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Advanced Pharmaceutical Bulletin, 2013, 3(2), 273-276
doi: http://dx.doi.org/10.5681/apb.2013.044
http://apb.tbzmed.ac.ir/
*Corresponding author: Alireza Ostadrahimi, Tabriz University of Medical Sciences, Tabriz, Iran. Tel: +98(411)335-7310.
Email: ostadrahimi@tbzmed.ac.ir
Copyright © 2013 by Tabriz University of Medical Sciences
Anti-Inflammatory Effects of Zingiber Officinale in Type 2 Diabetic
Patients
Sepide Mahluji1, Alireza Ostadrahimi2*, Majid Mobasseri3, Vahide Ebrahimzade Attari1, Laleh Payahoo1
1 Student Research Committee, Tabriz University of Medical Science, Tabriz, Iran.
2 Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Endocrinology and Metabolism Section, Department of Medicine, Imam Reza Hospital, Tabriz, Iran.
Introduction
Ginger (Zingiber officinale) has been cultivated for
thousands of years as a flavoring agent and cooking
spice. In addition, it has been used in traditional
systems of medicine for a wide range of ailments
including pain, muscholar aches, fever, sore throats,
indigestion and vomiting.1 On the other hand, recent
studies showed some benefits of ginger to treat
musculoskeletal disorder,2 nausea and vomiting,3
inflammation or inflammatory states4 such as
osteoarthritis,4,5 migraine,6 cancer7, hyperlipidemia and
hyperglycemia.1,8
According to the results of some in vitro studies,
rhizome of ginger and its main components, gingerols
and shogaols, can inhibit synthesis of several pro-
inflammatory cytokines including IL-1, TNF-α and IL-
8 along with inhibiting prostaglandin (PG) and
leukotriene (LT) synthesis enzymes.9
More recently, investigations showed that ginger has an
effect on several genes encoding cytokines,
chemokines and the inducible enzyme cyclo-
oxygenase-2 (COX-2).10 Besides, it has been shown
that the components of ginger are more effective than
conventional non-steroidal anti-inflammatory drugs
(NSAIDs) with fewer side effects.11
Therefore, there is a hypothesis that ginger may have
useful effects on diabetes with a chronic low-grade
inflammation. Chronic hyperglycemia increases
circulating levels of inflammatory biomarkers such as
IL-6 (IL6), tumor necrosis factor-α (TNF-α) and C-
reactive protein (CRP). TNF-α and IL-6, as the major
cytokines, initiate inflammatory responses and cause
the production of CRP as an acute-phase reactant.12
Moreover, lots of evidences showed that low-grade
inflammation, a common feature in type 2 diabetes
mellitus (DM2), play a major role in pathogenesis of its
secondary complications such as atherothrombosis.13
Although, ginger has hypoglycemic and anti-
inflammatory effects, just a few studies have reported
its anti-inflammatory activity during diabetes.14 An
animal study on the anti-inflammatory effects of ginger
extract on diabetic rats reported the reduced level of
TNF-α consequent to ginger extract treatment.15
Therefore, the present study was planned to evaluate
the effect of ginger powder supplementation on pro-
inflammatory cytokines (IL-6, TNF-α) and hs-CRP in
DM2 patients.
A R T I C L E I N F O
A B S T R A C T
Article Type:
Research Article
Article History:
Received: 29 November 2012
Revised: 17 January 2013
Accepted: 17 January 2013
ePublished: 20 August 2013
Keywords:
Ginger
Inflammation
TNF-α
Diabetes
Purpose: Low-grade inflammation, a common feature in type 2 diabetes (DM2), causes
some chronic complications in these patients. The present study was aimed to evaluate
the effects of ginger (Zingiber officinale) on pro-inflammatory cytokines (IL-6 and
TNF-α) and the acute phase protein hs-CRP in DM2 patients as a randomized double-
blind placebo controlled trial. Methods: A total of 64 DM2 patients randomly were
assigned to ginger or placebo groups and received 2 tablets/day of each for 2 months.
The concentrations of IL-6, TNF-α and hs-CRP in blood samples were analyzed before
and after the intervention. Results: Ginger supplementation significantly reduced the
levels of TNF-α (P = 0.006), IL-6 (P = 0.02) and hs-CRP (P = 0.012) in ginger group in
comparison to baseline. Moreover, the analysis of covariance showed that the group
received ginger supplementation significantly lowered TNF- α (15.3 ± 4.6 vs. 19.6 ±
5.2; P = 0.005) and hs-CRP (2.42 ± 1.7 vs. 2.56 ± 2.18; P = .016) concentrations in
comparison to control group. While there were no significant changes in IL-6 (7.9 ± 2.1
vs. 7.8 ± 2.9; P > .05). Conclusion: In conclusion, ginger supplementation in oral
administration reduced inflammation in type 2 diabetic patients. So it may be a good
remedy to diminish the risk of some chronic complications of diabetes.
