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Mar. Drugs 2012, 10(9), 1899-1919; doi:10.3390/md10091899
Article

Sinularin from Indigenous Soft Coral Attenuates Nociceptive Responses and Spinal Neuroinflammation in Carrageenan-Induced Inflammatory Rat Model

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Received: 12 June 2012; in revised form: 2 August 2012 / Accepted: 15 August 2012 / Published: 24 August 2012
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Abstract: Three decades ago, the marine-derived compound sinularin was shown to have anti-edematous effects on paw edema induced by carrageenan or adjuvant. To the best of our knowledge, no new studies were conducted to explore the bioactivity of sinularin until we reported the analgesic properties of sinularin based on in vivo experiments. In the present study, we found that sinularin significantly inhibits the upregulation of proinflammatory proteins, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) and upregulates the production of transforming growth factor-β (TGF-β) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells according to western blot analysis. We found that subcutaneous (s.c.) administration of sinularin (80 mg/kg) 1 h before carrageenan injection significantly inhibited carrageenan-induced nociceptive behaviors, including thermal hyperalgesia, mechanical allodynia, cold allodynia, and hindpaw weight-bearing deficits. Further, s.c. sinularin (80 mg/kg) significantly inhibited carrageenan-induced microglial and astrocyte activation as well as upregulation of iNOS in the dorsal horn of the lumbar spinal cord. Moreover, s.c. sinularin (80 mg/kg) inhibited carrageenan-induced tissue inflammatory responses, redness and edema of the paw, and leukocyte infiltration. The results of immunohistochemical studies indicate that s.c. sinularin (80 mg/kg) could upregulate production of TGF-β1 in carrageenan-induced inflamed paw tissue. The present results demonstrate that systemic sinularin exerts analgesic effects at the behavioral and spinal levels, which are associated with both inhibition of leukocyte infiltration and upregulation of TGF-β1.Three decades ago, the marine-derived compound sinularin was shown to have anti-edematous effects on paw edema induced by carrageenan or adjuvant. To the best of our knowledge, no new studies were conducted to explore the bioactivity of sinularin until we reported the analgesic properties of sinularin based on in vivo experiments. In the present study, we found that sinularin significantly inhibits the upregulation of proinflammatory proteins, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) and upregulates the production of transforming growth factor-β (TGF-β) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells according to western blot analysis. We found that subcutaneous (s.c.) administration of sinularin (80 mg/kg) 1 h before carrageenan injection significantly inhibited carrageenan-induced nociceptive behaviors, including thermal hyperalgesia, mechanical allodynia, cold allodynia, and hindpaw weight-bearing deficits. Further, s.c. sinularin (80 mg/kg) significantly inhibited carrageenan-induced microglial and astrocyte activation as well as upregulation of iNOS in the dorsal horn of the lumbar spinal cord. Moreover, s.c. sinularin (80 mg/kg) inhibited carrageenan-induced tissue inflammatory responses, redness and edema of the paw, and leukocyte infiltration. The results of immunohistochemical studies indicate that s.c. sinularin (80 mg/kg) could upregulate production of TGF-β1 in carrageenan-induced inflamed paw tissue. The present results demonstrate that systemic sinularin exerts analgesic effects at the behavioral and spinal levels, which are associated with both inhibition of leukocyte infiltration and upregulation of TGF-β1.
Keywords: sinularin; carrageenan; inflammatory pain; spinal neuroinflammation; transforming growth factor-β1; natural marine compound sinularin; carrageenan; inflammatory pain; spinal neuroinflammation; transforming growth factor-β1; natural marine compound
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Huang, S.-Y.; Chen, N.-F.; Chen, W.-F.; Hung, H.-C.; Lee, H.-P.; Lin, Y.-Y.; Wang, H.-M.; Sung, P.-J.; Sheu, J.-H.; Wen, Z.-H. Sinularin from Indigenous Soft Coral Attenuates Nociceptive Responses and Spinal Neuroinflammation in Carrageenan-Induced Inflammatory Rat Model. Mar. Drugs 2012, 10, 1899-1919.

AMA Style

Huang S-Y, Chen N-F, Chen W-F, Hung H-C, Lee H-P, Lin Y-Y, Wang H-M, Sung P-J, Sheu J-H, Wen Z-H. Sinularin from Indigenous Soft Coral Attenuates Nociceptive Responses and Spinal Neuroinflammation in Carrageenan-Induced Inflammatory Rat Model. Marine Drugs. 2012; 10(9):1899-1919.

Chicago/Turabian Style

Huang, Shi-Ying; Chen, Nan-Fu; Chen, Wu-Fu; Hung, Han-Chun; Lee, Hsin-Pai; Lin, Yen-You; Wang, Hui-Min; Sung, Ping-Jyun; Sheu, Jyh-Horng; Wen, Zhi-Hong. 2012. "Sinularin from Indigenous Soft Coral Attenuates Nociceptive Responses and Spinal Neuroinflammation in Carrageenan-Induced Inflammatory Rat Model." Mar. Drugs 10, no. 9: 1899-1919.


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