6-Shogaol is one of the main active phenolic components of ginger and has neuroprotective effects by protecting brain against the oxidative stress and regulate the levels of neurotrophic factors. The objective of the present study was to verify the effect of 6-shogaol on neurochemical parameters in offspring after maternal immune activation by lipopolysaccharide (LPS) in rats. Twelve pregnant Wistar rats received 100 μg/kg of LPS or saline solution on the gestational day 9.5. Male offspring participated in the study and from the postnatal days (PND) 30 and 55, respectively, they were supplemented with 6-shogaol or saline solution, by gavage at a dose of 10 mg/kg/day, orally for 5 days. In PND 37 and 62, analysis of kinase signaling regulated by extracellular signal 1/2 (ERK 1/2), levels of neurotrophic factor derived from the brain (BDNF), and neuron-specific enolase (NSE), lipid and protein oxidative damage was evaluated by 4-hydroxy-2-nonenal (HNE) and 3-nitrotyrosine (3-NT), respectively, and myeloperoxidase (MPO) activity was performed in the hippocampus. Prenatal exposure to LPS significantly decreased ERK and BDNF levels in PND 37 and 62, increased NSE levels and lipid damage in rats in PND 37, and increased 3-NT level in rats in PND 62. With treatment using 6-shogaol, an increase in ERK and BDNF levels was identified in PND 37 and 62 and a reduction in HNE and MPO activity in rats in PND 37 and 62, respectively. 6-Shogaol positively increased markers of neuronal growth, plasticity and synaptic activity and reduced oxidative damage in the hippocampus in an animal model of autism by maternal immune activation.

1.
Ha
SK
,
Moon
E
,
Ju
MS
,
Kim
DH
,
Ryu
JH
,
Oh
MS
,
6-Shogaol, a ginger product, modulates neuroinflammation: a new approach to neuroprotection
.
Neuropharmacology
.
2012 Aug
;
63
(
2
):
211
23
. .
2.
Li
Y
,
Hong
Y
,
Han
Y
,
Wang
Y
,
Xia
L
.
Chemical characterization and antioxidant activities comparison in fresh, dried, stir-frying and carbonized ginger
.
J Chromatogr B Analyt Technol Biomed Life Sci
.
2016 Feb
;
1011
:
223
32
. .
3.
Mashhadi
NS
,
Ghiasvand
R
,
Askari
G
,
Hariri
M
,
Darvishi
L
,
Mofid
MR
.
Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence
.
Int J Prev Med
.
2013 Apr
;
4
(
Suppl 1
):
S36
42
.
4.
Suekawa
M
,
Ishige
A
,
Yuasa
K
,
Sudo
K
,
Aburada
M
,
Hosoya
E
.
Pharmacological studies on ginger. I. Pharmacological actions of pungent constituents, (6)-gingerol and (6)-shogaol
.
J Pharmacobiodyn
.
1984
;
7
(
11
):
836
48
.
5.
Nagendra chari
KL
,
Manasa
D
,
Srinivas
P
,
Sowbhagya
HB
.
Enzyme-assisted extraction of bioactive compounds from ginger (Zingiber officinale Roscoe)
.
Food Chem
.
2013 Aug
;
139
(
1–4
):
509
14
. .
6.
Saxena
R
,
Rida
PC
,
Kucuk
O
,
Aneja
R
.
Ginger augmented chemotherapy: a novel multitarget nontoxic approach for cancer management
.
Mol Nutr Food Res
.
2016 Jun
;
60
(
6
):
1364
73
. .
7.
Kim
S
,
Kwon
J
.
[6]-shogaol attenuates neuronal apoptosis in hydrogen peroxide-treated astrocytes through the up-regulation of neurotrophic factors
.
Phytother Res
.
2013 Dec
;
27
(
12
):
1795
9
. .
8.
Gaire
BP
,
Kwon
OW
,
Park
SH
,
Chun
KH
,
Kim
SY
,
Shin
DY
,
Neuroprotective effect of 6-paradol in focal cerebral ischemia involves the attenuation of neuroinflammatory responses in activated microglia
.
PLoS One
.
2015 Mar
;
10
(
3
):
e0120203
. .
9.
Moon
M
,
Kim
HG
,
Choi
JG
,
Oh
H
,
Lee
PK
,
Ha
SK
,
6-shogaol, an active constituent of ginger, attenuates neuroinflammation and cognitive deficits in animal models of dementia
.
Biochem Biophys Res Commun
.
2014 Jun
;
449
(
1
):
8
13
. .
