Objectives: Inflammation and apoptosis play a critical role in the pathological progress of traumatic brain injury (TBI). Isoliquiritigenin is a bioactive component extracted from licorice roots, which possesses anti-inflammatory and anti-apoptotic properties. This study aims to investigate the potential effects of isoliquiritigenin on neuroinflammation in a rat model of TBI. Methods: The SH-SY5Y cells were subjected to cell injury induced by shear stress and the effect of isoliquiritigenin on cell apoptosis was measured. Male rats received a controlled cortical impact to induce TBI and were then treated with isoliquiritigenin (20 mg/kg). Brain edema and contusion volume were measured to assess brain damage. Morris water maze, the beam-balance test, and the beam-walk test were performed to evaluate the cognitive and motor functions. Results: Levels of proinflammatory cytokines and apoptotic regulators were measured. Results showed that isoliquiritigenin reduced shear stress-induced cell apoptosis in vitro. In young rats subjected to TBI, treatment of isoliquiritigenin reduced brain damage and attenuated motor and cognitive impairments. Isoliquiritigenin also reduced the level of proinflammatory cytokines and Bax and increased Bcl-2 and Bcl-xL in TBI rats. Conclusions: These findings suggest that isoliquiritigenin possesses beneficial effects in TBI by inhibiting inflammation and apoptosis.

1.
Popernack
ML
,
Gray
N
,
Reuter-Rice
K
: Moderate-to-severe traumatic brain injury in children: Complications and rehabilitation strategies. Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners
2015
;29:e1-7.
2.
Soares de Souza
R
,
Pessoa Pinheiro
P
,
Silva
JM
,
Neto
M
,
Ananias Machado Filho
J
: Traumatic brain injury (tbi): Morbidity, mortality and economic implications.
2015
.
3.
Alves
JL
.
Blood-brain barrier and traumatic brain injury
.
J Neurosci Res
.
2014
Feb
;
92
(
2
):
141
7
.
[PubMed]
0360-4012
4.
Morganti-Kossmann
MC
,
Rancan
M
,
Stahel
PF
,
Kossmann
T
.
Inflammatory response in acute traumatic brain injury: a double-edged sword
.
Curr Opin Crit Care
.
2002
Apr
;
8
(
2
):
101
5
.
[PubMed]
1070-5295
5.
Wong
J
,
Hoe
NW
,
Zhiwei
F
,
Ng
I
.
Apoptosis and traumatic brain injury
.
Neurocrit Care
.
2005
;
3
(
2
):
177
82
.
[PubMed]
1541-6933
6.
Cederberg
D
,
Siesjo
P
:
What has inflammation to do with traumatic brain injury?
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
2010
;26:221-226.
7.
Thal
SC
,
Neuhaus
W
.
The blood-brain barrier as a target in traumatic brain injury treatment
.
Arch Med Res
.
2014
Nov
;
45
(
8
):
698
710
.
[PubMed]
0188-4409
8.
Raghupathi
R
, I. Graham D, McIntosh T: Apoptosis after traumatic brain injury.
2000
.
9.
Peng
F
,
Du
Q
,
Peng
C
,
Wang
N
,
Tang
H
,
Xie
X
, et al.
A review: the pharmacology of isoliquiritigenin. Phytotherapy research
.
Phytother Res
.
2015
Jul
;
29
(
7
):
969
77
.
[PubMed]
0951-418X
10.
Li
W
,
Sun
YN
,
Yan
XT
,
Yang
SY
,
Kim
S
,
Lee
YM
, et al.
Flavonoids from Astragalus membranaceus and their inhibitory effects on LPS-stimulated pro-inflammatory cytokine production in bone marrow-derived dendritic cells
.
Arch Pharm Res
.
2014
Feb
;
37
(
2
):
186
92
.
[PubMed]
0253-6269
11.
Yang
EJ
,
Min
JS
,
Ku
HY
,
Choi
HS
,
Park
MK
,
Kim
MK
, et al.
Isoliquiritigenin isolated from Glycyrrhiza uralensis protects neuronal cells against glutamate-induced mitochondrial dysfunction
.
Biochem Biophys Res Commun
.
2012
May
;
421
(
4
):
658
64
.
[PubMed]
0006-291X
12.
Zeng
J
,
Chen
Y
,
Ding
R
,
Feng
L
,
Fu
Z
,
Yang
S
, et al.
