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Corilagin Attenuates Radiation-Induced Brain Injury in Mice

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Abstract

Cranial irradiation-induced inflammation plays a critical role in the initiation and progression of radiation-induced brain injury (RIBI). Anti-inflammation treatment may provide therapeutic benefits. Corilagin (beta-1-O-galloyl-3, 6-(R)-hexahydroxydiphenoyl-D-glucose, C27H22O18) was a novel member of the tannin family with anti-inflammatory properties and is isolated from some medicinal plants, such as Phyllanthus amarus and Caesalpinia coriaria. In this study, the effect of Corilagin on RIBI was investigated and the underlying mechanisms were explored. Spatial learning and memory ability of mice were investigated by the Morris water maze test. Evans blue leakage and electron microscopy were used to assess the integrity of blood-brain barrier (BBB). The mRNA and protein expressions of inflammatory cytokines, TNF-α and IL-1β, were measured by using real-time PCR and Western blotting. The activation of microglial cells and expression of TNF-α were examined by immunofluorescence staining. Phosphorylated signal transducers and activators of transcription 3 (p-STAT3) and IκBα, and the translocation of p65 from cytoplasm to nucleus were detected by using Western blotting. Morris water maze test showed that Corilagin ameliorated the neurocognitive deficits in RIBI mice. Evans blue leakage and electron microscopy exhibited that Corilagin partially protected the BBB integrity from cranial irradiation-caused damage; immunofluorescence staining showed that Corilagin could inhibit microglial activation and TNF-α expression. Real-time PCR and Western blotting revealed that Corilagin downregulated the expression of TNF-α and IL-1β and inhibited the irradiation-induced activation of NF-κB pathways by upregulating p-STAT3 expression. In conclusion, Corilagin could attenuate RIBI through inhibiting microglial activation and the expressions of inflammatory cytokines. Corilagin might inhibit the activation of NF-κB pathway in a STAT3-associated manner, thereby downregulating the inflammatory cytokine expressions.

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Acknowledgments

This study is sponsored by the National Nature Science Foundation of China (nos. 81172595 and 81573090), Post-doctoral Program foundation of China (no. 20100480905), and a grant from the Foundation of Special Post-doctoral Program of China (201104440).

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No potential conflicts of interest were disclosed.

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    Authors and Affiliations

    1. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China

      Fan Tong, Jian Zhang, Li Liu, Xican Gao, Qian Cai, Chunhua Wei, Gang Wu & Xiaorong Dong

    2. Experimental Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China

      Jihua Dong

    3. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China

      Yu Hu

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    1. Fan Tong
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    Fan Tong and Jian Zhang are considered co-first authors.

    Fan Tong and Jian Zhang contributed equally to this work.

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    Tong, F., Zhang, J., Liu, L. et al. Corilagin Attenuates Radiation-Induced Brain Injury in Mice. Mol Neurobiol 53, 6982–6996 (2016). https://doi.org/10.1007/s12035-015-9591-6

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