10.
Park
G
,
Kim
HG
,
Ju
MS
,
Ha
SK
,
Park
Y
,
Kim
SY
,
6-shogaol, an active compound of ginger, protects dopaminergic neurons in Parkinson’s disease models via anti-neuroinflammation
.
Acta Pharmacol Sin
.
2013 Sep
;
34
(
9
):
1131
9
. .
11.
Banks
WA
.
The blood-brain barrier in neuroimmunology: tales of separation and assimilation
.
Brain Behav Immun
.
2015 Feb
;
44
:
1
8
. .
12.
Lucchina
L
,
Depino
AM
.
Altered peripheral and central inflammatory responses in a mouse model of autism
.
Autism Res
.
2014 Apr
;
7
(
2
):
273
89
. .
13.
Kanner
L
.
Autistic disturbances of affective contact
.
Nerv Child
.
1943
;
2
:
217
50
.
14.
Brasil. Linha de cuidado para a atenção às pessoas com transtornos do espectro do autismo e suas famílias na Rede de Atenção Psicossocial do Sistema Único de Saúde. Brasília, DF: Ministério da Saúde; 2013.
15.
Blumberg
SJ
,
Bramlett
MD
,
Kogan
MD
,
Schieve
LA
,
Jones
JR
,
Lu
MC
.
Changes in prevalence of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011–2012
.
Natl Health Stat Report
.
2013 Mar
;
20
(
65
):
1
11
.
16.
Brigandi
SA
,
Shao
H
,
Qian
SY
,
Shen
Y
,
Wu
BL
,
Kang
JX
.
Autistic children exhibit decreased levels of essential fatty acids in red blood cells
.
Int J Mol Sci
.
2015 May
;
16
(
12
):
10061
76
. .
17.
Hampson
DR
,
Blatt
GJ
.
Autism spectrum disorders and neuropathology of the cerebellum
.
Front Neurosci
.
2015 Nov
;
9
:
420
. .
18.
Bernardi
MM
,
Kirsten
TB
,
Trindade
MO
.
Sobre o autismo, neuroinflamação e modelos animais para o estudo de autismo
.
Rev Neurociências
.
2012 Mar
;
20
(
1
):
117
27
.
19.
Rose
D
,
Ashwood
P
.
Potential cytokine biomarkers in autism spectrum disorders
.
Biomark Med
.
2014 Oct
;
8
(
9
):
1171
81
. .
20.
Levy
SE
,
Hyman
SL
.
Complementary and alternative medicine treatments for children with autism spectrum disorders
.
Child Adolesc Psychiatr Clin N Am
.
2015 Jan
;
24
(
1
):
117
43
. .
21.
Brasil. Diretriz brasileira para o cuidado e a utilização de animais para fins científicos e didáticos [Internet]. 2016;5.
22.
Held
HE
,
Pilla
R
,
Ciarlone
GE
,
Landon
CS
,
Dean
JB
.
Female rats are more susceptible to central nervous system oxygen toxicity than male rats
.
Physiol Rep
.
2014 Apr
;
2
(
4
):
e00282
. .
23.
Cora
MC
,
Kooistra
L
,
Travlos
G
.
Vaginal cytology of the laboratory rat and mouse: review and criteria for the staging of the estrous cycle using stained vaginal smears
.
Toxicol Pathol
.
2015 Aug
;
43
(
6
):
776
93
. .
24.
Spencer
SJ
,
Mouihate
A
,
Galic
MA
,
Ellis
SL
,
Pittman
QJ
.
Neonatal immune challenge does not affect body weight regulation in rats
.
Am J Physiol Regul Integr Comp Physiol
.
2007 Aug
;
293
(
2
):
R581
9
. .
25.
Kirsten
TB
,
Taricano
M
,
Maiorka
PC
,
Palermo-Neto
J
,
Bernardi
MM
.
Prenatal lipopolysaccharide reduces social behavior in male offspring
.
Neuroimmunomodulation
.
2010
;
17
(
4
):
240
51
. .
26.
Cysneiros
RM
,
Ferrari
D
,
Arida
RM
,
Terra
VC
,
de Almeida
AC
,
Cavalheiro
EA
,
Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids
.
Epilepsy Behav
.
2010 Jan
;
17
(
1
):
33
8
. .
27.
László
A
,
Novák
Z
,
Szőllősi-Varga
I
,
Hai
du Q
,
Vetró
Á
,
Kovács
A
.
Blood lipid peroxidation, antioxidant enzyme activities and hemorheological changes in autistic children
.
