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

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.