Abstract
Psoriasis is a chronic and inflammatory skin disorder characterized by inflammation and epidermal hyperplasia. Punicalagin (PUN) is a main active ingredient of pomegranate (Punica granatum L.) peel with multiple biological activities, such as antibacterial, antioxidant and anti-tumor effects. However, the potential effect of PUN on psoriasis remains unknown. In this study, we want to investigate the pharmacological effect of PUN on psoriasis by using imiquimod (IMQ)-induced psoriatic mice model in vivo and tumor necrosis factor a (TNF-α) and interleukin-17A (IL-17A)-stimulated HaCaT cells in vitro. Our results showed that PUN can effectively alleviate the severity of psoriasis-like symptoms. Mechanistically, PUN potently suppresses the aberrant upregulation of interleukin-1β (IL-1β) and subsequent IL-1β-mediated inflammatory cascade in keratinocytes by inhibiting the nuclear factor kappa B (NF-κB) activation and cleaved caspase-1 expression in vitro and in vivo. Taken together, our findings indicate that PUN can relieve psoriasis by repressing NF-κB-mediated IL-1β transcription and caspase-1-regulated IL-1β secretion, which provide evidence that PUN might represent a novel and promising candidate for the treatment of psoriasis.
Highlights
IntroductionRecurrent, inflammatory skin disease affecting more than 60 million people worldwide (Parisi et al, 2013)
Psoriasis is a chronic, recurrent, inflammatory skin disease affecting more than 60 million people worldwide (Parisi et al, 2013)
We found that PUN can relieve psoriasis-like symptoms by suppressing the nuclear factor kappa B (NF-κB)-mediated IL-1β transcription and caspase-1-regulated IL-1β secretion in vivo and in vitro
Summary
Recurrent, inflammatory skin disease affecting more than 60 million people worldwide (Parisi et al, 2013). Despite the newly developed biologics, such as adalimumab, guselkumab and mirikizumab (Armstrong and Read, 2020; Ghoreschi et al, 2021), have revolutionized moderate-to-severe plaque psoriasis, the biologics are too expensive for ordinary patients. Mild-to-moderate plaque psoriatic patients are usually treated with topical therapies (glucocorticoids and vitamin D derivatives) or systemic medications (methotrexate, acitretin, and cyclosporine) (Armstrong and Read, 2020). Topical therapies or systemic medications have many contraindications or side effects (Boehncke and Schön, 2015; Reich et al, 2015). Seeking an economical, safe and effective treatment is extremely urgent for psoriasis
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