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Food and Chemical Toxicology 49 (2011) 893897

Contents lists available at ScienceDirect

Food and Chemical Toxicology

journal homepage: www.elsevier.com/locate/foodchemtox

Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin-induced

diabetic rats
Kondeti Ramudu Shanmugam a,b, Korivi Mallikarjuna c, Nishanth Kesireddy d,
Kesireddy Sathyavelu Reddy a,
a

Division of Molecular Biology and Exercise Physiology, Department of Zoology, Sri Venkateswara University, Tirupati, AP 517 502, India
Department of Nutrition and Dietetics, Faculty of Allied and Health Sciences, University of Kebangsaan Malaysia, Jalan Raja Muda Aziz, 50300 Kuala Lumpur, Malaysia
Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei City, 11153 Taiwan, ROC
d
Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102-1982, USA
b
c

a r t i c l e

i n f o

Article history:
Received 6 July 2010
Accepted 15 December 2010
Available online 22 December 2010
Keywords:
Diabetes
Ginger
Anti-hyperglycemic
Anti-oxidant
Lipid peroxidation

a b s t r a c t
The aim of the present study was to investigate the effect of ginger on oxidative stress markers in the
mitochondrial fractions of cerebral cortex (CC), cerebellum (CB), hippocampus (HC) and hypothalamus
(HT) of diabetic rats. Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative
damage. A marked decrease in anti-oxidant marker enzymes, superoxide dismutase (SOD), catalase
(CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH) and increase
in malondialdehyde (MDA) was observed in the diabetic rats. Decreased activities of anti-oxidant
enzymes in diabetic rats were augmented on oral administration of ginger. Moreover, ginger administration depleted the MDA level, which was earlier increased in the diabetic rats. These results suggest that
ginger exhibit a neuroprotective effect by accelerating brain anti-oxidant defense mechanisms and down
regulating the MDA levels to the normal levels in the diabetic rats. Thus, ginger may be used as therapeutic agent in preventing complications in diabetic patients.
2010 Elsevier Ltd. All rights reserved.

1. Introduction
Diabetes mellitus is one of the most common metabolic disorders with a worldwide prevalence estimated to be between 1%
and 5% (Meral et al., 2004). In India, over 20 million peoples are affected by diabetes and the number are expected to increase to 57
million by 2025 (Arvind et al., 2002). The World Health Organization (WHO) (1985) has declared India as the country with the largest number of diabetic subjects in the world. Diabetes is one of the
stress related disorder. Diabetes mellitus has been shown to be a
state of increased free radical formation (Feillet-Coudray et al.,
1999). The existence of oxidative stress resulting from increased
free radicals has been postulated in diabetes. Animal, humans
studies and in vitro experiments suggest the role for oxidative
stress, via an increased formation of free radicals in the pathophysiology of many complications of diabetes, such as neurological,

Abbreviations: CC, cerebral cortex; CB, cerebellum; HC, hippocampus; HT,

hypothalamus; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; GR, glutathione reductase; GSH, reduced glutathione; MDA, malondialdehyde; CNS, central nervous system; WHO, World Health Organization; ROS, reactive
oxygen species; STZ, streptozotocin.
Corresponding author. Tel.: +91 877 2249666; fax: +91 877 2261801.
E-mail address: ksreddy2008@hotmail.com (K. Sathyavelu Reddy).
0278-6915/$ - see front matter 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.fct.2010.12.013

cardiovascular, retinal and renal (Brownlee, 2001). Diabetes manifested by experimental animal models exhibit high oxidative stress
due to persistent and chronic hyperglycemia, which thereby depletes the activity of antioxidative enzymes and thus promote free
radical generation (Baynes and Thorpe, 1996).
Diabetes is metabolic disorder that is known to produce
changes in various organs of the body like heart, liver kidney
and brain. Diabetes affects the central nervous system (CNS)
and produce disturbances such as neurobehavioral changes, autonomic dysfunctions, altered neuroendocrine functions and neurotransmitter alterations and thus leading to end organ damage
(Nishikawa et al., 2000; Brands et al., 2004). The CNS is highly
susceptible to oxidative stress. Most of the reactive oxygen species (ROS)-dependent central nervous disorders have been observed to be actually triggered by the presence of free radicals.
Anti-oxidant therapy has proved to be remarkably benecial to
combat ROS-induced injury in the CNS.
Plants have been the major source of drug for the treatment of
diabetes in Indian system of medicine and other ancient systems in
the world. Ginger (Zingiber ofcinale) is widely consumed as spice
for the avoring of foods. Ginger is reported to have several benecial pharmacological effects (hypoglycemic, insulinotropic, and
hypolipidemic) on health in humans (Huang et al., 2004) and in
experimental animals (Akhani et al., 2004; Kondeti et al., 2011).

