A Coral-Derived Compound Improves Functional Recovery after Spinal Cord Injury through Its Antiapoptotic and Anti-Inflammatory Effects

Abstract

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.

Metabolomic richness and fingerprints of deep-sea coral species and populations

“…They have been shown to be antimicrobial, anti-inflammatory, and toxic to cancer cell lines. Their functions in corals are diverse including predator deterrence, anti-fouling, and allelopathy (Aceret et al 1995 , 1998 ; Andrianasolo et al 2007 ; Chen et al 2016 ; Maida et al 1993 ; Sammarco and Coll 1990 ; Slattery et al 1998 ; Targett et al 1983 ; Zhang et al 2005 ). Thus, these diterpenes in C. delta may have a medically important function and deep-sea corals may be a source for many more marine natural products.…”

“…For example, terpenes and their derivatives have been the focus of marine products chemists for decades and 90% of known terpenic compounds produced by marine organisms are produced by cnidarians (Kornprobst 2014 ). Terpenes and their derivatives are involved in many functions in corals, including predator deterrence, anti-fouling and allelopathy, and exhibit medically useful properties such as being antimicrobial, anti-inflammatory and cytotoxic to cancer cell lines (Targett et al 1983 ; Sammarco and Coll 1990 ; Maida et al 1993 ; Aceret et al 1995 , 1998 ; Slattery et al 1998 ; Zhang et al 2005 ; Chen et al 2016 ). Other metabolites have been isolated from corals including caffeine, prostaglandins, natural nitrate esters and alcyopterosins, however the function and properties of many cnidarian compounds remains unknown (Bayer and Weinheimer 1974 ; Imre et al 1987 ; Palermo et al 2000 ).…”

Low frequency pulsed electromagnetic field promotes the recovery of neurological function after spinal cord injury in rats

“…SCI was avoided during the exposure of the T9‐T10 spinal cord. Next, SCI was performed using the 10 g NYU impactor (New York University, USA), which is widely used for the induction of SCI, dropped from a height of 4 cm to hit the center of the spinal cord at the T9‐T10 level. Afterwards, twitching of the hind limbs and movement of the tail could be observed, which indicated that the SCI was successfully induced.…”

Anti-Inflammatory and Antinociceptive Effects of Ethyl Acetate Fraction of an Edible Red Macroalgae Sarcodia ceylanica

“…Using a Leica DM-6000 CS microscope (Leica Instruments Inc., Wetzlar, Germany) with an Idea 5 MP CMOS digital camera system (SPOT Imaging Solutions, a division of Diagnostic Instruments, Inc., Sterling Heights, MI, USA) or a Xplorer Digital camera (SPOT Imaging Solutions), we analyzed all slides of the paw sections for histopathology and immunohistochemistry. With MetaMorph Imaging System software (Molecular Devices, Downington, PA, USA), we measured immunohistofluorescence data for individual pixel values of the immunoreactive-positive area by a modified method used in a previous study [ 47 ].…”