Cannabidiol Protects Human Skin Keratinocytes from Hydrogen-Peroxide-Induced Oxidative Stress via Modulation of the Caspase-1–IL-1β Axis

Abstract

Preclinical and clinical studies support cannabidiol (CBD)'s antioxidant and anti-inflammatory effects, which are linked to its skin protective effects, but there have been limited mechanistic studies reported. Herein we evaluated CBD's protective effects against hydrogen peroxide (H 2 O 2 )-induced oxidative stress in human keratinocyte HaCaT cells and explored its possible mechanism(s) of action. CBD (10 μM) protected HaCaT cells by alleviating H 2 O 2 (200 μM)-induced cytotoxicity (by 11.3%) and reactive oxygen species (total-and mitochondrialderived). Several NLRP3 inflammasome-related genes including CASP1 and IL1B were identified as potential molecular targets for CBD's antioxidant effects by multiplexed gene and network pharmacology analyses. CBD treatment down-regulated the mRNA expression levels of CASP1 and IL1B (by 32.9 and 51.0%, respectively) and reduced IL-1β level (by 16.2%) in H 2 O 2 -stimulated HaCaT cells. Furthermore, CBD inhibited the activity of caspase-1 enzyme (by 15.7%) via direct binding to caspase-1 protein, which was supported by data from a biophysical binding assay (surface plasmon resonance) and a computational docking experiment. In addition, CBD mitigated H 2 O 2 -induced pyroptosis (capase-1-mediated cell death) and apoptosis by 23.6 and 44.0%, respectively. The findings from the current study suggest that CBD exerts protective effects in human keratinocytes via the modulation of the caspase-1-IL-1β axis, supporting its potential skin health applications.

Photoprotective Effects of Cannabidiol against Ultraviolet-B-Induced DNA Damage and Autophagy in Human Keratinocyte Cells and Mouse Skin Tissue

“…Excessive generation of ROS can disrupt cellular redox homeostasis and exacerbate DNA damage, leading to cell apoptosis and inflammation [ 21 , 22 ]. Antioxidant capacity is also an important indicator for evaluating photoprotective capacity.…”

Changes in Phospholipid/Ceramide Profiles and Eicosanoid Levels in the Plasma of Rats Irradiated with UV Rays and Treated Topically with Cannabidiol

“…In recent years, research has been conducted on the effects of cannabidiol (CBD), a phytocannabinoid found in Cannabis sativa L., which does not have psychoactive properties [5] but exhibits antioxidant and anti-inflammatory properties on the skin and skin cells [6,7]. In various experimental models, ranging from a typical in vitro experiment using cell cultures to ex vivo experiments using cells isolated from the skin of patients, and animal studies, the effects of cannabidiol have been extensively evaluated [8][9][10][11][12][13].…”

Protective Effects of Cannabidiol on Chemotherapy-Induced Oral Mucositis via the Nrf2/Keap1/ARE Signaling Pathways

“…ROS reduces the cell viability of keratinocytes and inhibits wound healing in OM [ 37 ]. CBD have an antiapoptotic effect on keratinocytes irradiated by ultraviolet light [ 38 , 39 ]. Considering the antiapoptotic properties of CBD, we evaluated the apoptosis of epithelial cells in mouse tongue tissue by Ki67 staining and TUNEL assay.…”