Ideggyogy Sz
.
2013 Jan
;
66
(
1–2
):
23
8
.
28.
Nemec
M
,
Kaufman
L
,
Stump
D
,
Lindström
P
,
Varsho
B
,
Holson
J
.
Significance, reliability, and interpretation of developmental and reproductive toxicity study findings
. In:
Hood
RD
, editor.
Developmental and reproductive toxicology
.
Informa Healthcare
;
2005
. p.
329
424
. .
29.
Fortunato
JJ
,
da Rosa
N
,
Martins Laurentino
AO
,
Goulart
M
,
Michalak
C
,
Borges
LP
,
Effects of ω-3 fatty acids on stereotypical behavior and social interactions in Wistar rats prenatally exposed to lipopolysaccarides
.
Nutrition
.
2017 Mar
;
35
:
119
27
. .
30.
Lowry
OH
,
Rosebrough
NJ
,
Farr
AL
,
Randall
RJ
.
Protein measurement with the Folin phenol reagent
.
J Biol Chem
.
1951
;
193
(
1
):
265
75
. .
31.
Lim
S
,
Moon
M
,
Oh
H
,
Kim
HG
,
Kim
SY
,
Oh
MS
.
Ginger improves cognitive function via NGF-induced ERK/CREB activation in the hippocampus of the mouse
.
J Nutr Biochem
.
2014 Oct
;
25
(
10
):
1058
65
. .
32.
Joshi
G
,
Perluigi
M
,
Sultana
R
,
Agrippino
R
,
Calabrese
V
,
Butterfield
DA
.
In vivo protection of synaptosomes by ferulic acid ethyl ester (FAEE) from oxidative stress mediated by 2,2-azobis(2-amidino-propane)dihydrochloride (AAPH) or Fe2+/H2O2: insight into mechanisms of neuroprotection and relevance to oxidative stress-related
.
Neurochem Int
.
2006 Mar
;
48
(
4
):
318
27
.
33.
Sultana
R
,
Ravagna
A
,
Mohmmad-Abdul
H
,
Calabrese
V
,
Butterfield
DA
.
Ferulic acid ethyl ester protects neurons against amyloid beta- peptide(1-42)-induced oxidative stress and neurotoxicity: relationship to antioxidant activity
.
J Neurochem
.
2005 Feb
;
92
(
4
):
749
58
. .
34.
Bradley
PP
,
Christensen
RD
,
Rothstein
G
.
Cellular and extracellular myeloperoxidase in pyogenic inflammation
.
Blood
.
1982 Sep
;
60
(
3
):
618
22
. .
35.
Barichello
T
,
Generoso
JS
,
Goularte
JA
,
Collodel
A
,
Pitcher
MRRP
,
Simões
LR
,
Does infection-induced immune activation contribute to dementia?
Aging Dis
.
2015
;
6
(
5
):
342
. .
36.
Shim
S
,
Kim
S
,
Kwon
YB
,
Kwon
J
.
Protection by [6]-shogaol against lipopolysaccharide-induced toxicity in murine astrocytes is related to production of brain-derived neurotrophic factor
.
Food Chem Toxicol
.
2012 Mar
;
50
(
3–4
):
597
602
. .
37.
Zhou
S-F
,
Qiu
J
,
Zhou
Z-W
,
He
Z
,
Zhang
X
,
Zhu
S
.
Estimation of the binding modes with important human cytochrome P450 enzymes, drug interaction potential, pharmacokinetics, and hepatotoxicity of ginger components using molecular docking, computational, and pharmacokinetic modeling studies
.
Drug Des Devel Ther
.
2015 Feb
;
9
:
841
66
.
38.
Meltzer
A
,
Van de Water
J
.
The role of the immune system in autism spectrum disorder
.
Neuropsychopharmacology
.
2017 Jan
;
42
(
1
):
284
98
. .
39.
Skaper
SD
.
Neurotrophic factors: an overview
.
Methods Mol Biol
.
2018
;
1727
:
1
17
. .
40.
Autry
AE
,
Monteggia
LM
.
Brain-derived neurotrophic factor and neuropsychiatric disorders
.
Pharmacol Rev
.
2012 Apr
;
64
(
2
):
238
58
. .
41.
Perito
MES
,
Fortunato
JJ
.
Marcadores biológicos da depressão: uma revisão sobre a expressão de fatores neurotróficos
.
Rev Neurociências
.
2012 Mar
;
20
(
4
):
597
603
.
42.