Isoliquiritigenin alleviates early brain injury after experimental intracerebral hemorrhage via suppressing ROS- and/or NF-κB-mediated NLRP3 inflammasome activation by promoting Nrf2 antioxidant pathway
.
J Neuroinflammation
.
2017
Jun
;
14
(
1
):
119
.
[PubMed]
1742-2094
13.
Triyoso
DH
,
Good
TA
.
Pulsatile shear stress leads to DNA fragmentation in human SH-SY5Y neuroblastoma cell line
.
J Physiol
.
1999
Mar
;
515
(
Pt 2
):
355
65
.
[PubMed]
0022-3751
14.
Chen
T
,
Dai
SH
,
Jiang
ZQ
,
Luo
P
,
Jiang
XF
,
Fei
Z
, et al.
The ampar antagonist perampanel attenuates traumatic brain injury through anti-oxidative and anti-inflammatory activity
.
Cell Mol Neurobiol
.
2017
Jan
;
37
(
1
):
43
52
.
[PubMed]
0272-4340
15.
Maneshi
MM
,
Sachs
F
,
Zonglu Hua
S
:
A threshold shear force for calcium influx in an astrocyte model of traumatic brain injury.
2014
.
16.
Figaji
AA
.
Anatomical and physiological differences between children and adults relevant to traumatic brain injury and the implications for clinical assessment and care
.
Front Neurol
.
2017
Dec
;
8
:
685
.
[PubMed]
1664-2295
17.
Cheng
WH
,
Stukas
S
,
Martens
KM
,
Namjoshi
DR
,
Button
EB
,
Wilkinson
A
, et al.
Age at injury and genotype modify acute inflammatory and neurofilament-light responses to mild CHIMERA traumatic brain injury in wild-type and APP/PS1 mice
.
Exp Neurol
.
2018
Mar
;
301
Pt A
:
26
38
.
[PubMed]
0014-4886
18.
Kumar
A
,
Stoica
BA
,
Sabirzhanov
B
,
Burns
MP
,
Faden
AI
,
Loane
DJ
.
Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states
.
Neurobiol Aging
.
2013
May
;
34
(
5
):
1397
411
.
[PubMed]
0197-4580
19.
Sherer
M
,
Sander
AM
,
Nick
TG
,
Melguizo
MS
,
Tulsky
DS
,
Kisala
P
, et al.
Key dimensions of impairment, self-report, and environmental supports in persons with traumatic brain injury
.
Rehabil Psychol
.
2015
May
;
60
(
2
):
138
46
.
[PubMed]
0090-5550
20.
McIntyre
A
,
Mehta
S
,
Janzen
S
,
Aubut
J
,
Teasell
RW
.
A meta-analysis of functional outcome among older adults with traumatic brain injury
.
NeuroRehabilitation
.
2013
;
32
(
2
):
409
14
.
[PubMed]
1878-6448
21.
Hukkelhoven
CW
,
Steyerberg
EW
,
Rampen
AJ
,
Farace
E
,
Habbema
JD
,
Marshall
LF
, et al.
Patient age and outcome following severe traumatic brain injury: an analysis of 5600 patients
.
J Neurosurg
.
2003
Oct
;
99
(
4
):
666
73
.
[PubMed]
0022-3085
22.
Rodney
T
,
Osier
N
,
Gill
J
.
Pro- and anti-inflammatory biomarkers and traumatic brain injury outcomes: A review
.
Cytokine
.
2018
Oct
;
110
:
248
56
.
[PubMed]
1043-4666
23.
Lloyd
E
,
Somera-Molina
K
,
Van Eldik
LJ
,
Watterson
DM
,
Wainwright
MS
.
Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury
.
J Neuroinflammation
.
2008
Jun
;
5
(
1
):
28
.
[PubMed]
1742-2094
24.
Tehranian
R
,
Rose
ME
,
Vagni
V
,
Pickrell
AM
,
Griffith
RP
,
Liu
H
, et al.
Disruption of Bax protein prevents neuronal cell death but produces cognitive impairment in mice following traumatic brain injury
.
J Neurotrauma
.
2008
Jul
;
25
(
7
):
755
67
.
[PubMed]
0897-7151
25.
Wang
B
,
Han
S
.
Modified exosomes reduce apoptosis and ameliorate neural deficits induced by traumatic brain injury.
ASAIO journal (American Society for Artificial Internal Organs : 1992)
2018
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