<i>Datura Metel</i> L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8–MyD88–NF-κB–NLRP3 Inflammasome Pathway

oleh: Bing-You Yang, Yan-Gang Cheng, Yan Liu, Yuan Liu, Jin-Yan Tan, Wei Guan, Shuang Guo, Hai-Xue Kuang

Format: Article
Diterbitkan: MDPI AG 2019-06-01

Deskripsi

Background: Psoriasis is a chronic, immune-mediated inflammatory skin disease, and the inflammatory response plays an important role in its development and progression. <i>Datura metel</i> L. is a traditional Chinese medicine that exhibited a significant therapeutic effect on psoriasis in our previous study due to its remarkable anti-inflammatory effect. Meanwhile, the mechanism underlying its effects on psoriasis is still unclear. Methods: An imiquimod-induced psoriasis-like dermatitis mouse model was constructed to evaluate the protective effect of the effective part of <i>Datura metel</i> L. (EPD), which was verified by evaluations of the Psoriasis Area and Severity Index (PASI) score. Hematoxylin and eosin (H&amp;E) staining, immunohistochemical examination, enzyme-linked immunosorbent assay (ELISA), and Western blot were used to measure the inflammatory cytokines and the protein expression associated with the Toll-like receptor 7&#8722; myeloid differentiation primary response gene 88&#8722;nuclear Factor-&#954;B&#8722;nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (TLR7/8&#8722;MyD88&#8722;NF-&#954;B&#8722;NLRP3) inflammasome pathway. Results: EPD significantly decreased the PASI, reduced epidermal thickness, and decreased the proliferation and differentiation of epidermal cells in psoriasis-like dermatitis C57BL/6 mice induced by imiquimod (IMQ). Furthermore, EPD reduced the infiltration of CD3+ cells to psoriatic lesions, as well as ameliorated the elevations of intercellular adhesion molecule 1 (ICAM-1) and inhibited the production of imiquimod-induced inflammatory cytokines, including IL-1&#946;, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, tumor necrosis factor-&#945; (TNF-&#945;), monocyte chemotactic protein 1 (MCP-1), and interferon-&#947; (IFN-&#947;). Besides, EPD decreased the imiquimod-induced expression levels of TLR7, TLR8, TRAF6, MyD88, p-IKK&#945;, p-IKB&#945;, p-NF-&#954;B, NLRP3, apoptosis-associated speck-like protein contained a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase 1 (caspase-1), and IL-1&#946;. Conclusion: This study demonstrated that EPD exhibited a protective effect on an imiquimod-induced psoriasis mice model by inhibiting the inflammatory response, which might be ascribed to the inhibition of the TLR7/8&#8722;MyD88&#8722;NF-&#954;b&#8722;NLRP3 inflammasome pathway.