2,4-Dimethoxy-6-Methylbenzene-1,3-diol, a Benzenoid From Antrodia cinnamomea, Mitigates Psoriasiform Inflammation by Suppressing MAPK/NF-κB Phosphorylation and GDAP1L1/Drp1 Translocation.
2,4-Dimethoxy-6-Methylbenzene-1,3-diol, a Benzenoid From Antrodia cinnamomea, Mitigates Psoriasiform Inflammation by Suppressing MAPK/NF-κB Phosphorylation and GDAP1L1/Drp1 Translocation.
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DOI：
10.3389/fimmu.2021.664425
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发表时间：
2021
影响因子：
7.3
通讯作者：
Fang JY
中科院分区：
文献类型：
--
作者：
Chuang SY;Chen CY;Yang SC;Alalaiwe A;Lin CH;Fang JY
牛樟芝具有抗炎、抗氧化和免疫调节活性。我们的目的是探索源自肉桂的 2,4-二甲氧基-6-甲基苯-1,3-二醇 (DMD) 的抗银屑病潜力。以咪喹莫特（IMQ）激活的巨噬细胞为细胞模型，检测DMD的体外抗炎作用。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 的显着高抑制。 DMD 处理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激活蛋白激酶 (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 DMD 干预对 GDAP1L1/Drp1 从细胞质到线粒体的易位的抑制。因此，线粒体裂变可能成为治疗银屑病炎症的新靶点。局部应用 DMD 后，经 IMQ 治疗的银屑病小鼠模型显示鳞屑、红斑和皮肤增厚减少。与仅 IMQ 刺激相比，活性化合物使表皮厚度减少约 2 倍。 DMD 减少了病变皮肤中浸润巨噬细胞和中性粒细胞的数量及其相关细胞因子/趋化因子的产生。 IMQ 处理皮肤的免疫染色表明 DMD 对 GDAP1LI 和磷酸化 Drp1 具有抑制作用。本研究提供了有关 DMD 作为银屑病炎症有效治疗方式的潜在用途的见解。
Antrodia cinnamomea exhibits anti-inflammatory, antioxidant, and immunomodulatory activities. We aimed to explore the antipsoriatic potential of 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 DMD in vitro. 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 DMD-treated 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 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 DMD. The present study provides insight regarding the potential use of DMD as an effective treatment modality for psoriatic inflammation.
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DOI：
10.1038/nrdp.2016.82
发表时间：
2016-11-24
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Greb, Jacqueline E;Goldminz, Ari M;Gottlieb, Alice B
通讯作者：
Gottlieb, Alice B
影响因子：
3.6
作者：
Damevska, Katerina;Neloska, Lence;Duma, Silvia
通讯作者：
Duma, Silvia
影响因子：
8
作者：
Chen, Chun-Yu;Lee, Ying-Hsuan;Hwang, Tsong-Long
通讯作者：
Hwang, Tsong-Long
影响因子：
6.1
作者：
Li, Leng;Zhang, Hong-yu;Han, Ling
通讯作者：
Han, Ling
影响因子：
3.2
作者：
Buccini, Marco;Punch, Kathryn A.;Piggott, Matthew J.
通讯作者：
Piggott, Matthew J.