A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects
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Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan
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Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei 11529, Taiwan
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Division of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan
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Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
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Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
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Department of Obstetrics and Gynecology and Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan
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Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung County 90741, Taiwan
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Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan
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National Museum of Marine Biology & Aquarium, Pingtung 94450, Taiwan
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Graduate Institute of Marine Biology, National Dong Hwa University, Pingtung 94450, Taiwan
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Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editor: Keith B. Glaser
Mar. Drugs 2016, 14(9), 160; https://doi.org/10.3390/md14090160
Received: 14 June 2016 / Revised: 22 August 2016 / Accepted: 26 August 2016 / Published: 2 September 2016
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. Conclusion: 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.
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Keywords:
Sinularia flexibilis; marine natural compound; 11-dehydrosinulariolide; microglia; neuroprotection; spinal cord injury; anti-inflammation
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MDPI and ACS Style
Chen, C.-H.; Chen, N.-F.; Feng, C.-W.; Cheng, S.-Y.; Hung, H.-C.; Tsui, K.-H.; Hsu, C.-H.; Sung, P.-J.; Chen, W.-F.; Wen, Z.-H. A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects. Mar. Drugs 2016, 14, 160. https://doi.org/10.3390/md14090160
AMA Style
Chen C-H, Chen N-F, Feng C-W, Cheng S-Y, Hung H-C, Tsui K-H, Hsu C-H, Sung P-J, Chen W-F, Wen Z-H. A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects. Marine Drugs. 2016; 14(9):160. https://doi.org/10.3390/md14090160
Chicago/Turabian StyleChen, Chun-Hong; Chen, Nan-Fu; Feng, Chien-Wei; Cheng, Shu-Yu; Hung, Han-Chun; Tsui, Kuan-Hao; Hsu, Chi-Hsin; Sung, Ping-Jyun; Chen, Wu-Fu; Wen, Zhi-Hong. 2016. "A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects" Mar. Drugs 14, no. 9: 160. https://doi.org/10.3390/md14090160
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