Antrodia cinnamomea exhibits anti-inflammatory, antioxidant, and immunomodulatory activities. We aimed to explore the antipsoriatic potential of ethanolic extract (AC) and 2,4-dimethoxy-6-methylbenzene-1,3-diol (DMD) derived from A. cinnamomea. The macrophages activated by imiquimod (IMQ) were used as the cell model for examining the anti-inflammatory effect of AC and DMD in vitro. The heatmap of DNA microarray assay revealed a significant reduction of cytokines, chemokines, and GDAP1L1 in the activated macrophages after DMD treatment. A significantly high inhibition of IL-23 and IL-6 by DMD was observed in THP-1 macrophages and bone marrow-derived mouse macrophages. The conditioned medium of IMQ-stimulated macrophages could reduce neutrophil migration and keratinocyte overproliferation. DMD could downregulate cytokine/chemokine by suppressing the phosphorylation of mitogen-activated protein kinases (MAPKs) and NF-κB. We also observed inhibition of GDAP1L1/Drp1 translocation from the cytoplasm to mitochondria by DMD intervention. Thus, mitochondrial fission could be a novel target for treating psoriatic inflammation. A psoriasiform mouse model treated by IMQ showed reduced scaling, erythema, and skin thickening after topical application of AC and DMD. Compared to the IMQ stimulation only, the active compound decreased epidermal thickness by about 2-fold. DMD diminished the number of infiltrating macrophages and neutrophils and their related cytokine/chemokine production in the lesional skin. Immunostaining of the IMQ-treated skin demonstrated the inhibition of GDAP1LI and phosphorylated Drp1 by AC and DMD. The present study provides insight regarding the potential use of DMD as an effective treatment modality for psoriatic inflammation.

中文翻译：

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2,4-二甲氧基-6-甲基苯-1,3-二醇，一种来自牛樟芝的苯类，通过抑制巨噬细胞中的 MAPK/NF-κB 磷酸化和 GDAP1L1/Drp1 易位来减轻银屑病炎症

牛樟芝具有抗炎、抗氧化和免疫调节活性。我们旨在探索来自肉桂的乙醇提取物 (AC) 和 2,4-二甲氧基-6-甲基苯-1,3-二醇 (DMD) 的抗银屑病潜力。咪喹莫特 (IMQ) 激活的巨噬细胞被用作细胞模型，用于在体外检查 AC 和 DMD 的抗炎作用。DNA 微阵列分析的热图显示，DMD 治疗后活化巨噬细胞中的细胞因子、趋化因子和 GDAP1L1 显着减少。在 THP-1 巨噬细胞和骨髓来源的小鼠巨噬细胞中观察到 DMD 对 IL-23 和 IL-6 的显着抑制。IMQ 刺激的巨噬细胞的条件培养基可以减少中性粒细胞迁移和角质形成细胞过度增殖。DMD 可以通过抑制丝裂原活化蛋白激酶 (MAPK) 和 NF-κB 的磷酸化来下调细胞因子/趋化因子。我们还观察到通过 DMD 干预抑制 GDAP1L1/Drp1 从细胞质到线粒体的易位。因此，线粒体裂变可能是治疗银屑病炎症的新靶点。用 IMQ 治疗的银屑病小鼠模型在局部应用 AC 和 DMD 后显示出减少的鳞屑、红斑和皮肤增厚。与仅 IMQ 刺激相比，活性化合物将表皮厚度降低了约 2 倍。DMD 减少了浸润性巨噬细胞和中性粒细胞的数量以及它们在损伤皮肤中的相关细胞因子/趋化因子的产生。IMQ 处理过的皮肤的免疫染色表明 AC 和 DMD 抑制了 GDAP1LI 和磷酸化的 Drp1。