Exp Neurobiol.  2010 Dec;19(3):146-154. 10.5607/en.2010.19.3.146.

Ethanol Extract of Bupleurum falcatum Improves Functional Recovery by Inhibiting Matrix Metalloproteinases-2 and -9 Activation and Inflammation after Spinal Cord Injury

• Lee JY
• Kim HS
• Oh TH
• Yune TY

• KMID: 1460759
• DOI: http://doi.org/10.5607/en.2010.19.3.146

Abstract

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade the extracellular matrix and other extracellular proteins. Upregulation of MMPs activity is known to be required for the inflammatory cell infiltration after spinal cord injury (SCI) and most likely contributes to early blood spinal barrier disruption and inflammation, thereby leading to the impairment of functional recovery. Here, we examined the effect of ethanol extract of Bupleurum falcatum (BF) on functional recovery by inhibiting MMP-2 and -9 activation and inflammation after SCI. Rats received a moderate, weight-drop contusion injury to spinal cord were administered orally with BF at a dose of 100 mg/kg for 14 d and functional recovery was measured by Basso-Beattie-Bresnahan locomotor open field behavioral rating test, inclined plane test and foot print analysis. To examine the neuroprotective effect of BF, TUNEL staining and counting were also performed. In addition, the expression and/or activation of MMP-2, MMP-9 and inflammatory mediators such as TNF-alpha, IL-1beta, COX-2, and iNOS were examined by RT-PCR and gelatin zymography using spinal cord tissue from 1 d after injury. Our data showed that BF significantly inhibited the expression and activation of both MMP-2 and MMP-9 after SCI. The mRNA expressions of TNF-alpha, IL-1beta, COX-2, and iNOS were also significantly attenuated by BF. Furthermore, BF reduced apoptotic cell death at 1 d after injury, thereby significantly reduced lesion volume and improved functional recovery. Taken together, these results suggest that BF can be used as a potential therapeutic agent for treating acute spinal injury.

Keyword

matrix metalloproteinase; spinal cord injury; blood brain barrier; zymography

MeSH Terms

Animals
Blood-Brain Barrier
Bupleurum
Cell Death
Contusions
Endopeptidases
Ethanol
Extracellular Matrix
Foot
Gelatin
In Situ Nick-End Labeling
Inflammation
Matrix Metalloproteinases
Neuroprotective Agents
Proteins
Rats
RNA, Messenger
Spinal Cord
Spinal Cord Injuries
Spinal Injuries
Tumor Necrosis Factor-alpha
Up-Regulation
Endopeptidases
Ethanol
Gelatin
Matrix Metalloproteinases
Neuroprotective Agents
Proteins
RNA, Messenger
Tumor Necrosis Factor-alpha