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K.R. Shanmugam et al. / Food and Chemical Toxicology 49 (2011) 893897

It has been reported that ginger or its extracts posses some pharmacological activities including antiemesis (Sharma and Gupta,
1998), analgesic effect (Young et al., 2005), anti-tumor (Katiyar
et al., 1996) and anti-oxidant (Shanmugam et al., 2010). Anti-oxidants in ginger include gingerols, shogaols and some phenolic ketone derivatives. The anti-inammatory and anti-oxidant
properties in ginger help relieve various inammatory disorders
like gout, osteoarthritis, and rheumatoid arthritis. It provides substantial relief in pain caused by inammation and help decrease
swelling and morning stiffness (Habib et al., 2008). Ginger has been
reported to contain many phytochemicals like phenols, avanoids,
terpenoids and other phytochemicals which are responsible for
their pharmacological activities. Its dried extract contains monoterpenes and sesquiterpenes.
However, the effects of ginger have not been studied for its antioxidant actions on diabetic brain parts. Thus, the present study
aims to investigate the neuroprotective effect of ginger on oxidative damage in the brain parts of streptozotocin-induced diabetic
rats.

Group 4. Diabetic + ginger treatment (D + Gt): diabetic rats received ginger ethanolic extract (200 mg/kg) for a period of 30 days.
Group 5. Diabetic + glibenclamide treatment (D + Gli): diabetic rats treated
with glibenclamide (600 lg/kg body weight orally).
After completion of 30 days treatment the animals were sacriced by cervical
dislocation and the brain tissues were excised at 4 C. Different regions of brain
cerebral cortex (CC), cerebellum (CB), hippocampus (HP) and hypothalamus (HT)
were isolated according to specic anatomical marks according to Glowinski and
Iversen (1966). The tissues were washed with ice-cold saline, immersed in liquid
nitrogen and immediately stored at 80 C for further biochemical analysis.
2.5. Isolation of mitochondria

2. Materials and methods

The isolation of mitochondria was done by using the methods of Kaushal et al.
(1999). The brain regions were quickly removed and placed in beakers containing
chilled ( 4 C) isolation media. The isolation medium for brain contained 0.25 M
sucrose, 10 mM TrisHCl buffer, pH 7.4, 1 mM EDTA and 250 lg BSA/ml. The tissues
were minced if necessary and washed repeatedly with the isolation medium to remove adhering blood and 10% (w/v) homogenates were prepared using homogenizer. The nuclei and cell debris were sedimented by centrifugation at 650g for
10 min and discarded. The supernatant was subjected to a further centrifugation
at 7500g for 10 min. The resulting mitochondrial pellet was washed by suspending
gently in the isolation medium and by resedimenting at 7500g for 10 min. Finally,
the mitochondria were suspended in the isolation medium.

2.1. Animals

2.6. Analytical procedures

Wistar strain male albino rats aged 6 months, weighing 180 20 g were obtained from Indian Institute of Science, Bangalore. The rats were housed in clean
polypropylene cages having six rats per cage and maintained under temperature
controlled room (27 2 C) with a photoperiod of 12 h light and 12 h dark cycle.
The rats were given standard pellets diet (Lipton rat feed, Ltd., Pune) and water
ad libitum throughout the experimental period.
The experiments were carried out in accordance with guidelines and protocol
approved by the Institutional Animal Ethics Committee (Regd. No. 438/01/a/CPCSEA/dt.17.07.2001) in its resolution number 9/IAEC/SVU/2001/dt. 4.03.2002.

SOD activity was assayed in the mitochondrial fraction by the method of Misra
and Fridovich (1972) at 480 nm for 4 min on a Hitachi U-2000 spectrophotometer.
Activity was expressed as the amount of enzyme that inhibits the oxidation of epinephrine by 50%, which is equal to 1 U per milligram of protein. CAT activity was
determined at room temperature by using the modied version of Aebi (1984)
and absorbance of the sample was measured at 240 nm for 1 min in a UV-spectrophotometer. Activity of GPx was determined by the method of Flohe and Gunzler
(1984) in the presence of NADPH and absorbance was measured at 340 nm using
cumene hydrogen peroxide. GR enzyme activity was determined according to the
method of Carlberg and Mannervik (1985).
The concentration of reduced GSH was measured as described by Akerboom and
Sies (1981). The extent of lipid peroxidation was estimated as the concentration of
thiobarbituric acid reactive product MDA by using the method of Ohkawa et al.
(1979). All the enzyme activities were expressed per mg protein and the tissue protein was estimated according to the method of Lowry et al. (1951) using bovine serum albumin (BSA) as a standard.
The blood glucose levels were measured by using Accucheck glucometer (Roche
Germany).

