and Ethyl (Linoleate/Oleate) Synergistically Modulate Endocannabinoid Tone in Keratinocytes and Repress Inflammatory Pathway mRNAs. (2023) William R. Swindell, et al. JID Innov. 2023 May;3(3):100178. Figure: F17. Homo sapiens

Disease mentions