Cordycepin-enriched WIB-801C from Cordyceps militaris improves functional recovery by attenuating blood-spinal cord barrier disruption after spinal cord injury

Jee Youn Lee; Hye Young Choi; Hyung Hwan Baik; Bong G. Ju; Won Ki Kim; Tae Young Yune

doi:10.1016/j.jep.2017.03.047

Cordycepin-enriched WIB-801C from Cordyceps militaris improves functional recovery by attenuating blood-spinal cord barrier disruption after spinal cord injury

Jee Youn Lee, Hye Young Choi, Hyung Hwan Baik, Bong G. Ju, Won Ki Kim, Tae Young Yune

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	90-100
Number of pages	11
Journal	Journal of Ethnopharmacology
Volume	203
DOIs	https://doi.org/10.1016/j.jep.2017.03.047
Publication status	Published - 2017 May 5

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Ireland Ltd

Keywords

Apoptosis
Blood-spinal cord barrier
Cordycepin
Matrix metalloprotease
Spinal cord injury

ASJC Scopus subject areas

Pharmacology
Drug Discovery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jep.2017.03.047

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@article{bc8e6ed025214f9d93e0a5d160bf2b6c,

title = "Cordycepin-enriched WIB-801C from Cordyceps militaris improves functional recovery by attenuating blood-spinal cord barrier disruption after spinal cord injury",

abstract = "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.",

keywords = "Apoptosis, Blood-spinal cord barrier, Cordycepin, Matrix metalloprotease, Spinal cord injury",

author = "Lee, {Jee Youn} and Choi, {Hye Young} and Baik, {Hyung Hwan} and Ju, {Bong G.} and Kim, {Won Ki} and Yune, {Tae Young}",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Ireland Ltd",

year = "2017",

month = may,

day = "5",

doi = "10.1016/j.jep.2017.03.047",

language = "English",

volume = "203",

pages = "90--100",

journal = "Journal of Ethnopharmacology",

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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

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

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Cordycepin-enriched WIB-801C from Cordyceps militaris improves functional recovery by attenuating blood-spinal cord barrier disruption after spinal cord injury

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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