2.2. Chemicals
STZ was obtained from Sigma chemicals (USA). All the other chemicals used
were of analytical grade.
2.2.1. Induction of diabetes
The animals were fasted overnight and diabetes was induced by a single intraperitoneal injection of a freshly prepared solution of streptozotocin (STZ) (50 mg/kg
body weight) in 0.1 M cold citrate buffer (pH 4.5). The animals were considered as
diabetic, if their blood glucose values were above 250 mg/dl on the third day after
STZ injection. Ginger treatment was given to the diabetic rats for 30 days.
2.3. Ginger ethanolic extract preparation
The fresh rhizomes of ginger was locally purchased in Tirupati (AP, India) during
the period of August, identied and authenticated by botanist, Dr. Madhva Chetty in
the department of Botany, S.V. University. A voucher specimen bearing the number
1556 is deposited in the department. Two kilograms of air-dried rhizomes of the
herb was milled into ne powder mechanically and extracted in cold percolation
with 95% ethanol for 24 h. The extract was recovered and 95% ethanol was further
added to the ginger powder and the extraction was continued. This process was repeated three times. The three extracts were pooled together, combined, ltered and
the ltrate was concentrated to dryness under reduced pressure in a rotary evaporator. The resulting ethanolic extract was air-dried, nally give 80 g of dark brown,
gelatinous extract of ginger dried rhizomes. Without any further purication, the
crude ethanolic extract was used for the experiments. Dose equivalent to 200 mg
of the crude extract per kg body weight, was calculated and suspended in 2%, v/v
Tween 80 solution for the experiment (Bhandari et al., 2005).
2.4. Grouping of animals
The rats were divided into ve groups, six rats in each group and treated as
follows:
Group 1. Normal control (NC): this group of rats received vehicle solution (2% of
Tween 80).
Group 2. Ginger treatment (Gt): six rats received ethanolic extract of ginger
with a dose of 200 mg/kg body weight via oral gavage for 30 days.
Group 3. Diabetic control (STZ 50 mg/kg body weight) (DC): streptozotocin is
given intraperitonially for the induction of diabetes to this group.

2.7. Statistical analysis

Analysis of variance (ANOVA) and Duncans multiple comparison tests among
data were carried out using the SPSS (Version 13.5; SPSS Inc., Chicago, IL, USA) and
M.S. Ofce, excel software for the signicance of the main effects (factors), and treatments along with their interactions. Statistical signicance was set at p < 0.05.

3. Results
3.1. Blood glucose and body weight changes
The STZ-induced diabetic rats had shown signicant increase of
blood glucose levels in comparison to normal control rats, which
further increased during the experimental period. Oral administration of ginger signicantly decreases the blood glucose levels in
comparison to diabetic group. However, glibenclamide treatment
also decreased the blood glucose levels in a signicant manner
when compared to diabetic group. The body weight of diabetic rats
was also lower than the control group. However, ginger and glibenclamide treatments signicantly improved the body weight and
brought down towards near normal level (Table 1).
3.2. Anti-oxidant prole and lipid peroxidation
Fig. 1 represents the activity of oxidative stress marker enzymes
in the different experimental groups. There was signicant depletion in the SOD, CAT and GPx activities in the cerebral cortex,

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K.R. Shanmugam et al. / Food and Chemical Toxicology 49 (2011) 893897

Table 1
Blood glucose levels and body weight changes in STZ-induced rats followed by ginger
and glibenclamide treatment.
Groups

Group
Group
Group
Group
Group

I (NC)
II (Gt)
III (DC)
IV (D + Gt)
V (D + Gli)

Blood glucose (mg/dl)

Body weight (g)

0th Day

30th Day

0th Day

30th Day

81 1.41
83 1.47
253 3.53
259 4.09w
260 1.79w

94 2.8
88 1.87
269 15.6
138 5.84
91 3.71w

195 9.66
200 7.07
187 2.73
185 6.32
190 3.12

215 14.28
90 8.01
150 6.83
190 4.08w
205 2.07w

All the values are mean SD of six individual observations.