Kasarpalkar
NJ
,
Kothari
ST
,
Dave
UP
.
Brain-derived neurotrophic factor in children with autism spectrum disorder
.
Ann Neurosci
.
2014 Oct
;
21
(
4
):
129
. .
43.
Leal
G
,
Comprido
D
,
Duarte
CB
.
BDNF-induced local protein synthesis and synaptic plasticity
.
Neuropharmacology
.
2014 Jan
;
76 Pt C
:
639
56
. .
44.
Francis
K
,
Dougali
A
,
Sideri
K
,
Kroupis
C
,
Vasdekis
V
,
Dima
K
,
Brain-derived neurotrophic factor (BDNF) in children with ASD and their parents: a 3-year follow-up
.
Acta Psychiatr Scand
.
2018 May
;
137
(
5
):
433
41
. .
45.
Castrén
E
,
Kojima
M
.
Brain-derived neurotrophic factor in mood disorders and antidepressant treatments
.
Neurobiol Dis
.
2017 Jan
;
97
:
119
26
. .
46.
Sangiovanni
E
,
Brivio
P
,
Dell'Agli
M
,
Calabrese
F
.
Botanicals as modulators of neuroplasticity: focus on BDNF
.
Neural Plast
.
2017
;
2017
:
5965371
19
. .
47.
Schroeter
ML
,
Abdul-Khaliq
H
,
Krebs
M
,
Diefenbacher
A
,
Blasig
IE
.
Neuron-specific enolase is unaltered whereas S100B is elevated in serum of patients with schizophrenia – original research and meta-analysis
.
Psychiatry Res
.
2009 May
;
167
(
1–2
):
66
72
. .
48.
Ogundele
OM
,
Omoaghe
AO
,
Ajonijebu
DC
,
Ojo
AA
,
Fabiyi
TD
,
Olajide
OJ
,
Glia activation and its role in oxidative stress
.
Metab Brain Dis
.
2014 Jun
;
29
(
2
):
483
93
. .
49.
Kelen
D
,
Andorka
C
,
Szabó
M
,
Alafuzoff
A
,
Kaila
K
,
Summanen
M
.
Serum copeptin and neuron specific enolase are markers of neonatal distress and long-term neurodevelopmental outcome
.
PLoS One
.
2017 Sep
;
12
(
9
):
e0184593
. .
50.
Züngün
C
,
Yilmaz
FM
,
Tutkun
E
,
Yilmaz
H
,
Uysal
S
.
Assessment of serum S100B and neuron specific enolase levels to evaluate the neurotoxıc effects of organıc solvent exposure
.
Clin Toxicol
.
2013 Sep
;
51
(
8
):
748
51
. .
51.
Elbassuoni
EA
,
Nazmy
WH
.
Novel neuroprotective role of hydrogen sulfide in a rat model of stress brain injury
.
Gen Physiol Biophys
.
2018
;
37
(
2
):
233
41
. .
52.
Onore
CE
,
Schwartzer
JJ
,
Careaga
M
,
Berman
RF
,
Ashwood
P
.
Maternal immune activation leads to activated inflammatory macrophages in offspring
.
Brain Behav Immun
.
2014 May
;
38
:
220
6
. .
53.
Bharath
S
,
Hsu
M
,
Kaur
D
,
Rajagopalan
S
,
Andersen
JK
.
Glutathione, iron and Parkinson’s disease
.
Biochem Pharmacol
.
2002 Sep
;
64
(
5–6
):
1037
48
. .
54.
Thiruchelvam
M
,
Prokopenko
O
,
Cory-Slechta
DA
,
Richfield
EK
,
Buckley
B
,
Mirochnitchenko
O
.
Overexpression of superoxide dismutase or glutathione peroxidase protects against the paraquat + maneb-induced Parkinson disease phenotype
.
J Biol Chem
.
2005 Jun
;
280
(
23
):
22530
9
. .
55.
Ling
ZD
,
Chang
Q
,
Lipton
JW
,
Tong
CW
,
Landers
TM
,
Carvey
PM
.
Combined toxicity of prenatal bacterial endotoxin exposure and postnatal 6-hydroxydopamine in the adult rat midbrain
.
Neuroscience
.
2004 Jan
;
124
(
3
):
619
28
. .
56.
Gundala
SR
,
Mukkavilli
R
,
Yang
C
,
Yadav
P
,
Tandon
V
,
Vangala
S
,
Enterohepatic recirculation of bioactive ginger phytochemicals is associated with enhanced tumor growth-inhibitory activity of ginger extract
.
