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Ginger and its Health Claims: Molecular Aspects

a

Masood Sadiq Butt & M. Tauseef Sultan

National Institute of Food Science and Technology, University of Agriculture, Faisalabad,

Pakistan
b

Department of Food and Horticultural Sciences, Bahauddin Zakariya University, Multan,

Pakistan
Version of record first published: 11 Apr 2011.

To cite this article: Masood Sadiq Butt & M. Tauseef Sultan (2011): Ginger and its Health Claims: Molecular Aspects, Critical
Reviews in Food Science and Nutrition, 51:5, 383-393
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Critical Reviews in Food Science and Nutrition, 51:383393 (2011)

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ISSN: 1040-8398 print / 1549-7852 online
DOI: 10.1080/10408391003624848

Ginger and its Health Claims:

Molecular Aspects
MASOOD SADIQ BUTT1 and M. TAUSEEF SULTAN2
1

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National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan
Department of Food and Horticultural Sciences, Bahauddin Zakariya University, Multan, Pakistan

Recent research has rejuvenated centuries-old traditional herbs to cure various ailments by using modern tools like diet-based
therapy and other regimens. Ginger is one of the classic examples of an herb used for not only culinary preparations but also
for unique therapeutic significance owing to its antioxidant, antimicrobial, and anti-inflammatory potential. The pungent
fractions of ginger, namely gingerols, shogaols, paradols, and volatile constituents like sesquiterpenes and monoterpenes, are
mainly attributed to the health-enhancing perspectives of ginger. This review elucidates the health claims of ginger and the
molecular aspects and targets, with special reference to anticancer perspectives, immunonutrition, antioxidant potential, and
cardiovascular cure. The molecular targets involved in chemoprevention like the inhibition of NF-B activation via impairing
nuclear translocation, suppresses cIAP1 expression, increases caspase-3/7 activation, arrests cell cycle in G2 + M phases,
up-regulates Cytochrome-c, Apaf-1, activates PI3K/Akt/I kappaB kinases IKK, suppresses cell proliferation, and inducts
apoptosis and chromatin condensation. Similarly, facts are presented regarding the anti-inflammatory response of ginger
components and molecular targets including inhibition of prostaglandin and leukotriene biosynthesis and suppression of 5lipoxygenase. Furthermore, inhibition of phosphorylation of three mitogen-activated protein kinases (MAPKs), extracellular
signal-regulated kinases 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK) are also discussed. The role of ginger in
reducing the extent of cardiovascular disorders, diabetes mellitus, and digestive problems has also been described in detail.
Although, current review articles summarized the literature pertaining to ginger and its components. However, authors are
still of the view that further research should be immediately carried out for meticulousness.
Keywords

ginger, antioxidants, anticancer, immunonutrition, CVD, diabetes mellitus

INTRODUCTION
The dependence of humans on medicinal plants to cure various ailments has been documented since recorded history. Initially people relied on plants for food, which protected them
from physiological threats (Butt et al., 2009). Recently, a number of scientific investigations have led to the recognition of a
safe status for such natural products. In the domain of nutrition,
great effort has been made to explore the health-promoting potential of many culinary herbs. The knowledge generated from
such studies resulted in the development of modern concepts,
for example, functional and nutraceuticals foods, optimum nutrition, and food synergy (Sultan et al., 2009; Yang et al., 2009).
Consumer awareness was the guiding force behind the success of such healthy foods that have taken hold of the global

Address correspondence to M. Tauseef Sultan, Assistant Professor, Department of Food and Horticultural Sciences, Bahauddin Zakariya University,
Multan, Pakistan. Tel.: 0092-333-9949100. E-mail: tauseefsultan@yahoo.com

nutrition market (Siro et al., 2008). People consuming a diet

rich in functional or bioactive components are at lower risk
of chronic illnesses (Vina et al., 2006; Jenkins et al., 2008).
Functional foods that are predominant in the market include
green tea, soybean, flax, broccoli, grape juice, cabbage, tomatoes, raspberry, watermelon, psyllium, oats and barley, onion,
garlic, etc. (Butt et al., 2008; Mateos-Aparicio et al., 2008;
Wang et al., 2009). Some culinary commodities like garlic,
onion, ginger, fenugreek, etc., are being used for giving specific taste, aroma, and flavor to the meals. Such plants have a
rich phytochemistry correlated with their health-promoting potential (Barta et al., 2006; Espn et al., 2007). Ginger is one of
the most commonly consumed herbs with an array of applications in traditional medicines like Chinese medicine, Ayurveda,
and Unani-Tibb (Rong et al., 2009). It is generally considered
safe and it possesses various pharmacological activities including cardiovascular protection, antioxidant, anti-inflammatory,
glucose lowering, anti-cancer activities, etc. (Shukla and Singh,
2007; Nicoll and Henein, 2009). This review provides a decisive insight on the phytochemistry and health-promoting

383

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Table 1

M. S. BUTT AND M. T. SULTAN

Botanical classification

Kingdom:

Plantae

Subkingdom
Super-division
Class
Subclass
Order:
Family:
Genus:
Species:

Tracheobionta Vascular plants

Spermatophyta Seed plants
Monocotyledons
Zingiberidae
Zingiberales
Zingiberaceae (Ginger Family)
Zingiber
Officinale

J.S. Peterson @ USDA-NRCS PLANTS Database

potential of ginger against various ailments through a diet-based

regimen.