Values are signicant compared to normal control (p < 0.001) and diabetic control
(wp < 0.01).

hypothalamus of all the experimental groups. The activity of GR

and reduced GSH level was decreased in all the regions of brain
in diabetic group compared normal control, but it increased to
the level of normal controls in the ginger treated diabetic group
(p < 0.01).
The production of thiobarbituric acid reactive substances
(TBARS), MDA as an index of lipid peroxidation is also presented
in Fig. 2. The results demonstrate that the lipid peroxidation is increased in cerebral cortex, cerebellum, hippocampus and hypothalamus of diabetic brain as compared to normal control group
(p < 0.001). However, ginger treatment decreased the lipid peroxidation diabetic group (p < 0.01).
4. Discussion

D+Gt
D+Gli

*
CB

Gt
DC

CC

NC

HC

HT

Treatment

CAT
2
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0

NC

CB

Gt
DC
D+Gt

CC

HC

D+Gli

HT

Treatment

GPx
2.5

1.5
1

CB

HC

Gt
DC
D+Gli

0.5
CC

NC

D+Gt

*
*

GR
7

6
5

3
2

NC

CC

CB

HC

DC
D+Gt
D+Gli

1
0

Gt

HT

Treatment

micromoles of NADPH oxidized /

mg protein/minute

SOD

HT

Treatment

Fig. 1. Status of superoxide dismutase (SOD), catalase (CAT) and glutathione

peroxidase (GPx) activities in cerebral cortex (CC), cerebellum (CB), hippocampus
(HC) and hypothalamus (HT) of rat brain. The values are signicant compared to the
following: control (p < 0.001), diabetic (wp < 0.01) (Dunnetts multiple comparison
test).

micro moles of thiourea/mg of

protein/hour

40
35
30
25
20
15
10
5
0

Diabetes is possibly the worlds fastest growing metabolic

disease, and as knowledge of the heterogeneity of this disorder
increases, so does the need for more appropriate therapies
(Bandyopadhyay, 2004). Currently, available drug regimens for
management of diabetes have certain drawbacks such as vascular
complications, hepatotoxicity, cardiotoxicity and neuronal toxicity.

micro moles of malondialdehyde

/gram wet weight of the tissue

micro moles of NADPH oxidized/mg

protein/minute

micro moles of hydrogen peroxide

degraded/mg protein/minute

Superoxide anion reduced/mg

protein/minute

cerebellum, hippocampus and hypothalamus of the diabetic rat

brain (p < 0.001). However ginger treatment signicantly reverses
the SOD, CAT and GPx back to normal levels (p < 0.01).
Fig. 2 depicts the activity of GR and the levels of reduced
GSH, MDA in the cerebral cortex, cerebellum, hippocampus and

GSH
8
7
6
5
4
3
2
1
0

NC

CC

CB

DC
D+Gt

Gt

D+Gli

HC

HT

Treatment

MDA

250
200

150
100
50
0

CC

NC

Gt
DC
D+Gt
D+Gli

CB

HC

HT

Treatment

Fig. 2. Alterations in glutathione reductase (GR) activity and reduced glutathione

(GSH), MDA levels on STZ induction followed by ginger and glibenclamide. The
values are signicant compared to the following: control (p < 0.001), diabetic
(wp < 0.01) (Dunnetts multiple comparison test).

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K.R. Shanmugam et al. / Food and Chemical Toxicology 49 (2011) 893897

