A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects.
BACKGROUND
Our previous in vitro results demonstrated that 11-dehydrosinulariolide significantly reduced 6-hydroxydopamine-induced cytotoxicity and apoptosis in a human neuroblastoma cell line, SH-SY5Y, and suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 in lipopolysaccharide-stimulated macrophage cells. The neuroprotective and anti-inflammatory effects of 11-dehydrosinulariolide may be suitable for treating spinal cord injury (SCI).


METHODS
In the present study, Wistar rats were pretreated with 11-dehydrosinulariolide or saline through intrathecal injection after a thoracic spinal cord contusion injury induced using a New York University (NYU) impactor. The apoptotic cells were assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression and localization of proinflammatory, apoptosis-associated and cell survival-related pathway proteins were examined through immunoblotting and immunohistochemistry.


RESULTS
11-Dehydrosinulariolide attenuated SCI-induced cell apoptosis by upregulating the antiapoptotic protein Bcl-2 and cell survival-related pathway proteins p-Akt and p-ERK, 8 h after SCI. Furthermore, the transcription factor p-CREB, which regulates Bcl-2 expression, was upregulated after 11-dehydrosinulariolide treatment. On day 7 after SCI, 11-dehydrosinulariolide exhibited an anti-inflammatory effect, attenuating SCI-induced upregulation of the inflammatory proteins iNOS and tumor necrosis factor-α. 11-Dehydrosinulariolide also induced an increase in the expression of arginase-1 and CD206, markers of M2 microglia, in the injured spinal cord on day 7 after SCI. Thus, the anti-inflammatory effect of 11-dehydrosinulariolide may be related to the promotion of an alternative pathway of microglia activation.


CONCLUSIONS
The results show that 11-dehydrosinulariolide exerts antiapoptotic effects at 8 h after SCI and anti-inflammatory effects at 7 days after SCI. We consider that this compound may be a promising therapeutic agent for SCI.
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. anubis0620@gmail.com.|Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei 11529, Taiwan. anubis0620@gmail.com.
Chun-Hong
CH
Chen
Division of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan. chen06688@gmail.com.|Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan. chen06688@gmail.com.
Nan-Fu
NF
Chen
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. qscjuejuejue@gmail.com.|Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei 11529, Taiwan. qscjuejuejue@gmail.com.
Chien-Wei
CW
Feng
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. joygetit@gmail.com.|Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei 11529, Taiwan. joygetit@gmail.com.
Shu-Yu
SY
Cheng
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. hanchun25@gmail.com.|Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei 11529, Taiwan. hanchun25@gmail.com.
Han-Chun
HC
Hung
Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan. khtsui60@gmail.com.|Department of Obstetrics and Gynecology and Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan. khtsui60@gmail.com.|Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung County 90741, Taiwan. khtsui60@gmail.com.
Kuan-Hao
KH
Tsui
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. hsuch@mail.nsysu.edu.tw.|Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. hsuch@mail.nsysu.edu.tw.
Chi-Hsin
CH
Hsu
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. pjsung@nmmba.gov.tw.|National Museum of Marine Biology & Aquarium, Pingtung 94450, Taiwan. pjsung@nmmba.gov.tw.|Graduate Institute of Marine Biology, National Dong Hwa University, Pingtung 94450, Taiwan. pjsung@nmmba.gov.tw.
Ping-Jyun
PJ
Sung
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. ma4949@cgmh.org.tw.|Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan. ma4949@cgmh.org.tw.
Wu-Fu
WF
Chen
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. wzh@mail.nsysu.edu.tw.|Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan. wzh@mail.nsysu.edu.tw.
Zhi-Hong
ZH
Wen
D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003288:Contusions / Q000188:drug therapy; D004224:Diterpenes / Q000737:chemistry / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D008124:Locomotion; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000523:psychology
C569844:11-dehydrosinulariolide; D000894:Anti-Inflammatory Agents, Non-Steroidal; D051017:Apoptosis Regulatory Proteins; D004224:Diterpenes; D018696:Neuroprotective Agents
11-dehydrosinulariolide; Sinularia flexibilis; anti-inflammation; marine natural compound; microglia; neuroprotection; spinal cord injury