Nrf2- and Bach1 May Play a Role in the Modulation of Ultraviolet A-Induced Oxidative Stress by Acetyl-11-Keto-β-Boswellic Acid in Skin Keratinocytes

Skin Pharmacol Physiol. 2017;30(1):13-23. doi: 10.1159/000452744. Epub 2017 Feb 1.

Abstract

Background: Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress with damage to various cellular components and concomitant inflammation and carcinogenesis.

Objective: The aim of this study is to investigate the protective effect of acetyl-11-keto-β-boswellic acid (AKBA) against UVA radiation on human skin keratinocytes.

Methods: HaCaT cells were pretreated with AKBA followed by UVA irradiation. Radiation effects on cell morphology, cell viability, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymes were examined.

Results: AKBA reduces UVA irradiation-induced cell viability loss, accompanied by a decreased production of UVA-induced ROS, decreased malondialdehyde, and increased superoxide dismutase expression. In addition, AKBA increased basal and UVA-induced levels of Nrf2 (NF-E2-related factor 2), the redox-sensitive factor, and its target genes NQO1 and heme oxygenase-1 (HO-1), whereas expression of the transcriptional repressor Bach1 (BTB and CNC homology 1) was reduced. Furthermore, the cytoprotective effects of AKBA against UVA-derived oxidative damage were accompanied by modulating expression of inflammatory mediators (i.e., cyclooxygenase-2 and nuclear factor-κB) and NOX1.

Conclusions: AKBA protects skin cells from UVA-induced damage by modulating inflammatory mediators and/or ROS production. Therefore, AKBA has potential in the development of skin care products.

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / genetics
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cyclooxygenase 2 / metabolism
  • Cytoprotection / genetics
  • Cytoprotection / physiology
  • Fanconi Anemia Complementation Group Proteins / genetics
  • Heme Oxygenase-1 / genetics
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NADPH Oxidase 1
  • NADPH Oxidases / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / radiation effects
  • Reactive Oxygen Species / metabolism
  • Skin / cytology
  • Triterpenes / pharmacology*
  • Ultraviolet Rays*

Substances

  • BACH1 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • Fanconi Anemia Complementation Group Proteins
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human
  • Reactive Oxygen Species
  • Triterpenes
  • acetyl-11-ketoboswellic acid
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • NADPH Oxidase 1
  • NADPH Oxidases
  • NOX1 protein, human
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human