Management of diabetes with the agents devoid of any side effects

is still a challenge to the medical system. This has led to an increase
in the demand for natural products with anti-hyperglycemic activity and fewer side effects. Traditional plant medicines are used
throughout the world for a range of diabetic conditions. The study
of such medicines might offer a natural key to unlock a diabetologists pharmacy for the future (Anjali and Manoj, 1995).
Diabetes is associated with a higher oxidative stress. ROS induced damage to the insulin-producing pancreatic beta-cells induces diabetes. Anti-oxidant therapy involving the use of herbs
and spices has been shown to protect the tissues against such damage. It has been shown that under physiological conditions glucose
may undergo auto-oxidation and contribute to ROS formation (Sen,
1995). Diabetes induced oxidative damage is responsible for the
changes occurring in the activities of anti-oxidant enzymes leading
to impaired neuronal activity.
Streptozotocin injection resulted in diabetes mellitus, which
may be due to destruction of beta cells of Islets of Langerhans as
proposed by others (Kavalali et al., 2002). Diabetes arises from irreversible destruction of pancreatic beta cells, causing degranulation
and reduction of insulin secretion (Zhang and Tan, 2000). STZ-induced diabetes is characterized by a severe loss in body weight
(Chen and Ianuzzo, 1982) and may exhibit most of the diabetic
complications such as, myocardial, cardiovascular, nervous,
kidney and urinary bladder dysfunction through oxidative stress
(Rajasekaran et al., 2005). After 30 days supplementation of ethanolic extract of ginger to diabetic rats, resulted signicant diminution of fasting blood glucose level in respect to diabetic control
rats, but no signicant alteration of fasting blood glucose level to
the control, which further strengthen the antidiabetogenic action
of ginger extract. Many investigators reported that phenols, polyphenolic compounds and avonoids of ginger are responsible for
hypoglycemic and other pharmacological activities (Jiang et al.,
2006). The decrease in body weight in diabetic rats shows that
the loss or degradation of structural proteins is due to diabetes,
and structural proteins are known to contribute to the body weight
(Rajkumar and Govindarajulu, 1991). The present study demonstrated that ginger treatment for 30 days shows anti-hyperglycemic effect in diabetic rats. When diabetic rats were treated with
ginger, the weight loss was recovered. Our results are supporting
its use as folklore medicine for the treatment of diabetes. Ginger
treatment was comparable with glibenclamide treatment a
standard hypoglycemic drug (Table 1).
Oxidative stress is the imbalance between production and removal of reactive oxygen species. Increased oxidative stress, which
contributes substantially to the pathogenesis of diabetic complications, is the consequences of either enhanced ROS production or
attenuated ROS scavenging capacity. Several reports have shown
the alterations in the anti-oxidant enzymes during diabetic condition (Preet et al., 2005). The antioxidative defense system enzymes
like SOD and CAT showed lower activities in cerebral cortex, cerebellum, hippocampus and hypothalamus during diabetes and the
results agree well with the earlier published data (El-Missiry
et al., 2004; Siddiqui et al., 2005). The decreased activities of SOD
and CAT may be a response to increased production of hydrogen
peroxide and superoxide by the auto-oxidation of excess glucose
and non-enzymatic glycation of proteins (Argano et al., 1997).
Pigeolet et al. (1990) have reported the partial inactivation of these
enzyme activities by hydroxyl radicals and hydrogen peroxide.
The decreased activity of SOD and CAT could also be due to their
decreased protein expression levels in the diabetic condition as reported recently by Sindhu et al. (2004). Administration of ginger to
diabetic rats increased the activities of SOD and CAT and may help
to control free radical, as ginger offered protection to cells against
oxidative stress by scavenging free radicals (Guo et al., 1997)

