Background: Psoriasis is a chronic, immune-mediated inflammatory skin disease, and the inflammatory response plays an important role in its development and progression. Datura metel 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 Datura metel L. (EPD), which was verified by evaluations of the Psoriasis Area and Severity Index (PASI) score. Hematoxylin and eosin (H&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– myeloid differentiation primary response gene 88–nuclear Factor-κB–nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (TLR7/8–MyD88–NF-κB–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-1β, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and interferon-γ (IFN-γ). Besides, EPD decreased the imiquimod-induced expression levels of TLR7, TLR8, TRAF6, MyD88, p-IKKα, p-IKBα, p-NF-κB, NLRP3, apoptosis-associated speck-like protein contained a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase 1 (caspase-1), and IL-1β. 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–MyD88–NF-κb–NLRP3 inflammasome pathway.

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The 50% ethanol elution fractions of root-bark of Sambucus Williamsii Hance (rbSWH) evaluated the effect of proliferation and differentiation on preosteoblast MC3T3-E1 cell, and the mechanism of actions. We found that rbSWH(30, 60, and 90 µg/mL) can enhance cell proliferation by MTT assay and promote alkaline phosphatase (ALP) and bone Gla protein (BGP) activities, type I collagen (Col-I) synthesis, and mineralization nodule formation in primary cultured osteoblasts. The results showed that rbSWH can increase mRNA levels of BMP-2 and Runx2 using real-time reverse transcription-quantitative polymerase chain reaction, whereas the BMP-2 antagonist Noggin attenuated the increase of ALP activity induced by rbSWH, indicating that BMP-2 expression was required for the action of rbSWH in osteoblastic. We also found that rbSWH can enhance the expressions of BMP-2, BMPRIB, BMPRII, phosphorylation of Smad, JNK and p38, and Runx2 proteins by western blotting. In addition, pretreatment of cells with p38 inhibitor (SB203580) or JNK inhibitor (SP600125) can antagonize the elevation of BMP-2 expression, ALP activity, and cell viability induced by rbSWH. Taken together, our results provided an evidence that rbSWH can promote MC3T3-E1 cell proliferation and differentiation via BMP-2/Smad/p38/JNK/Runx2 signaling pathway.