Glycyrrhizin reduces secondary inflammatory process after spinal cord compression injury in mice.
Glycyrrhizin, a major active constituent of liquorice root (Glycyrrhiza glabra), has a free radical scavenging property, and its effects were evaluated on an animal model of spinal cord injury (SCI) induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, tissue damage, and apoptosis (measured by terminal deoxynucleotidyltransferase-mediated dUTP-biotin end labeling staining, Bax, and Bcl-2 expression). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine, iNOS, and poly(adenosine diphosphate-ribose) in the spinal cord tissue. Additionally, we demonstrate that these inflammatory events were associated with the activation of nuclear factor-kappaB. In contrast, the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) nitrotyrosine and poly(adenosine diphosphate [ADP] ribose) formation, (3) iNOS expression, (4) nuclear factor-kappaB activation, and (5) apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP-biotin end labeling, Bax, and Bcl-2) was markedly reduced in spinal cord tissue obtained from mice treated with glycyrrhizin extract (10 mg/kg, i.p., 30 min before and 1 and 6 h after SCI). In a separate set of experiments, we have clearly demonstrated that glycyrrhizin extract treatment significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with glycyrrhizin 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.
Menegazzi
Marta
M
Mazzon
Emanuela
E
Crisafulli
Concetta
C
Di Paola
Rosanna
R
Dal Bosco
Martina
M
Zou
Zhenzhen
Z
Suzuki
Hisanori
H
Cuzzocrea
Salvatore
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D019695:Glycyrrhizic Acid / Q000627:therapeutic use*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C002744:3-nitrotyrosine; D014443:Tyrosine; D019695:Glycyrrhizic Acid; D052247:Nitric Oxide Synthase Type II