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 lipopolysa...
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MDPI AG
2016-09-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/14/9/160 |
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| author | Chun-Hong Chen Nan-Fu Chen Chien-Wei Feng Shu-Yu Cheng Han-Chun Hung Kuan-Hao Tsui Chi-Hsin Hsu Ping-Jyun Sung Wu-Fu Chen Zhi-Hong Wen |
| author_facet | Chun-Hong Chen Nan-Fu Chen Chien-Wei Feng Shu-Yu Cheng Han-Chun Hung Kuan-Hao Tsui Chi-Hsin Hsu Ping-Jyun Sung Wu-Fu Chen Zhi-Hong Wen |
| author_sort | Chun-Hong Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T22:31:54Z |
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| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T22:31:54Z |
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| series | Marine Drugs |
| spelling | doaj.art-46ee9499edf145fbbadfb421843471a22022-12-22T03:59:20ZengMDPI AGMarine Drugs1660-33972016-09-0114916010.3390/md14090160md14090160A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory EffectsChun-Hong Chen0Nan-Fu Chen1Chien-Wei Feng2Shu-Yu Cheng3Han-Chun Hung4Kuan-Hao Tsui5Chi-Hsin Hsu6Ping-Jyun Sung7Wu-Fu Chen8Zhi-Hong Wen9Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanDivision of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, TaiwanDoctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanDoctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanDoctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanDepartment of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, TaiwanDoctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanDepartment of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanDepartment of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanDoctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanBackground: 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.http://www.mdpi.com/1660-3397/14/9/160Sinularia flexibilismarine natural compound11-dehydrosinulariolidemicroglianeuroprotectionspinal cord injuryanti-inflammation |
| spellingShingle | Chun-Hong Chen Nan-Fu Chen Chien-Wei Feng Shu-Yu Cheng Han-Chun Hung Kuan-Hao Tsui Chi-Hsin Hsu Ping-Jyun Sung Wu-Fu Chen Zhi-Hong Wen A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects Marine Drugs Sinularia flexibilis marine natural compound 11-dehydrosinulariolide microglia neuroprotection spinal cord injury anti-inflammation |
| title | A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects |
| title_full | A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects |
| title_fullStr | A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects |
| title_full_unstemmed | A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects |
| title_short | A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects |
| title_sort | coral derived compound improves functional recovery after spinal cord injury through its antiapoptotic and anti inflammatory effects |
| topic | Sinularia flexibilis marine natural compound 11-dehydrosinulariolide microglia neuroprotection spinal cord injury anti-inflammation |
| url | http://www.mdpi.com/1660-3397/14/9/160 |
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