BOTANICAL CLASSIFICATION AND

PHYTOCHEMISTRY
Ginger (Zingiber officinale Rosc.) belongs to the family Zingiberaceae. It originated in South-East Asia and then became
widespread in many ecological zones; the botanical classification is cited in Table 1. It has been cultivated since long as
a spice and condiment to add flavor to Indian food (Park and
Pizzuto, 2002). Often the ginger rhizome is used to serve all
these purposes; however, some times fresh ginger is also used
as a cooking aid (Altman and Marcussen, 2001).
Besides its extensive use as a spice, the rhizome of ginger
has also been used in traditional oriental herbal medicine. The
health-promoting perspective of ginger is often attributed to its
rich phytochemistry (Shukla and Singh, 2007). The constituents
of ginger are numerous and vary depending on the place of origin
and form of rhizomes, e.g., fresh or dry. The ginger rhizome contains several components of interest, i.e., carbohydrates, miner-

als, phytochemicals, etc. It contains proximate components like

moisture, proteins, fats, fiber, ash, and carbohydrates. It also
contains appreciable amounts of vitamins and minerals as well
as some enzymes, for example, a potent proteolytic enzyme
called zingibain. Additionally, extractable oleoresins and waxes
are its fundamental constituents or functional ingredients. In a
research investigation, Onyenekwe and Hashimoto (1999) determined the essential oil of ginger using gas chromatography
and gas chromatography-mass spectrometry techniques. The
results showed that it carries 2.4% of essential oil mainly composed of 64.4% sesquiterpene, 6.6% carbonyl compounds, 5.6%
alcohols, and 2.4% monoterpene hydrocarbons. The identified
components are listed in Table 2.
Jolad et al. (2004) identified more than 60 compounds in
fresh ginger grouped into two broader categories, i.e., volatiles
and non-volatiles, contributing to specific pungency in different
ways. Volatiles include sesquiterpene and monoterpenoid
hydrocarbons providing the distinct aroma and taste of ginger.
On the contrary, non-volatile pungent compounds include gingerols, shogaols, paradols, and zingerone. Likewise, Gong et al.
(2004) analyzed both fresh and dried ginger using GC-MS and
observed varying results, and the number of components that
were reported was 140 and 136, respectively. Its main volatile

GINGER AND ITS HEALTH CLAIMS

Table 2

Phytochemicals density

Sr. #

Category

Components

Monoterpenoids

Sesquiterpenoids

Non-volatile pungent
components
Miscellaneous

Geraniol, curcumene b-phellandrene,

(+)-camphene, 1,8-cineole, citral,
terpineol, borneol, linalool, neral
Zerumbone, a-zingiberene,
b-sesquiphellandrene, b-bisabolene,
(E-E)-a-farnesene, arcurcumene,
zingiberol.
Gingerols, shogaols, paradols, zingerone

Zingibain

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Langner et al., 1998.

components are -zingiberene (22.29%), -sesquiphellandrene

(8.58%), -farnesene (3.93%), -bisabolene (3.87%), curcumene (2.63%), with [6]-gingerol (9.38%) and [6]-shogaol
(7.59%) being the promising pungent compounds. Moreover,
zingerones (9.24%) are also present in a significant amount as
they are produced during thermal degradation of gingerols or
shogaols (Zhan et al., 2008).
Gingerols are of prime importance. They are a homologous series of phenols differing in their unbranched alkyl
chains length and mainly attributed for ginger-specific pungency (Govindarajan, 1982). The quantity of [6]-gingerol in the
fresh ginger rhizome was 104965 mug/g (Nigam et al., 2009).
They are hydrated compounds that further convert to shogaols
and conversion is dependent on temperature and the pH dependence. Wohlmuth et al. (2005) and Bhattarai et al. (2001) have
already described this phenomenon. Hydrogenation of shogaols
further leads to the formation of paradol and allied derivatives
and these are implicated for the pharmacological properties of
ginger (Jiang et al., 2006).
Owing to the aforementioned phytochemistry, ginger has
been widely used in Chinese, Ayurvedic, and Unani-Tibb
medicines. Ginger has enormous health-promoting potential as
is evident when using it for treating a number of ailments including degenerative disorders (arthritis and rheumatism), digestive
health (indigestion, constipation and ulcer), cardiovascular disorders (atherosclerosis and hypertension), diabetes mellitus, and
cancer. It also has anti-inflammatory properties, and these properties are beneficial in controlling the process of aging. Also,
it is recommended for sore throat and vomiting. Moreover, it
has antimicrobial potential as well which can help in treating
infectious diseases and helminthiasis (Jiang et al., 2006; Shukla
and Singh, 2007; Ali et al., 2008; Nicoll and Henein, 2009). Its
health benefits have been discussed in subsequent sections.

