Oral administration of punicalagin attenuates imiquimod-induced psoriasis by reducing ROS generation and inflammation via MAPK/ERK and NF-κB signaling pathways

Phytother Res. 2024 Feb;38(2):713-726. doi: 10.1002/ptr.8071. Epub 2023 Nov 27.

Abstract

Psoriasis, an immune-mediated chronic inflammatory skin disease, imposes a huge mental and physical burden on patients and severely affects their quality of life. Punicalagin (PU), the most abundant ellagitannin in pomegranates, has become a research hotspot owing to its diverse biological activities. However, its effects on psoriasis remain unclear. We explored the impact and molecular mechanism of PU on M5-stimulated keratinocyte cell lines and imiquimod (IMQ)-induced psoriasis-like skin inflammation in BABL/c mice using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), hematoxylin and eosin (H&E) stain, immunohistochemistry, and immunofluorescent. Administration of PU-enriched pomegranate extract at dosages of 150 and 250 mg/kg/day markedly attenuated psoriatic severity, abrogated splenomegaly, and reduced IMQ-induced abnormal epidermal proliferation, CD4+ T-cell infiltration, and inflammatory factor expression. Moreover, PU could decrease expression levels of pro-inflammatory cytokines, such as IL-1β, IL-1α, IL-6, IL-8, TNF-α, IL-17A, IL-22, IL-23A, and reactive oxygen species (ROS), followed by keratinocyte proliferation inhibition in the M5-stimulated cell line model of inflammation through inhibition of mitogen-activated protein kinases/extracellular regulated protein kinases (MAPK/ERK) and nuclear factor kappaB (NF-κB) signaling pathways. Our results indicate that PU may serve as a promising nutritional intervention for psoriasis by ameliorating cellular oxidative stress and inflammation.

Keywords: inflammation; keratinocyte; psoriasis; punicalagin; reactive oxygen species.

MeSH terms

  • Administration, Oral
  • Animals
  • Disease Models, Animal
  • Humans
  • Hydrolyzable Tannins / pharmacology
  • Hydrolyzable Tannins / therapeutic use
  • Imiquimod / adverse effects
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Keratinocytes
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • NF-kappa B / metabolism
  • Psoriasis* / chemically induced
  • Psoriasis* / drug therapy
  • Quality of Life
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Skin
  • Skin Diseases*

Substances

  • NF-kappa B
  • Imiquimod
  • punicalagin
  • Hydrolyzable Tannins
  • Reactive Oxygen Species
  • Mitogen-Activated Protein Kinase Kinases