Salvianolic acid B protects against UVB-induced skin aging via activation of NRF2

Phytomedicine. 2024 Jul 25:130:155676. doi: 10.1016/j.phymed.2024.155676. Epub 2024 May 16.

Abstract

Background: Prolonged exposure to sun radiation may result in harmful skin photoaging. Therefore, discovering novel anti-photoaging treatment modalities is critical. An active component isolated from Salvia miltiorrhiza (SM), Salvianolic acid B (Sal-B), is a robust antioxidant and anti-inflammatory agent. This investigation aimed to discover the therapeutic impact and pathways of salvianolic acid B for UVB-induced skin photoaging, an area that remains unexplored.

Methods: We conducted in vitro experiments on human dermal fibroblasts (HDFs) exposed to UVB radiation, assessing cellular senescence, superoxide dismutase (SOD) activity, cell viability, proliferation, migration, levels of reactive oxygen species (ROS), and mitochondrial health. The potential mechanism of Sal-B was analyzed using RNA sequencing, with further validation through Western blotting, PCR, and nuclear factor erythroid 2-related factor 2 (NRF2) silencing methods. In vivo, a model of skin photoaging induced by UVB in nude mice was employed. The collagen fiber levels were assessed utilizing hematoxylin and eosin (H&E), Masson, and Sirus red staining. Additionally, NRF2 and related gene and protein expression levels were identified utilizing PCR and Western blotting.

Results: Sal-B was found to significantly counteract photoaging in UVB-exposed skin fibroblasts, reducing aging-related decline in fibroblast proliferation and an increase in apoptosis. It was observed that Sal-B aids in protecting mitochondria from excessive ROS production by promoting NRF2 nuclear translocation. NRF2 knockdown experiments established its necessity for Sal-B's anti-photoaging effects. The in vivo studies also verified Sal-B's anti-photoaging efficacy, surpassing that of tretinoin (Retino-A). These outcomes offer novel insights into the contribution of Sal-B in developing clinical treatment modalities for UVB-induced photodamage in skin fibroblasts.

Conclusion: In this investigation, we identified the Sal-B protective impact on the senescence of dermal fibroblasts and skin photoaging induced by radiation of UVB. The outcomes suggest Sal-B as a potential modulator of the NRF2 signaling pathway.

Keywords: Mitochondria; NRF2; Salvianolic acid B; Skin aging; Skin fibroblasts; Ultraviolet B.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Benzofurans* / pharmacology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cellular Senescence / drug effects
  • Cellular Senescence / radiation effects
  • Depsides
  • Fibroblasts* / drug effects
  • Fibroblasts* / radiation effects
  • Humans
  • Mice
  • Mice, Nude
  • NF-E2-Related Factor 2* / metabolism
  • Reactive Oxygen Species / metabolism
  • Salvia miltiorrhiza / chemistry
  • Skin / drug effects
  • Skin / radiation effects
  • Skin Aging* / drug effects
  • Skin Aging* / radiation effects
  • Superoxide Dismutase / metabolism
  • Ultraviolet Rays* / adverse effects

Substances

  • Antioxidants
  • Benzofurans
  • Depsides
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Reactive Oxygen Species
  • salvianolic acid B
  • Superoxide Dismutase