generated during diabetic condition (Mahesh et al., 2005). The increased activities of anti-oxidant enzymes may act as an added
compensation mechanism to maintain the cell integrity and protection against free radical damage. This may be due to the presence of many anti-oxidant compounds like gingerols, shogaols,
phenolic ketone derivatives, volatile oils, and avonoids in ginger.
These anti-oxidant compounds may modulate the anti-oxidant enzymes in diabetic rats (Manju and Nalini, 2005; Young et al., 2005)
(Fig. 1).
A prominent imbalance between reactive oxygen species production and endogenous anti-oxidant defense mechanism has
been conrmed by reduced activity of GPx and GR in diabetic rats
in the present study (Rastogi et al., 2008). Decreased GPx and GR
activities indicates production of lipid peroxides and elevated
H2O2 production. Treatment with ginger signicantly potentiates
above enzyme activities and the results are in agreement with
the previous reports (Levy et al., 1999). Thus, our ndings suggest
that ginger exhibits potent anti-oxidant activity by scavenging free
radicals and restoring the imbalance between oxidants/anti-oxidant homeostasis developed during diabetic condition (Figs. 1
and 2).
Reduced GSH content was decreased in diabetic rats. Depletion
of GSH levels enhances cellular damage caused by oxidative stress.
Signicant depletion of GSH (p < 0.001) in diabetic rats suggests its
increased utilization against reactive oxygen species (Rastogi et al.,
2008). However with ginger treatment in diabetic rats, the GSH
level is reversed back to normal levels, this shows that gingers
anti-oxidant property. Reports are available on anti-oxidant effect
of ginger by decreasing lipid peroxidation, increasing GSH level
and maintaining normal levels of anti-oxidant enzymes (Ahmed
et al., 2000; Ajith et al., 2007). A number of investigators have
reported that phenols, tannins and terpenoids of ginger possess
anti-oxidant activity in various experimental models (Young
et al., 2005) (Fig. 2).
The increased lipid peroxidation during diabetes, as found in
the present study may be due to the inefcient anti-oxidant system
prevalent in diabetes. (Siddiqui et al., 2005; Rastogi et al., 2008).
The elevated lipid peroxidation is responsible for the formation
of lipid hydroperoxides in membrane and would result in damage
of the membrane structure and inactivation of membrane bound
enzymes. The accumulation of lipid peroxides adds hydrophilic
moieties into the hydrophobic phase and thereby brings about
changes in the membrane permeability and cell functions (Pascoe
and Redd, 1989). Elevated oxidative stress due to this imbalance
leads to neuronal injury through oxidized proteins and augmented
levels of lipid peroxidation, as indicated by increased MDA content
on STZ induction in the present study. Ginger and glibenclamide
treatments signicantly reduces this enhanced lipid peroxidation
and the marked activity is consistent with the previously published
reports of ginger (Srinivasan and Sambaiah, 1991; Afshari et al.,
2007). The anti-oxidant compounds and other pharmacological
compounds of ginger may inhibit the production of free radicals,
and reduced the products of lipid peroxidation (Fig. 2).
In conclusion, the data from our study suggest that ginger exhibit neuroprotective effect against oxidative damage in the diabetic
rats. Since, ginger has prevented the brain damage from STZ induced oxidative stress. It is now apparent that the future approach
to treat diabetes and its associated complications must consider
either the use of ginger or combinations of herbal plants having
multi-pharmacological activities. Ginger may be ideal because they
contain a variety of pharmacological compounds with different
known pharmacological actions. However, further research is
needed, for the better understanding of the mechanism of action
of ginger by which it modulates anti-oxidant enzymes in diabetic
condition.

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K.R. Shanmugam et al. / Food and Chemical Toxicology 49 (2011) 893897

Conict of Interest
The authors declare that there are no conicts of interest.