274 |
Mahluji et al.
Advanced Pharmaceutical Bulletin, 2013, 3(2), 273-276
Copyright © 2013 by Tabriz University of Medical Sciences
Materials and Methods
Study Design
This study was a randomized, double blind, placebo
controlled trial performed on type 2 diabetic patients
with at least 2 years experience. Subjects were
recruited from diabetes association in Tabriz, Iran. The
study was approved by Medical Ethical Committee of
the Tabriz University of medical science under the
number of 5/4/3832. Exclusion criteria were insulin
therapy at baseline or during the study, smoking,
presence of pregnancy and breastfeeding, consumption
of ginger or other botanical supplements, any acute
illnesses and presence of some chronic diseases
including kidney, liver, cardiovascular, and
gastrointestinal diseases. 64 eligible patients with the
age group of 38-65 yrs of either sex fulfilled consent
paper prior to inclusion in the study.
Sample size was determined based on data from
previous study16 by considering α= 0.05 with power of
80%. The sample size was computed as 25 per group.
Regarding a possible loss to follow-up, a safety margin
of 30% was determined, and therefore 32 patients were
allocated in each group.
Treatment
All patients were randomly assigned to two groups of
32 subjects in each to receive either ginger or placebo
one tablet twice a day immediately after lunch and
dinner for 8 weeks. The patients were instructed to
maintain their diet and physical activity during the
intervention. All subjects were permitted to consume
their usual medications according to their physicians’
recommendation. The three-day food record was taken
from all patients at the beginning and end of
intervention to be confidant of constant dietary intake.
Tablets Preparation
Fresh rhizomes of zingiber officinale were purchased
from local market and were ground as a fine particle
after drying. The powder was delivered to a
pharmaceutical lab (Tabriz university of medical
science, Iran) to prepare tablets containing 1 gram
ginger in each. Starch was also used to make placebo.
The tablets were placed in the identical bottles by a
third person not directly involved in this study. This
person labeled the bottles with 2 cods which retained
unknown for researchers until the end of intervention.
To evaluate the compliance of patients, bottles
containing ginger (or placebo) tablets were given
monthly.
Anthropometric and Biochemical Assessments
Anthropometric parameters including height and
weight were measured at the beginning and end of the
intervention to calculate body mass index (BMI) as the
formula (Wt/Ht2). Body weight was measured without
shoes and light clothing by using a Seca scale (Seca,
Hamburg, Germany). Heights were also measured
using a statiometer (Seca) without shoes.
Blood samples (5ml) were taken in a 12-14 hrs fasting
state (water permitted) at the beginning and after two
months of intervention. The serum was obtained by
high speed centrifugation and was frozen immediately
at −70 °C until assay. The concentration of hs-CRP was
measured by spectrophotometer method using
parsazmun kit. IL-6 and TNF-α were also assayed
using ELISA kits according to the manufacturer’s
instruction.
Statistical Analysis
The data were analyzed by SPSS software (version 17;
SPSS Inc., Chicago, IL) and the results were expressed
as mean ± standard error. The normality of the
distribution of variables was determined by the
Kolmogorov-Smirnov test. The background
characteristics and baseline experimental data in the 2
groups were compared using independent sample t-tests
and chi-squared test. Analysis of covariance
(ANCOVA) was used to identify any differences
between 2 groups after intervention, adjusting for
baseline measurements and covariates including age
and hypoglycemic drugs. The changes of
anthropometric measurements and the concentration of
IL-6, TNF-α and hs-CRP were assessed by paired
sample t-tests in each group. Differences with P < 0.05
were considered to be statistically significant.17
Results
Of 64 patients initially recruited, 6 persons were
excluded during the study. In ginger group 2 persons
did not consume tablets according to plan, one person
traveled and one person needed to change his
medication during the intervention. In placebo group
also one people did not consume tablets according to
plan and one person traveled.
Participants represented good compliance with the
ginger consumption and no serious adverse side effects
or symptoms were reported except for two patients with
slight heart burn in the beginning of intervention.
Despite the differences in consumed hypoglycemic
drugs, it remained constant for all participants during
the study.
Table 1 shows baseline anthropometric parameters and
the levels of IL-6, TNF-α and hs-CRP in two groups.