Carcinogenesis
.
2014 Jun
;
35
(
6
):
1320
9
. .
57.
Oboh
G
,
Ademiluyi
AO
,
Akinyemi
AJ
.
Inhibition of acetylcholinesterase activities and some pro-oxidant induced lipid peroxidation in rat brain by two varieties of ginger (Zingiber officinale)
.
Exp Toxicol Pathol
.
2012 May
;
64
(
4
):
315
9
. .
58.
Jiménez-Escrig
A
,
Jiménez-Jiménez
I
,
Sánchez-Moreno
C
,
Saura-Calixto
F
.
Evaluation of free radical scavenging of dietary carotenoids by the stable radical 2,2-diphenyl-1-picrylhydrazyl
.
J Sci Food Agric
.
2000 Jul
;
80
(
11
):
1686
90
. .
59.
Boksa
P
.
Effects of prenatal infection on brain development and behavior: a review of findings from animal models
.
Brain Behav Immun
.
2010 Aug
;
24
(
6
):
881
97
. .
60.
Dröge
W
.
Free radicals in the physiological control of cell function
.
Physiol Rev
.
2002 Jan
;
82
(
1
):
47
95
. .
61.
Green
PS
,
Mendez
AJ
,
Jacob
JS
,
Crowley
JR
,
Growdon
W
,
Hyman
BT
,
Neuronal expression of myeloperoxidase is increased in Alzheimer’s disease
.
J Neurochem
.
2004 Aug
;
90
(
3
):
724
33
. .
62.
Choi
DK
,
Pennathur
S
,
Perier
C
,
Tieu
K
,
Teismann
P
,
Wu
DC
,
Ablation of the inflammatory enzyme myeloperoxidase mitigates features of Parkinson’s disease in mice
.
J Neurosci
.
2005 Jul
;
25
(
28
):
6594
600
. .
63.
Nagra
RM
,
Becher
B
,
Tourtellotte
WW
,
Antel
JP
,
Gold
D
,
Paladino
T
,
Immunohistochemical and genetic evidence of myeloperoxidase involvement in multiple sclerosis
.
J Neuroimmunol
.
1997 Sep
;
78
(
1–2
):
97
107
. .
64.
Russo
AJ
.
Decreased plasma myeloperoxidase associated with probiotic therapy in autistic children
.
Clin Med Insights Pediatr
.
2015 Jan
;
9
:
13
. .
65.
Ezzat
SM
,
Ezzat
MI
,
Okba
MM
,
Menze
ET
,
Abdel-Naim
AB
.
The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity
.
J Ethnopharmacol
.
2018 Mar
;
214
:
113
23
.
66.
Goh
S
,
Dong
Z
,
Zhang
Y
,
DiMauro
S
,
Peterson
BS
.
Mitochondrial dysfunction as a neurobiological subtype of autism spectrum disorder: evidence from brain imaging
.
JAMA Psychiatry
.
2014 Jun
;
71
(
6
):
665
. .
67.
Supekar
K
,
Menon
V
.
Sex differences in structural organization of motor systems and their dissociable links with repetitive/restricted behaviors in children with autism
.
Mol Autism
.
2015 Dec
;
6
(
1
):
50
. .
68.
Schendel
DE
,
Grønborg
TK
,
Parner
ET
.
The genetic and environmental contributions to autism: looking beyond twins
.
JAMA
.
2014 May
;
311
(
17
):
1738
. .
69.
Kim
SY
,
Choi
US
,
Park
SY
,
Oh
SH
,
Yoon
HW
,
Koh
YJ
,
Abnormal activation of the social brain network in children with autism spectrum disorder: an fMRI Study
.
Psychiatry Investig
.
2015
;
12
(
1
):
37
. .
70.
Kirsten
TB
,
Chaves-Kirsten
GP
,
Bernardes
S
,
Scavone
C
,
Sarkis
JE
,
Bernardi
MM
,
Lipopolysaccharide exposure induces maternal hypozincemia, and prenatal zinc treatment prevents autistic-like behaviors and disturbances in the striatal dopaminergic and mTOR systems of offspring
.
PLoS One
.
2015 Jul
;
10
(
7
):
e0134565
. .
71.
Alanazi
AS
.
The role of nutraceuticals in the management of autism
.
Saudi Pharm J
.
2013 Jul
;
21
(
3
):
233
43
. .
72.
Cannell
JJ
.
Autism, will vitamin D treat core symptoms?
Med Hypotheses
.
2013 Aug
;
81
(
2
):
195
8
. .
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.