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Daphnetin Ameliorates Experimental Autoimmune Encephalomyelitis Through Regulating Heme Oxygenase-1.
Neurochemical Research ( IF 3.7 ) Pub Date : 2020-01-16 , DOI: 10.1007/s11064-020-02960-0
Dan Wang 1 , Bo Zhu 2 , Xiaoyi Liu 2 , Qin Han 2 , Weihong Ge 3 , Wenping Zhang 1 , Yin Lu 4 , Qinan Wu 4 , Liyun Shi 2
Affiliation  

To assess the potential role of daphnetin, a clinically used anti-inflammatory agent, on the development of the inflammatory and neurodegenerative disease, we investigated its immune regulatory function in a murine model of experimental autoimmune encephalomyelitis (EAE). Significantly, lower levels of pro-inflammatory cytokines including interleukin (IL)-17, interferon-γ, Il6, Il12a, and Il23a were observed in brains of daphnetin-treated EAE mice, compared with those in control littermates. We also confirmed that daphnetin suppressed the production of IL-1β, IL-6, and tumor necrosis factor-α in lipopolysaccharide-stimulated mouse BV2 microglial cells. Mechanistically, heme oxygenase-1 (HO-1), a canonical anti-oxidant and anti-inflammatory factor, was found to be substantially induced by daphnetin treatment in BV2 cells. Also, a significantly higher level of HO-1, accompanied by a decreased level of malondialdehyde, was observed in daphnetin-treated EAE mice. More importantly, the deletion of HO-1 in BV2 microglia largely abrogated daphnetin-mediated inhibition of the inflammatory response. Together, our data demonstrate that daphnetin has an anti-inflammatory and neuroprotective role during the pathogenesis of EAE, which is partially at least, dependent on its regulation of HO-1.

中文翻译:

达芙妮通过调节血红素加氧酶-1改善实验性自身免疫性脑脊髓炎。

为了评估达芬肽(一种临床使用的消炎药)对炎症和神经退行性疾病发展的潜在作用,我们在实验性自身免疫性脑脊髓炎(EAE)的鼠模型中研究了其免疫调节功能。显着地,与对照组同窝出生的人相比,在用达啡肽治疗的EAE小鼠的大脑中观察到了较低的促炎细胞因子水平,包括白介素(IL)-17,干扰素-γ,Il6,Il12a和Il23a。我们还证实了蜂胶蛋白抑制了脂多糖刺激的小鼠BV2小胶质细胞中IL-1β,IL-6和肿瘤坏死因子-α的产生。从机理上讲,血红素加氧酶-1(HO-1)是一种典型的抗氧化剂和抗炎因子,被蜂胶素处理后在BV2细胞中基本上被诱导。也,在用达啡肽治疗的EAE小鼠中观察到HO-1的水平明显升高,同时丙二醛水平降低。更重要的是,BV2小胶质细胞中HO-1的缺失在很大程度上消除了蜂胶蛋白介导的炎症反应抑制作用。在一起,我们的数据表明,蜂胶蛋白在EAE的发病过程中具有抗炎和神经保护作用,这至少部分取决于其对HO-1的调节。
更新日期:2020-01-17
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