Modulation of Redox and Inflammatory Signaling in Human Skin Cells Using Phytocannabinoids Applied after UVA Irradiation: In Vitro Studies

Cells. 2024 Jun 3;13(11):965. doi: 10.3390/cells13110965.

Abstract

UVA exposure disturbs the metabolism of skin cells, often inducing oxidative stress and inflammation. Therefore, there is a need for bioactive compounds that limit such consequences without causing undesirable side effects. The aim of this study was to analyse in vitro the effects of the phytocannabinoids cannabigerol (CBG) and cannabidiol (CBD), which differ in terms of biological effects. Furthermore, the combined use of both compounds (CBG+CBD) has been analysed in order to increase their effectiveness in human skin fibroblasts and keratinocytes protection against UVA-induced alternation. The results obtained indicate that the effects of CBG and CBD on the redox balance might indeed be enhanced when both phytocannabinoids are applied concurrently. Those effects include a reduction in NOX activity, ROS levels, and a modification of thioredoxin-dependent antioxidant systems. The reduction in the UVA-induced lipid peroxidation and protein modification has been confirmed through lower levels of 4-HNE-protein adducts and protein carbonyl groups as well as through the recovery of collagen expression. Modification of antioxidant signalling (Nrf2/HO-1) through the administration of CBG+CBD has been proven to be associated with reduced proinflammatory signalling (NFκB/TNFα). Differential metabolic responses of keratinocytes and fibroblasts to the effects of the UVA and phytocannabinoids have indicated possible beneficial protective and regenerative effects of the phytocannabinoids, suggesting their possible application for the purpose of limiting the harmful impact of the UVA on skin cells.

Keywords: UVA radiation; fibroblasts; inflammation; keratinocytes; phytocannabinoids; redox balance.

MeSH terms

  • Antioxidants / pharmacology
  • Cannabidiol* / pharmacology
  • Cannabinoids* / pharmacology
  • Fibroblasts* / drug effects
  • Fibroblasts* / metabolism
  • Fibroblasts* / radiation effects
  • Humans
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Keratinocytes* / drug effects
  • Keratinocytes* / metabolism
  • Keratinocytes* / radiation effects
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / radiation effects
  • NF-E2-Related Factor 2 / metabolism
  • Oxidation-Reduction* / drug effects
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction* / drug effects
  • Skin* / drug effects
  • Skin* / metabolism
  • Skin* / pathology
  • Skin* / radiation effects
  • Ultraviolet Rays* / adverse effects

Substances

  • Cannabinoids
  • Cannabidiol
  • Antioxidants
  • cannabigerol
  • Reactive Oxygen Species
  • NF-E2-Related Factor 2

Grants and funding

The biochemical analysis carried out on cells was supported by the Ministry of Science and Higher Education (Poland) as part of the scientific activity of the Medical University of Bialystok. The funding body did not participate in the design of the study, in the analysis or interpretation of data, or in the writing of the manuscript.