GINGER AND ANTIOXIDANTS

The rich phytochemistry of ginger includes components that
scavenge free radicals produced in food chains or biological
systems. Some free radicals generated during the process of
oxidation are essential for energy production (Ramaa et al.,

385

2006). Increased production of free radicals and reduction in

cellular homeostasis results in a condition known as oxidative
stress that can lead to DNA damage (Hussein et al., 2005).
In such circumstances of imbalance, extra antioxidant supplementation through dietary modules is essential for organism
vitality (Barta et al., 2006). Ginger is one of the richest sources
of antioxidants that paved the way for its utilization to scavenge
free radicals and allied health discrepancies. The active ingredients of ginger include gingerols, which exhibit antioxidant
activity as determined through in vitro studies (Kikusaki and
Nakatani, 1993). Furthermore, enzymes such as xanthine oxidase are involved in the generation of reactive species and their
inhibition has been documented regarding gingerols (Chang
et al., 1994). The bioactive molecules of ginger like gingerols
have shown antioxidant activity in various modules (Dugasani
et al., 2010).
At times, in experimental rodents, chemicals have been used
to initiate the production of free radicals in the body. Rat modeling showed that ginger significantly lowered induced lipid
peroxidation and raised the levels of antioxidant enzymes, together with serum glutathione (El-Sharaky et al., 2009). Kota
et al. (2008) studied the effects of ginger at 0.5, 1, and 5 and
their findings indicated significant reduction in MDA in liver and
kidney tissues. The appropriate justifications regarding these effects include enhancement of the antioxidant status of the host
tissue or inhibition of oxidative products. Likewise, a synthetic
analogue of zingerone (Dehydrogingerone) showed mild inhibition of lipid peroxidation by scavenging free radicals (Rajkumar
and Rao, 1993). Additionally, feeding dietary ginger at 1% w/w
during administration of malathion (20 ppm) for 4 weeks significantly attenuated malathion-induced lipid peroxidation and
oxidative stress in rats (Ahmed et al., 2000). Later, concomittant dietary feeding of ginger (1%w/w) significantly attenuated
lindane-induced lipid peroxidation, accompanied by the modulation of OFR-scavenging enzymes as well as reduced glutathione (GSH) and the GSH-dependent enzymes glutathione
peroxidase (Gpx), glutathione reductase (GR), and glutathioneS-transferase (GST) (Ahmed et al., 2008).
The functional ingredients of ginger like gingerols possess
substantial antioxidant activity as determined by various antioxidants assays. In the antioxidant activity assay, [6]-gingerol,
[8]-gingerol, [10]-gingerol, and [6]-shogaol exhibited substantial scavenging activities with IC50 values of 26.3, 19.47, 10.47,
and 8.05 muM against DPPH radical. IC50 values of 4.05, 2.5,
1.68, and 0.85 muM against superoxide radical and IC50 values
of 4.62, 1.97, 1.35, and 0.72 muM against hydroxyl radical, respectively (Dugasani et al., 2010). In vitro, zingerone scavenged
O2 - and OH and suppressed lipid peroxidation. The effects of
zingerone treatment in this model suggest possible value in the
treatment of Parkinsons disease (Kabuto et al., 2005). Likewise,
[6]-shogaol also attenuated the lipopolysaccharide-induced upexpression of iNOS and COX-2 in murine macrophages (Pan
et al., 2008).
The antioxidative properties of ginger and its components
have been explored in various in vitro and in vivo test systems.

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M. S. BUTT AND M. T. SULTAN

Strengthening the bodys defenses by improving the antioxidant

status will undoubtedly protect against the oxidative stress involved in the etiology of many chronic diseases (Shukla and
Singh, 2007).

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CANCER INSURGENCE AND GINGER

There are many reasons for the pathogenesis and progression
of cancer; however, it is hypothesized that cancer insurgence can
be minimized through diets rich in bioactive molecules (Butt and
Sultan, 2009). A number of research investigations unveiled the
therapeutic role of culinary herbs against malignancy, including garlic, black cumin, etc. (Butt et al., 2009; Butt and Sultan,
2010). Despite the potential efficacy of ginger in chemoprevention, the mechanism by which it affects this chemoprevention
remains a matter of conflict among researchers. Ginger, owing
to its functional ingredients like [6]-gingerol, [6]-shogaol, [6]paradol, and zerumbone, exhibits anti-inflammatory and antitumorigenic activities (Jeong et al., 2009; Hung et al., 2009). Ginger and its bioactive molecules are effective in controlling the
extent of colorectal, gastric, ovarian, liver, skin cancers (Ishiguro et al., 2008; Sung et al., 2008; Brown et al., 2009; Kim
et al., 2009; Jeong et al., 2009). Some recent works related to
anticancer perspectives have been presented in Table 3. Furthermore, several research investigations also support the fact that
ginger can cure breast and prostate cancers (Lee et al., 2008;
Sung et al., 2009).
Colorectal cancer is more prevalent in vegetarians and the
intake of ginger has been found to be effective in reducing
the extent of this menacing disease. Manju and Nalini (2005)
studied the efficacy of ginger against 1,2 dimethylhydrazine
(DMH)-induced colon cancer. They observed that ginger supplementation at 50 mg/kg body weight/day suppresses colon
Table 3

