TY - JOUR
T1 - Cordycepin-enriched WIB-801C from Cordyceps militaris improves functional recovery by attenuating blood-spinal cord barrier disruption after spinal cord injury
AU - Lee, Jee Youn
AU - Choi, Hye Young
AU - Baik, Hyung Hwan
AU - Ju, Bong G.
AU - Kim, Won Ki
AU - Yune, Tae Young
N1 - Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (grant number: 2015R1A2A2A01003795, NRF-2016R1A6A3A11934000). All authors declare no conflict of interest.
Publisher Copyright:
© 2017 Elsevier Ireland Ltd
PY - 2017/5/5
Y1 - 2017/5/5
N2 - Ethnopharmacological relevance 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. Aim of this study 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). Materials and methods Male Sprague-Dawley rats were subjected to contusive SCI using a New York University (NYU) impactor, and WIB-801C (50 mg/kg) was administered at 2 h and 8 h 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. Conclusion Our results suggest that WIB-801C can be used as a therapeutic agent after SCI by attenuating BSCB disruption followed inflammation.
AB - Ethnopharmacological relevance 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. Aim of this study 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). Materials and methods Male Sprague-Dawley rats were subjected to contusive SCI using a New York University (NYU) impactor, and WIB-801C (50 mg/kg) was administered at 2 h and 8 h 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. Conclusion Our results suggest that WIB-801C can be used as a therapeutic agent after SCI by attenuating BSCB disruption followed inflammation.
KW - Apoptosis
KW - Blood-spinal cord barrier
KW - Cordycepin
KW - Matrix metalloprotease
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=85016283374&partnerID=8YFLogxK
U2 - 10.1016/j.jep.2017.03.047
DO - 10.1016/j.jep.2017.03.047
M3 - Article
C2 - 28363523
AN - SCOPUS:85016283374
SN - 0378-8741
VL - 203
SP - 90
EP - 100
JO - Journal of Ethnopharmacology
JF - Journal of Ethnopharmacology
ER -