References
Aebi, H., 1984. Catalase in vitro. Methods Enzymol. 105, 125126.
Afshari, A.T., Shirpoor, A., Farshid, A.A., Saadatian, R., Rasmi, Y., Saboory, E.,
Ilkhanizadeh, B., Allameh, A., 2007. The effect of ginger on diabetic
nephropathy, plasma antioxidant capacity and lipid peroxidation in rats. Food
Chem. 101, 148153.
Ahmed, R.S., Seth, V., Banerjee, B.D., 2000. Inuence of dietary ginger (Zingiber
ofcinale Rosc.) on antioxidant defense system in rat: comparison with ascorbic
acid. Ind. J. Exp. Biol. 38, 604606.
Ajith, T., Nivitha, V., Usha, S., 2007. Zingiber ofcinale Roscoe alone and in
combination with a tocopherol protect the kidney against cisplatin-induced
acute renal failure. Food Chem. Toxicol. 45, 921927.
Akerboom, T.P., Sies, H., 1981. Assay of glutathione, glutathione disulde and
glutathione mixed disuldes in biological samples. Methods Enzymol. 77, 373
382.
Akhani, S.P., Vishwakarma, S.L., Golyal, R.K., 2004. Anti-diabetic activity of Zingiber
ofcinale in streptozotocin-induced type I diabetic rats. J. Pharm. Pharmacol. 56,
101105.
Anjali, P., Manoj, K.M., 1995. Some comments on diabetes and herbal therapy. Anc.
Sci. Life 15, 2729.
Argano,
M.,
Brignardello,
E.,
Tamagno,
O.,
Boccuzzi,
G.,
1997.
Dehydroeppiandrosterone administration prevents the oxidative damage
induced by acute hyperglycemia in rats. J. Endocrinol. 155, 233240.
Arvind, K., Pradeepa, R., Deepa, R., Mohan, V., 2002. Diabetes and coronary artery
disease. Ind. J. Med. Res. 116, 163176.
Bandyopadhyay, P., 2004. Advances in the understanding of diabetes mellitus. Drug
News Perspect. 17, 477487.
Baynes, J.W., Thorpe, S.R., 1996. The role of oxidative stress in diabetic
complications. Curr. Opin. Endocrinol. 3, 277284.
Bhandari, U., Kanojia, R., Pillai, K.K., 2005. Effect of ethanolic extract of Zingiber
ofcinale on dyslipidaemia in diabetic rats. J. Ethnopharmacol. 97, 227230.
Brands, A.M.A., Kessels, R.P.C., De Haan, E.H.F., Kappelle, L.J., Biessels, G.J., 2004.
Cerebral dysfunction in type I diabetes: effects of insulin, vascular risk factors
and blood glucose levels. Eur. J. Pharmacol. 490, 159168.
Brownlee, M., 2001. Biochemistry and molecular cell biology of diabetic
complications. Nature 414, 813820.
Carlberg, I., Mannervik, B., 1985. Glutathione reductase. Methods Enzymol. 113,
484490.
Chen, V., Ianuzzo, C.D., 1982. Dosage effect of streptozotocin on rat tissue enzyme
activities and glycogen concentration. Can. J. Physiol. Pharmacol. 60, 1251
1256.
El-Missiry, M.A., Othman, A.I., Amer, M.A., 2004. L-arginine ameliorates oxidative
stress in alloxan-induced experimental diabetes mellitus. J. Appl. Toxicol. 24
(2), 9397.
Feillet-Coudray, C., Rock, E., Coudray, C., Grzelkowska, K., Azais-Braesco, V.,
Dardevet, D., 1999. Lipid peroxidation and antioxidant status in experimental
diabetes. Clin. Chim. Acta 284, 3143.
Flohe, L., Gunzler, W.A., 1984. Assays of glutathione peroxidase. Methods Enzymol.
105, 114121.
Glowinski, J., Iversen, L.L., 1966. Regional studies of catecholamines in the rat brain.
J. Neurochem. 13, 665669.
Guo, P., Xu, J., Xu, S., Wang, K., 1997. Inhibition of hydrogen peroxide production in
chondrocytes induced by fulvic acid by ginger volatile oil. Chung Kuo Chung Yao
Tsa Chi 22, 559561.
Habib, S.H., Makpol, S., Abdul Hamid, N.A., Das, S., Ngah, W.Z., Yusof, Y.A., 2008.
Ginger extract (Zingiber ofcinale) has anti-cancer and anti-inammatory effects
on ethionine-induced hepatoma rats. Clinics 63 (6), 807813.
Huang, C.N., Horng, J.S., Yin, M.C., 2004. Antioxidative and antiglycative effects of six
organosulfur compounds in low-density lipoprotein and plasma. J. Agric. Food
Chem. 52 (11), 36743678.
Jiang, H., Xie, Z., Koo, H.J., McLaughlin, S.P., Timmermann, B.N., Gang, D.R., 2006.
Metabolic proling and phylogenetic analysis of medicinal Zingiber species:
tools for authentication of ginger (Zingiber ofcinale Rosc.). Phytochemistry 67,
16731685.

