Efficacy of treatment with verbascoside, biotechnologically produced by Syringa vulgaris plant cell cultures in an experimental mice model of spinal cord trauma.
In this study we evaluated the effect of glycosylated phenylpropanoid verbascoside (VB), isolated from cultured cells of the medicinal plant Syringa vulgaris (Oleaceae) in experimental animal model of spinal cord injury (SCI). SCI was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, tissue damage, and apoptosis. At 1 and 6 h after injury, the mice were treated with VB extract, administered at the dose of 2 mg/kg with intraperitoneal administration. Immunohistochemical examination demonstrated a marked increase on expression for nitrotyrosine, inducible nitric oxide synthase, poly(ADP-ribose), and apoptosis events (increase of Bax and Bcl-2 expression) in the spinal cord tissue. Additionally, we demonstrate that these inflammatory events were associated with the cytokines expression (TNF-α and IL-1β), neutrophil infiltration (myeloperoxidase), and activation of NF-κB. In contrast, all of these parameters of inflammation were attenuated by treatment with VB. In a separate set of experiment, we have clearly demonstrated that VB treatment significantly ameliorated the recovery of function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with VB extract reduces the development of inflammation and tissue injury events associated with spinal cord trauma.
Genovese
Tiziana
T
IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.
Paterniti
Irene
I
Mazzon
Emanuela
E
Esposito
Emanuela
E
Di Paola
Rosanna
R
Galuppo
Maria
M
Bramanti
Placido
P
Cuzzocrea
Salvatore
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005960:Glucosides / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010636:Phenols / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D013116:Spinal Cord / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D031662:Syringa / Q000737:chemistry* / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D059808:Polyphenols
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005960:Glucosides; D053583:Interleukin-1beta; D052247:Nitric Oxide Synthase Type II; D010636:Phenols; D010936:Plant Extracts; D011064:Poly Adenosine Diphosphate Ribose; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D051028:bcl-2-Associated X Protein; C494827:Bax protein, mouse; C052617:Bcl2 protein, mouse; C002744:3-nitrotyrosine; C058956:acteoside; D059808:Polyphenols
Neuroreport. 2005 May 12;16(7):737-40
15858416
J Neurotrauma. 2007 Jun;24(6):991-9
17600515
J Neurosurg Spine. 2004 Oct;1(3):311-21
15478370
Brain Res Mol Brain Res. 2004 May 19;124(2):188-98
15135227
Eur J Pharm Sci. 2000 Apr;10(2):111-7
10727876
Neurosurgery. 1999 May;44(5):1027-39; discussion 1039-40
10232536
J Neurochem. 1995 May;64(5):1965-72
7722484
Prog Brain Res. 2002;137:37-47
12440358
J Pharmacol Exp Ther. 2005 Jul;314(1):53-60
15784653
J Neurosurg. 1991 Jul;75(1):15-26
2045903
Prog Clin Biol Res. 1989;301:39-51
2678130
Amino Acids. 2003 Dec;25(3-4):295-311
14661092
Cell Mol Biol (Noisy-le-grand). 2007 Apr 15;53(1):15-25
17519109
Pharmacol Res. 2007 Apr;55(4):335-42
17292620
Trends Pharmacol Sci. 1999 Apr;20(4):171-81
10322503
Acta Neurochir Suppl. 2003;86:407-13
14753477
Nature. 1995 Apr 20;374(6524):733-6
7715730
J Neurochem. 1999 Jul;73(1):205-13
10386972
Biochem Soc Symp. 2004;(71):107-20
15777016
Ann Rheum Dis. 2004 Nov;63 Suppl 2:ii57-ii61
15479873
J Immunol. 1993 Aug 15;151(4):2132-41
8102159
Pharmacol Res. 2005 Jul;52(1):109-18
15911339
Biochem Pharmacol. 2000 Jan 1;59(1):13-23
10605930
J Comp Neurol. 2007 Jan 10;500(2):267-85
17111361
Pharmacol Rev. 2001 Mar;53(1):135-59
11171943
Acta Neurol Scand. 1989 Jun;79(6):460-7
2782026
J Neurotrauma. 2006 May;23(5):635-59
16689667
Cell Signal. 2002 Nov;14(11):879-97
12220615
J Neurosci Res. 1999 Mar 1;55(5):542-56
10082077
Nature. 1998 Jan 22;391(6665):393-7
9450756
J Neurosci Res. 2003 May 15;72(4):508-19
12704812
J Neurochem. 2007 Feb;100(3):639-49
17181549
J Neurotrauma. 2004 Sep;21(9):1255-63
15453994
J Neurosci. 2001 Jul 1;21(13):4649-56
11425892
J Neurotrauma. 2005 Oct;22(10):1123-33
16238488
J Biol Chem. 2005 Jul 29;280(30):27888-95
15944151
Biotechniques. 1994 Jun;16(6):1126-8
8074880
J Neurosurg Spine. 2006 Feb;4(2):145-53
16506482
J Immunol. 1999 Nov 1;163(9):5094-104
10528216
Biochem Soc Trans. 2006 Nov;34(Pt 5):965-70
17052238
J Pharmacol Exp Ther. 2006 Mar;316(3):1006-16
16303916
Brain Pathol. 1995 Oct;5(4):407-13
8974623