carcinogenesis by enhancing the activities of various enzymes,

e.g., glutathione peroxidase (GPX), glutathione-S-transferase
(GST), and glutathione reductase (GR). In this context, Jeong
et al. (2009) further showed that [6]-gingerol is effective in
suppressing in vivo tumor growth in nude mice, an effect that
was mediated by the inhibition of LTA(4)H activity in HCT116
colorectal cancer cells (Lee et al., 2008; Brown et al., 2009).
Likewise, Kim et al. (2009) administered Zerumbone (ZER)
at 100, 250, and 500 ppm orally in preclinical mouse models
and observed inhibition in multiplicity of colonic adenocarcinomas along with suppressing colonic inflammation in a dosedependent manner. The mode of action includes inhibition of
proliferation, induction of apoptosis, and suppression of NF-B
and heme oxygenase (HO)-1 expression. It also stems cIAP1
expression that is helpful in the induction of apoptosis. In an
earlier study by Nakamura et al. (2004) significant increase in
glutathione S-transferase concentrations was observed because
of ZER treatment. They further reported that ZER induces nuclear localization of the transcription factor Nrf2, which holds
the ability to bind the antioxidant response element (ARE) of
the phase II enzyme genes. This suggests that ZER is a potential
activator of the Nrf2/ARE-dependent detoxification pathway
helpful in the chemo-preventive potential of ginger against colorectal cancer (Chung et al., 2009). Earlier, Murakami et al.
(2002) reported that ZER inhibits the proliferation of human
colonic adenocarcinoma cell lines in a dose-dependent manner
and brings apoptosis in COLO205 cells, as detected by dysfunction of the mitochondria transmembrane, Annexin V-detected
translocation of phosphatidylserine, and chromatin condensation. Likewise, [6]-shogaol inhibits the growth of human colon
cancer cells (COLO 205) and induces apoptosis through modulation of mitochondrial function regulated by reactive oxygen
species (ROS), preceding cytochrome c release, caspase activation, and DNA fragmentation. They also observed [6]-that
shogaol-treated COLO 205 cells exhibited up-regulation of Bax,

Recent evidences for anticancer perspectives of ginger

Sr. # Research Group and Year

Cancer Types

Model used

Component of interest

1
2
3

Jeong et al., 2009

Hung et al., 2009
Yodkeeree et al., 2009

Colon cancer
Lungs cancer
Colon cancer

In vivo in nude mice

[6]-Gingerol
Cell culture study
6-Shogaol
Human colon cancer cells Zerumbone

4
5
6

Nigam et al., 2009

Sung et al., 2009
Habib et al., 2008

Skin cancer
Osteoclastogenesis
Liver cancer

Mouse model
Mouse monocyte
Male Wistar rats

Kim et al., 2008

Colon and lung cancer Preclinical mouse models Zerumbone

Ishiguro et al., 2007

Gastric cancer

Gastric cancer cells

6-gingerol 6-shogaol

Lee et al., 2008

Breast cancer

Human cell lines

[6]-Gingerol

10

Rhode et al., 2007

Ovarian cancer

Human ovarian cancer

cell lines

Ginger and
[6]-Gingerol

[6]-gingerol
Zerumbone
Ginger extract

Mechanism of action
Inhibition of LTA(4)H activity
Inhibition of AKT
Activation of extracellular signal-regulated
kinase 1/2 p38 mitogen-activated protein
kinase leading to DR4 and DR5
Apoptotic potential
Block RANKL-induced NF-kappaB activation
Reduced the elevated expression of NF-B and
TNF-
Suppresses modulatory mechanisms of growth
and induce apoptosis Reduce expression of
NF-B and HO-1
6-gingerol inhibit TRAIL-induced NF-B
activation 6-shogaol alone reduces viability
by damaging microtubules
Inhibits cell adhesion invasion motility and
activities of MMP-2 and MMP-9
Inhibition of NF-B activation

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GINGER AND ITS HEALTH CLAIMS

