title: Corilagin Attenuates Radiation-Induced Brain Injury in Mice.
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.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Tong
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
authors.forename: Xican
authors.initials: X
authors.lastname: Gao
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wei
authors.affiliation: Experimental Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Dong
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. hustxiehe@hotmail.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. hustwhuh@126.com.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D047348:Hydrolyzable Tannins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011832:Radiation Injuries / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D016207:Cytokines; D005960:Glucosides; D047348:Hydrolyzable Tannins; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C049096:corilagin
keywords: Corilagin; NF-κB; Radiation-induced brain injury; STAT3