title: Cordycepin-enriched WIB-801C from Cordyceps militaris improves functional recovery by attenuating blood-spinal cord barrier disruption after spinal cord injury.
abstract: BACKGROUND
  Cordyceps militaris is an ingredient of traditional Chinese medicine and have been widely used for inflammatory diseases and cancer. Cordycepin is one of the major bioactive components of Cordyceps militaris, and has been known to have anti-inflammatory and anti-oxidant effects.
  
  
  OBJECTIVE
  In the present study, we examined whether WIB-801C, a standardized and cordycepin-enriched extract of caterpillar fungus (Cordyceps militaris), would attenuate blood-spinal cord barrier (BSCB) disruption by inhibiting matrix metalloprotease (MMP)-9 activity, leading to improvement of functional outcomes after spinal cord injury (SCI).
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to contusive SCI using a New York University (NYU) impactor, and WIB-801C (50mg/kg) was administered at 2h and 8h after injury orally and further treated once a day for indicated time points. BSCB disruption, MMP-9 activity, blood infiltration, inflammation, neuronal apoptosis, axonal loss, demyelination, and neurological deficit were evaluated.
  
  
  RESULTS
  We found that WIB-801C significantly attenuated BSCB disruption by inhibiting MMP-9 expression and activation after injury. The infiltration of neutrophils at 1 d and macrophage at 5 d after SCI was also ameliorated by WIB-801C as compared with vehicle control. In addition, the expression of inflammatory cytokines and mediators such as Tnf-α, IL-1β, IL-6, Cox-2, and inos as well as chemokines such as Gro-α and Mip-2α was significantly inhibited by WIB-801C. Furthermore, WIB-801C inhibits p38MAPK activation and proNGF production in microglia after injury. These events eventually led to the inhibition of apoptotic cell death of neurons and oligodendrocytes, improved functional recovery and attenuated demyelination and axon loss after SCI.
  
  
  CONCLUSIONS
  Our results suggest that WIB-801C can be used as a therapeutic agent after SCI by attenuating BSCB disruption followed inflammation.
authors.affiliation: Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: jeeyoun@khu.ac.kr.
authors.forename: Jee Youn
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: neuron@khu.ac.kr.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: hhbaik@khu.ac.kr.
authors.forename: Hyung Hwan
authors.initials: HH
authors.lastname: Baik
authors.affiliation: Department of Life Science, Sogang University, Seoul 04107, Republic of Korea. Electronic address: bgju@sogang.ac.kr.
authors.forename: Bong G
authors.initials: BG
authors.lastname: Ju
authors.affiliation: Department of Neuroscience, College of Medicine, Korea University, Seoul 02841, Republic of Korea. Electronic address: wonki@korea.ac.kr.
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Kim
authors.affiliation: Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: tyune@khu.ac.kr.
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Yune
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000473:pathology; D032661:Cordyceps / Q000737:chemistry*; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018836:Inflammation Mediators; D010936:Plant Extracts; C000605556:WIB801C; D020780:Matrix Metalloproteinase 9
keywords: Apoptosis; Blood-spinal cord barrier; Cordycepin; Matrix metalloprotease; Spinal cord injury