Fas, and FasL, with concurrent down-regulation of Bcl-2 and

Bcl-X (Pan et al., 2008).
In gastric cancer, the tumor necrosis factor-related apoptosisinducing ligand (TRIALS) plays a critical role by inducing apoptosis. Cascades of caspase proteins activate and deactivate owing to ginger and its functional components (Yodkeeree et al.,
2009). The major component of ginger, [6]-gingerol, increased
the TRAIL-induced apoptosis and activation of caspase-8 that
further triggers the release of Cyt-c from mitochondria leading to caspase-9 activation. The mode of action in such cases
also includes inhibition of NF-B via impairment p65 nuclear
translocation (Wei et al., 2005). Accordingly, Ishiguro et al.
(2007) introduced a model for [6]-gingerol and [6]-shogaol action against gastric cancer cells. They observed that [6]-gingerol
inhibits TRAIL-induced NF-B activation by impairing the nuclear translocation of NF-B, suppresses cIAP1 expression, and
increases TRAIL-induced caspase-3/7 activation. On the other
hand, [6]-shogaol damages microtubules, arrests cell cycle in
G2+M phases, and reduces viability in a casepase-3/7 independent manner. Despite all efforts, skin cancer incidence and
prevalence is constantly on the increase and a search for newer
and better agents for protection and treatment is required. [6]gingerol leads to up-regulation of Cytochrome-c and Apaf-1
subsequently culminating in triggering of the caspase cascade.
These firmly suggest that [6]-gingerol can effectively be used
for the treatment of gastric cancer (Ishiguro et al., 2007).
Yagihashi et al. (2008) reported that [6]-gingerol inhibited
both proliferation and invasion of hepatoma cells in a dosedependent manner at concentrations of 6.25200 muM (proliferation) and 50200 muM (invasion). Suppression of hepatoma
cell proliferation by [6]-gingerol may be due to cell cycle arrest
and apoptosis induction. The cell cycle arrest is also dependent upon microtubules. Previous studies have indicated that
the microtubule damage affects activities of various protein kinases and the expression of upstream genes of apoptosis, leading to apoptosis via a caspase-3/7-dependent or independent
pathway (Ishiguro et al., 2007). Similarly, Chen et al. (2007)
indicated that [6]-shogaol induces apoptosis by depleting glutathione (GSH) in Mahlavu cells, a human hepatoma subline.
Later, Habib et al. (2008) suggested that ginger extract (100
mg/kg body weight) holds the ability to reduce the elevated
expression of NF-B and TNF-alpha in rats with liver cancer.
Though tumor promotion is closely associated with inflammation and oxidative stress, it is likely that a compound with
a strong inhibitory effect on the arachidonic acid metabolism
would have anti-tumor promoting potential. For example, topical application of ginger extract 30 min prior to TPA leads to
dramatic protection against DMBA-initiated skin carcinogenesis in SENCAR mice and suppressed TPA-caused induction of
epidermal ODC and its mRNA expression, as well as cyclooxygenase COX, and lipoxygenase activities (Katiyar et al., 1996;
Park et al., 1998). Inhibition of angiogenesis through suppression of IjB degradation in the mouse skin proved ginger useful
in the treatment of skin cancer (Kim et al., 2005). [6]-Gingerol
treatment at 250, 300, and 350 M exhibited considerable

387

cytotoxicity as indicated by the growth inhibition of human

epidermoid carcinoma A431 cells mediated via reactive oxygen
species (ROS) induced apoptosis of 16.27, 20.54, and 29.52%,
respectively. As these effects decreased in mitochondrial membrane potential (MMP), further leading to subsequent apoptosis
of cancerous cells, they became more pronounced (Nigam et al.,
2009). In this regard, Lee et al. (2008) suggested that ingestion
of ginger at 250 mg/day can/may provide substantial quantities
of [6]-gingerol and its derivatives, namely 10 M, that may be
useful for preventing or treating breast cancer. Likewise, [6]Paradol is another principle component attributed to anticancer
perspectives against skin cancer as it attenuates carcinogenesis
and TPA-induced ear edema in female ICR mice (Surh et al.,
1999; Keum et al., 2002).
The effectiveness of ginger and its functional ingredients has
been demonstrated in a number of research investigations like
for ovarian cancer. Vijaya Padma et al. (2007) attributed such
properties to ROS production. Similarly, Rhode et al. (2007)
found that in vitro, ginger inhibits NF-B activation as well as
diminished the secretion of VEGF and IL-8 helping in the treatment and prevention of ovarian cancer via inhibition of growth
and modulation of angiogenic factors. Kyung et al. (2006) have
reported that [6]-shogaol mitigates apoptosis in the experimental
spinal cord injury. Azoxymethane-induced intestinal carcinogenesis in rats was significantly suppressed by dietary administration of gingerols (Yoshimi et al., 1992). CXC chemokine
receptor 4 (CXCR4) mediates the proliferation of tumor cells
to specific organs. The down-regulation of CXCR4 expression
would have potential against cancer metastasis. The zerumbone
down-regulated CXCR4 owing to transcriptional modifications,
i.e., it down-regulated mRNA expression, inhibited NF-B activity, and suppressed chromatin immunoprecipitation activity.
Suppression of CXCR4 expression by zerumbone correlated
with the inhibition of CXCL12-induced invasion of both breast
and pancreatic cancer cells (Sung et al., 2008). ZER is also an effective blocker of the receptor activator of nuclear factor-kappaB
(NF-kappaB) ligand (RANKL)-induced NF-kappaB activation
and of osteoclastogenesis induced by RANKL and tumor cells,
suggesting its potential as a therapeutic agent for osteoporosis
and cancer-associated bone loss (Sung et al., 2009). -elemene
is another component of ginger reported to hold anticancer
potential. It enhances the caspase-3, -7, and -9 activities, and
decreases Bcl-2 expression, thereby resulting in cytochrome c
release in non-small-cell lung cancer (NSCLC) and all these
processes lead to apoptosis (Wang et al., 2005).
Ginger may act as an anti-cancer and anti-inflammatory
agent by inactivating NF-B through the suppression of the
pro-inflammatory TNF-alpha. Evidence pertaining to anticancer
properties of ginger and its components are quite conclusive.
The molecular targets involved in chemoprevention like inhibition of NF-B activation via impairing nuclear translocation,
suppresses cIAP1 expression, increases caspase-3/7 activation,
arrests cell cycle in G2 + M phases, up-regulates Cytochromec, Apaf-1, activates PI3K/Akt/I kappaB kinases IKK, suppresses cell proliferation, and induces apoptosis and chromatin

