Cudraxanthone D Ameliorates Psoriasis-like Skin Inflammation in an Imiquimod-Induced Mouse Model via Inhibiting the Inflammatory Signaling Pathways

Abstract

Psoriasis is a chronic inflammatory skin disease accompanied by excessive keratinocyte proliferation. Corticosteroids, vitamin D3 analogs, and calcineurin inhibitors, which are used to treat psoriasis, have diverse adverse effects, whereas natural products are popular due to their high efficiency and relatively low toxicity. The roots of the Cudrania tricuspidata (C. tricuspidata) are known to have diverse pharmacological effects, among which the anti-inflammatory effect is reported as a potential therapeutic agent in skin cells. Nevertheless, its effectiveness against skin diseases, especially psoriasis, is not fully elucidated. Here, we investigated the effect of cudraxanthone D (CD), extracted from the roots the C. tricuspidata Bureau, on psoriasis using an imiquimod (IMQ)-induced mouse model and the tumor necrosis factor (TNF)-α/interferon (IFN)-γ-activated keratinocytes. IMQ was topically applied to the back skin of C57BL/6 mice for seven consecutive days, and the mice were orally administered with CD. This resulted in reduced psoriatic characteristics, such as the skin thickness and Psoriasis Area Severity Index score, and the infiltration of neutrophils in IMQ-induced skin. CD inhibited the serum levels of TNF-α, immunoglobulin G2a, and myeloperoxidase, and the expression of Th1/Th17 cells in splenocytes. In TNF-α/IFN-γ-activated keratinocytes, CD reduced the expressions of CCL17, IL-1β, IL-6, and IL-8 by inhibiting the phosphorylation of STAT1 and the nuclear translocation of NF-kB. Taken together, these results suggest that CD could be a potential drug candidate for the treatment of psoriasis.

Classification and biomarker gene selection of pyroptosis-related gene expression in psoriasis using a random forest algorithm

“…Enhanced expression of IL-1β mRNA has been observed in vivo , in IMQ-induced mice ( Shou et al, 2021 ) ( Deng et al, 2019 ) ( Tang et al, 2021 ). This tendency was in accordance with the result of one previous cell experiment ( Kim et al, 2021 ). Aberrant or excessive activation of the classical caspase-1 path is associated with many autoinflammatory, autoimmune, and metabolic diseases ( Shi et al, 2015 ).…”

Platelet activation: a promoter for psoriasis and its comorbidity, cardiovascular disease

“…suggested that some of these IFN-induced transcripts (STAT1, IFIT1, and IFIT3) were key genes involved in psoriasis development ( 60 ). Higher levels of STAT1 were confirmed in psoriatic skin and STAT1 phosphorylation was increased following IFN-α or IFN-γ stimulation ( 61 – 65 ). In addition, Huang’s study revealed elevated levels of OAS1, OAS2, and OAS3 in psoriatic skin and serum and these IFN-induced enzymes decreased after biological therapies ( 66 ).…”

Natural Product-Derived Compounds Targeting Keratinocytes and Molecular Pathways in Psoriasis Therapeutics

“…Moreover, CD suppressed TNF-α, immunoglobulin G2a, and myeloperoxidase serum levels and inhibited Th1/Th17-cell expression in splenocytes. In TNF-α/IFN-γ-activated keratinocytes, CD suppressed inflammatory cytokine expression by modulating STAT1 phosphorylation and NF-kB nuclear translocation [ 113 ]. These findings highlight the potential of CD as a therapeutic candidate for managing psoriasis.…”