897

Katiyar, S.K., Agarwal, R., Mukhtar, H., 1996. Inhibition of tumor promotion in
SENCAR mouse skin by ethanol extract of Zingiber ofcinale rhizome. Cancer Res.
56, 10231030.
Kaushal, R., Dave, K.R., Katyare, S.S., 1999. Paracetamol hepatotoxicity and
microsomal function. Environ. Toxicol. Pharmacol. 1, 6774.
Kavalali, G., Tuncel, H., Gksel, S., Hatemi, H.H., 2002. Hypoglycemic activity of
Urtica pilulifera in streptozotocin-diabetic rats. J. Ethnopharmacol. 84, 241245.
Kondeti, R.S., Korivi, M., Kesireddy, N., Kuo, Chia Hua, Kesireddy, S.R., 2011.
Protective effect of dietary ginger on antioxidant enzymes and oxidative
damage in experimental diabetic rat tissues. Food Chem. 124 (4), 14361442.
Levy, Y., Zaltzberg, H., Ben-Amotz, A., Kanter, Y., Aviram, M., 1999. b-Carotene
affects antioxidant status in non-insulin dependent diabetes mellitus.
Pathophysiology 6, 157161.
Mahesh, T., Balasubashini, M., Menon, V., 2005. Effect of photo-irradiated curcumin
treatment against oxidative stress in STZ-induced diabetic rats. J. Med. Food 8,
251255.
Manju, V., Nalini, N., 2005. Chemopreventive efcacy of ginger, a naturally
occurring anticarcinogen during the inition, post-inition stages of 1,2
dimethylhydrazine-induced colon cancer. Clin. Chim. Acta 358, 6067.
Meral, L., Donmez, N., Baydas, B., Belge, E., Kanter, M., 2004. Effect of Nigella sativa L.
on heart rate and some haematological values of alloxan-induced diabetic
rabbits. Scand. J. Lab. Anim. Sci. 31 (1), 4953.
Misra, H.P., Fridovich, I., 1972. The role of superoxide anion in the autooxidation of
epinephrine and a simple assay for superoxide dismutase. J. Biol. Chem. 247,
31703175.
Nishikawa, T., Edelstein, D., Du, X.L., Yamagishi, S., Matsumura, T., Kaneda, Y., Yorek,
M.A., Beebe, D., Oates, P.J., Hammes, H.P., Giardino, I., Brownlee, M., 2000.
Normalizing mitochondrial superoxide production blocks three pathways of
hyperglycaemic damage. Nature 404 (6779), 787790.
Ohkawa, H., Ohishi, N., Yagi, K., 1979. Assay for lipid peroxides in animal tissues by
thiobarbituric acid reaction. Anal. Biochem. 95, 351358.
Pascoe, G.A., Redd, D.J., 1989. Cell calcium, vitamin E and the thiol redox system in
cystotoxicity. Free Radical Biol. Med. 6, 209224.
Pigeolet, E., Corbisier, P., Houbion, A., Lambert, D., Michiels, C., Raes, M., Zachary, M.,
Remacle, J., 1990. Glutathione peroxidase, superoxide dismutase and catalase
inactivation by peroxide and oxygen derived free radicals. Mech. Aging Dev. 51,
283297.
Preet, A., Gupta, B.L., Yadava, P.K., Baquer, N.Z., 2005. Efcacy of lower doses of
vanadium in restoring altered glucose metabolism and antioxidant status in
diabetic rat lenses. J. Biosci. 30, 221230.
Rajasekaran, S., Sivagnanam, K., Subramanian, S., 2005. Antioxidant effect of
Aloe vera gel extract in streptozotocin diabetes in rats. Pharmacol. Rep. 57,
9096.
Rajkumar, L., Govindarajulu, P., 1991. Increased degradation of dermal collagen in
diabetic rats. Ind. J. Exp. Biol. 29, 10811083.
Rastogi, M., Ojha, R.P., Rajamanickam, G.V., Agrawal, A., Aggarwal, A., Dubey, G.P.,
2008. Curcuminoids modulates oxidative damage and mitochondrial
dysfunction in diabetic rat brain. Free Radical Res. 42 (1112), 9991005.
Sen, C.S., 1995. Oxygen toxicity and antioxidants: state of the rat. Ind. J. Physiol.
Pharmacol. 39, 177196.
Shanmugam, K.R., Ramakrishna, C.H., Mallikarjuna, K., Sathyavelu Reddy, K., 2010.
Protective effect of ginger in alcohol-induced renal damage and antioxidant
enzymes in male albino rats. Ind. J. Exp. Biol. 4, 143149.
Sharma, S.S., Gupta, Y.K., 1998. Effect of ginger (Zingiber ofcinale) against cisplatin
induced delay in gastric emptying in rats. J. Ethnopharmacol. 62, 4955.
Siddiqui, M.R., Taha, A., Moorthy, K., Hussain, E., Basir, S.F., Baquer, N.Z., 2005.
Amelioration of altered antioxidants status and membrane linked functions by
vanadium and Trigonella in alloxan diabetic rat brains. J. Biosci. 30 (4), 483490.
Sindhu, R.K., Koo, J.R., Roberts, C.K., Vaziri, N.D., 2004. Dysregulation of hepatic
superoxide dismutase, catalase and glutathione peroxidase in diabetes response
to insulin and antioxidant therapies. Clin. Exptl. Hypertens. 26, 4353.
Srinivasan, K., Sambaiah, K., 1991. The effect of spices on cholesterol 7 alphahydroxylase activity and on serum and hepatic cholesterol levels in the rat. Int.
J. Vitam. Nutr. Res. 61, 363369.
World Health Organization, 1985. Diabetes mellitus: report of a WHO Study Group.
WHO Technical Report Series, p. 727.
Young, H.Y., Luo, Y.L., Cheng, H.Y., Hsieh, W.C., Liao, J.C., Peng, W.H., 2005. Analgesic
and anti-inammatory activities of [6]-gingerol. J. Ethnopharmacol. 96 (12),
207210.
Zhang, C.Y., Tan, B.K., 2000. Antihyperglycaemic and anti-oxidant properties of
Andrographis paniculata in normal and diabetic rats. Clin. Exp. Pharmacol. 27,
358363.