388

M. S. BUTT AND M. T. SULTAN

condensation. Its functional ingredients like gingerols, shogaol,

and paradols are the valuable ingredients which can prevent
various cancers. However, results pertaining to anticancer perspective have mostly been taken from cell-culture studies or
animal models, therefore urgent studies are needed to elucidate the exact mechanism of action and their relevance for their
potential application to prevent and cure cancers in humans.

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GINGER AND IMMUNONUTRITION

Dietary patterns are major influential factors involved in the
proper functionality of the immune system. Among some newer
concepts in the domain of nutrition, immunonutrition is linked
with the role of certain nutrients in bringing a balance in the
human immune system. Immunonutrition, often based on the
principle to have a diet that can improve the immune system,
maintains homeostasis, and helps to fight against foreign and
malignant cells. Many studies have indicated that diet influences
the various intrinsic and extrinsic factors of the immune system
(Lin and Karin, 2007; Bourgeon et al., 2007). Chronic (or acute)
inflammation is a multi-step process mediated by activated inflammatory or immune cells (Grip et al., 2003). The hallmark
of most immune boosters remained in their anti-inflammatory
perspectives and reduction in the toxicity of certain ingested
chemicals (Butt et al., 2009).
In ancient times medical practitioners focused on herbs and
spices for improving the body systems. In many cultures ginger
and its products when consumed boost the immune system. In
addition, it has many other proclaimed beneficial effects. (Barta
et al., 2006). The anti-inflammatory potential of ginger has been
demonstrated in a number of scientific investigations. In this
context, Guh et al. (1995) reported concentration-dependent
inhibition of arachidonic acid-induced platelet aggregation and
formation of thromboxane B. Gingerol, shogaol, and other
structurally-related substances in ginger inhibit prostaglandin
and leukotriene biosynthesis through suppression of 5lipoxygenase or prostaglandin synthetase. Ginger also holds the
ability to inhibit synthesis of IL-1, TNF-, and IL-8, considered
as pro-inflammatory cytokines. The mechanism behind this
inhibition involves genes encoding (Tjendraputra et al., 2001;
Verma et al., 2004). In another investigation, Pan et al. (2008)
showed that [6]-shogaol down-regulates inflammatory iNOS
and COX-2 gene expression in macrophages by inhibiting
the activation of NF-B by interfering with the activation
PI3K/Akt/I kappaB kinases IKK and MAPK.
Inflammation results in the onset of several maladies, for example, gout and neurogeneative disorders. These ailments result
in enhanced production of several inflammatory cytokines and
prostaglandins. It is possible to control excess production of
such metabolites with the help of ginger and its active ingredients. Jung et al. (2009) indicated that Rhizome hexane fraction
extract of Zingiber officinale Roscoe (ginger hexan extract or
GHE) significantly inhibited the excessive production of NO,

PGE(2), TNF-alpha, and IL-1beta in LPS-stimulated BV2 cells.