There were no statistically significant differences
between the ginger and placebo groups (P > 0.05).
Table 1. Baseline characteristics of study participantsa
Item
Intervention (ginger)
placebo
Age (yr)
49.27±5.18
53.14±7.9
Sexb (M:F)
14:12
16:12
Weight (kg)
79.38±11.87
76.89±14.59
BMI (kg/m2)
29.2±4.07
29.8±5.05
TNF-α (Pg/ml)
16.7±4.4
18.9±5.3
IL-6 (Pg/ml)
8.6±2.7
7.6±3.0
Hs-CRP (Pg/ml)
3.37±2.8
2.23±2.3
a Data are presented as means ± standard error
b Frequency
| 275
Anti-Inflammatory Effects of Zingiber in Diabetic Patients
Advanced Pharmaceutical Bulletin, 2013, 3(2), 273-276
Copyright © 2013 by Tabriz University of Medical Sciences
Table 2 shows the concentrations of IL-6, TNF-α and
hs-CRP before and after intervention in both groups.
Ginger supplementation significantly reduced the levels
of TNF-α (P=0.006), IL-6 (P=0.02) and hs-CRP
(P=0.012) in ginger group in comparison to baseline.
These parameters remained unchanged in placebo
group during the study.
Table 2. Effects of ginger or placebo consumption on some parameters in diabetic patients1
Item
Intervention (ginger)
placebo
P
Before
after
before
after
TNF-α (Pg/ml)
16.7±4.4
15.3±4.6*
18.9±5.3
19.6±5.2
0.005
IL-6 (Pg/ml)
8.6±2.7
7.9±2.1*
7.6±3.0
7.8±2.9
0.11
Hs-CRP (Pg/ml)
3.37±2.8
2.42±1.7*
2.23±2.3
2.56±2.18
0.016
1 Data are presented as means ± SD
*P < 0.05 significantly different from baseline according to paired sample t
On the other hand, results of analysis of covariance
showed significant differences in TNF-α (P=0.005) and
hs-CRP (P=0.016) levels between two groups at the
end of study, that were in accordance with the type of
consumed hypoglycemic drug, age and baseline values.
While no statistically significant differences were
observed for IL-6 (P > 0.05) between 2 groups (Table 2).
Discussion
Recent studies have reported that ginger has anti-
inflammatory effects7 which can decline pain
associated with rheumatoid and osteoarthritis.8 On the
other hand, the role of inflammation on diabetes has
been reported in numerous studies.18 Cytokines are
associated with the pathogenesis of both type 1 and
type 2 diabetes through accelerating beta-cell apoptosis
and death. Besides, evidence have shows that insulin
resistance as a pro-inflammatory status may have
existed for years before the occurrence of type 2
diabetes.19 Moreover, increased CRP, IL-6 and TNF-α
are associated with nephropathy, retinopathy and
cardiovascular disease in both types of diabetes.20
The present study was performed with the aim of
assessing the effects of ginger powder on inflammation
under diabetic condition. The results showed that
ginger supplementation alleviated the inflammation by
reduced levels of TNF-α and hs-CRP without any
significant effects on IL-6 levels. In consistent with our
study Morakinyo et al.15 indicated that treatment with
aqueous and ethanol extracts of ginger in diabetic rats
significantly decreased the levels of TNF-α. Besides,
Fatehi-Hassanabad et al.14 reported the anti-
inflammatory effects of the aqueous extract of ginger in
diabetic mice.
A large body of evidence indicated that the major
pharmacological activity of ginger is due to gingerols
and shogaols. These compounds reduce prostaglandin
synthesis through suppression of cyclooxygenase- 1
and cyclooxygenase-2. It also has been reported that
ginger suppresses leukotriene biosynthesis by
inhibiting 5-lipoxygenase.21 In addition, ginger extract
was found to inhibit beta-amyloid peptide-induced
cytokine and chemokine expression in cell line of
human monocytes.10
Conclusion
In conclusion, during the present study oral ginger
supplementation ameliorated inflammation through
reduction in levels of TNF-α and hs-CRP
concentrations in blood samples of the patients with
type 2 diabetes mellitus. Regarding negligible side
effects of ginger, it may be a good remedy for diabetic
patients to diminish the risk of some secondary chronic
complications.
Acknowledgements
This study was supported by a grant from Research
Vice-Chancellor of Tabriz University of Medical
Sciences (Tabriz, Iran). The authors thank Tabriz
association of diabetes for helping in recruiting
patients.
Conflict of Interest
The authors have no conflict of interest.
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