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Daphnetin Ameliorates Experimental Autoimmune Encephalomyelitis Through Regulating Heme Oxygenase-1

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Abstract

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.

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Acknowledgements

This work was supported by National Natural Scientific Funds (81770014, 81470210 and 81270066), the National Key Research and Development Program Project (2018YFC1705900), Natural Science Foundation of Zhejiang Province (LGF19H250002), Zhejiang Sci-Tech University scientific research fund (16042187-Y), and a project funded by the priority academic program development of Jiangsu higher education institutions.

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Authors and Affiliations

  1. Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, China

    Dan Wang & Wenping Zhang

  2. Department of Immunology and Medical Microbiology, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Bo Zhu, Xiaoyi Liu, Qin Han & Liyun Shi

  3. College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China

    Weihong Ge

  4. College of Pharmaceutical Science, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Yin Lu & Qinan Wu

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  1. Dan Wang
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Wang, D., Zhu, B., Liu, X. et al. Daphnetin Ameliorates Experimental Autoimmune Encephalomyelitis Through Regulating Heme Oxygenase-1. Neurochem Res 45, 872–881 (2020). https://doi.org/10.1007/s11064-020-02960-0

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