The molecular mechanisms that underlie GHE-mediated attenuation are related to the inhibition of the phosphorylation of
three mitogen-activated protein kinases (MAPKs), extracellular
signal-regulated kinases 1 and 2 (ERK1/2), p38 MAPK, and cJun N-terminal kinase (JNK), and the activation of NF-B. Ginger rhizome contains potent compounds capable of inhibiting
allergic reactions and may be useful for the treatment and prevention of allergic diseases (Chen et al., 2009). The activation
of NF-B is linked to a variety of inflammatory diseases, including cancer, atherosclerosis, myocardial infarction, diabetes,
allergy, asthma, arthritis, Crohns disease, multiple sclerosis,
Alzheimers disease, osteoporosis, psoriasis, septic shock, and
AIDS (Aggarwal and Shishodia, 2006). Its inactivation or balanced expression is essential for the proper functioning of the
immune system. Ginger and its components have been reported
to possess the ability of reduced expression via modulation of
protein kinases, etc. (Zhou et al., 2006). Lee et al. (2009) used
lipopolysaccharide (LPS)-stimulated macrophages to study the
anti-inflammatory effects of 6-gingerol. They observed that its
reduction could decrease inducible nitric oxide synthase and
TNF-a expression through suppression of I-jBa phosphorylation, NF-jB nuclear activation, and PKC-a translocation.
Gout is a rheumatic disease of joints and the functional
ingredients of ginger including [6]-shogaol, owing to its strong
anti-inflammatory and antioxidant effects, can be used as
curative agents (Grzanna et al., 2005; Sabina et al., 2010).
Likewise, intraperitoneal injections of ginger extract decreased
the number of eosinophils along with diminished levels of
IL-4, IL-5, and eotaxin levels in the lungs (Ahui et al., 2009).
Further evidence can also be presented in this regard and
intraperitoneal administration of [6]-gingerol (25 mg/kg-50
mg/kg) produced an inhibition of acetic acid-induced writhing
response and formalin-induced licking time in the late phase.
However, higher doses of [6]-gingerol (50 mg/kg-100 mg/kg)
inhibited paw edema induced by carrageenin (Young et al.
2005). Ginger essential oil recovered the humoral immune
response in immunosuppressed mice (Carrasco et al., 2009).
The immune system also helps the body by protecting
it from the hazardous effects of chemicals. In this regard,
ethanol-induced toxicity is of prime importance. In rat modeling studies, some chemicals like bromobenzene have been
employed to induce hepatotoxicity. In one such study, the pretreatment of ginger extract prior to chemical-induced toxicity alleviated its toxic effects. The ginger extract improved
the activities of the antioxidant enzymes like SOD, GPx, and
the GSH level. Additionally, reduction in the activities of GR
and GSTs and Cyt P450 also supported the hypothesis that
ginger and its functional ingredients are helpful in overcoming
the toxicity arising due to chemicals via modulation of enzymes
(El-Sharaky et al., 2009). In this context, excessive consumption
of alcohol is also a risk factor contributing to many disorders
like liver necrosis. Shati and Elsaid (2009) postulate that water
extracts of ginger have detoxifying and antioxidant effects, and
these help to overcome alcohol-induced liver toxicity. Thus it

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GINGER AND ITS HEALTH CLAIMS

can be observed that ginger and its components possess antiinflammatory activities and can reduce the chemical toxicity in
organs like liver.
A conclusive approach drawn from this section of the paper is that anti-inflammatory responses of ginger components
include inhibition of prostaglandin and leukotriene biosynthesis and suppression of 5-lipoxygenase. Furthermore, inhibition of phosphorylation of three mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases 1 and 2
(ERK1/2), and c-Jun N-terminal kinase (JNK) are also important. The results are of significant importance in treating disorders like asthma, gout, arthritis, etc. However, cohort studies and
controlled trails need to be conducted as these would be helpful for dieticians to warrant the pharmacological applications of
ginger.

GINGER AND CARDIOVASCULAR PROTECTION

Cardiovascular disorders (CVD) are a major cause of morbidity and mortality in the world. The changing lifestyles and
dietary patterns are major contributory factors in the prevalence
and pathogenesis of CVD (Matsuura et al., 2008). Ginger and its
functional ingredients play many roles in improving the cardiovascular health of individuals. At a molecular level, it reduces
retinoid binding protein (RBP) mRNA expression levels in the
liver and visceral fat resulting in improved lipid metabolism
(Matsuda et al., 2009).
Epidemiological studies have indicated that elevated blood
pressure is one of the major risk factors for stroke and coronary heart disease (CHD). In recent years, several herbal remedies are in use and ginger and its combinations with other
herbs are of significant importance (Chen et al., 2009). Ghayur
et al. (2005) demonstrated in a research study that the aqueous
extract of fresh ginger lowers BP via endothelium-dependent
(cholinergic) and endothelium-independent (CCB) vasodilator
pathways. They reported the emergence of some cardiotonic
component due to ginger supplementation that was sensitive to
the blockade of Ca++ release in the presence of the cholinergic
receptor blockade. Previous studies showed that the cholinergic component is usually concentrated in the aqueous while
the CCB component is concentrated in the less polar extracts
(Ghayur and Gilani, 2005; Abdel-Aziz et al., 2006).
Apart from ginger itself, some of the pure compounds of
ginger, [6]-gingerol and [6]-shogaol, have been studied for their
effects on BP in laboratory animals and both produced a depressant effect. Later reports revealed that the peripheral pressor
effect of [6]-shogaol in rats is caused by the release of a peptidelike substance from the sympathetic nerve endings (Suekawa
et al., 1984).
Ansari et al. (2006) reported that treatment with an ethanolic
extract of ginger in isoproterenol-treated rats increased the
levels of endogenous myocardial antioxidants (catalase, superoxide dismutases, and tissue glutathione), decreased the levels
of serum marker enzymes (LDH, creatinine kinase, aspartate

389

aminotransferase, and alanine aminotransferase), and increased

myocardial lipid peroxides. The cardioprotective property
of ginger, further confirmed by histological examination,
demonstrated that ginger treatment largely protected rats from
isoproterenol-induced myocardial injury.
Some of the known pungent constituents of ginger including [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol
hold vasodilator activity; [6]-shogaol exhibited only a mild vasodilator effect as compared to gingerols (Kimura et al., 1988).
It is possible that the cholinergic-mediated vascular effects
of ginger are due to sesquiterpenes such as zingiberene, bisabolene, camphene, and phellandrene (Langner et al., 1998).
Alizadeh-Navaei et al. (2008) evaluated the potential of ginger in improving lipid profile and according to their observation, 3 g/day in three equal doses resulted in marked decrease
in triglyceride, cholesterol, low-density lipoprotein (LDL), and
very low-density lipoprotein (VLDL). There were several compounds, including [6]-gingerol, [8]-gingerol, [6]-shogaol, and
[10]-gingerol, that bound to the thrombocytes, and all had shown
anti-platelet aggregation activities (Nie et al., 2008). Dias et al.
(2006) contradicted the findings of other scientists and observed
that ginger supplementation did not improve lipid profile significantly. The improvement in lipid profile as a function of ginger
is dependent on reduced cholesterol biosynthesis in liver and
stimulated the conversion of cholesterol to bile acids and the
excretory system (Verma et al., 2004).
The present discussion concludes that ginger is of significant importance in improving lipid profile and its blood pressure lowering ability is indeed imperative in controlling the extent of hypertension, arthrosclerosis, and allied cardiovascular
disorders.

GINGER FOR DIGESTIVE HEALTH

It facilitates the transport of nutrients and phytochemicals
into the blood stream for their delivery to body cells. Dietary factors also influence the frequency and severity of gastrointestinal
disorders including gastro-esophageal reflux disease (GERD),
diverticular disease, and Crohns disease. The balanced diets improve the health of individuals, and herbs/spices are important
in this regard. It has also been reported that ginger can interfere
with the activities of some digestive enzymes. Ramakrishna Rao
et al. (2003) demonstrated that ginger enhanced the activity of
pancreatic lipase and amylase.
Since times immemorial, ginger and its formulations have
been used as traditional remedies for gastric disturbances. Research investigations in the domain of pharmaceuticals and nutrition explored the significant association of ginger and its role
in improving the functionality of the gastrointestinal tract. Nanjundaiah et al. (2009) studied the ulcer-preventive properties
of the aqueous extract of ginger rhizome at 200 mg kg1 body
weight; it reduces the swim stress-/ethanol stress-induced ulcers
up to 7786% and its effects were similar to that of lansoprazole (80%) at 30 mg kg1 body weight. Ulcerative colitis is one

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M. S. BUTT AND M. T. SULTAN

gastrointestinal ailment characterized with inflammatory responses. Tumor necrosis factor- (TNF-) amplifies the inflammatory response by activating a cascade of immune responses
(Ardizzone and Bianchi, 2005). This cytokine also stimulates
the production of other cytokines, arachidonic acid metabolites,
and proteases (Jainu et al., 2006). Inhibition of PGE2, on the
other hand, may follow that of TNF- or may result from GE
ability to inhibit cycloxygenase enzymes. El-Abhar et al. (2008)
stated that ginger extract can indeed reduce the onset of ulcerative colitis owing to its functional ingredients (Young et al.,
2005; Grzanna et al., 2005).
Ginger also helps in enhancing the growth of bacteria residing
in the gastrointestinal tract. Recently, Sutherland et al. (2009)
showed that aqueous extracts of garlic significantly enhanced
the growth of L. reuteri while inhibiting both pathogenic strains
of E. coli. The results are quite conclusive that ginger helps in
improving the health of gastrointestinal tracts.

MISCELLANEOUS HEALTH BENEFITS

In the last few years, the health-promoting potential of ginger has been largely explored and it is considered to be safe
as a herbal medicine. Diabetes mellitus and its complications
are one of the leading causes of death in the world. According to one estimate, at the end of the year 2030, this disease
will affect approximately 376 million people worldwide (Wild
et al., 2004; Lapshina et al., 2006). Some research studies have
presented the effectiveness of ginger against diabetes and its
complications. Weidner and Sigwart (2000) conducted an acute
(64 days) experimental study and suggested that a patented ginger extract (25100 mg/kg) with a high content of gingerols and
shogaols did not induce significant changes in blood glucose,
blood coagulation, blood pressure, and heart rate in normal male
rats. However, the effects have been more pronounced in hyperglycemic rats, for example, in animals that are diabetic, deficient
in the apolipoprotein E gene or those that have been fed a high
lipid diet. In these animals, ginger significantly lowered blood
glucose, serum total cholesterol, LDL, VLDL, and triglycerides,
and raised HDL (Fuhrman et al., 2000).
Later, Bhandari et al. (2005) postulated that ethanolic extract of Zingiber officinale (200 mg/kg) fed orally for 20 days
produced a significant antihyperglycaemic effect (P < 0.01) in
diabetic rats and the results were comparable to a standard antihyperglycaemic agent, namely gliclazide (25 mg/kg, orally).
Likewise Han et al. (2005) demonstrated that an aqueous extract of ginger inhibited the hydrolysis of triolein emulsified
with phosphatidylcholine by pancreatic lipase in vitro and reduced the elevation of rat plasma triacylglycerol levels after oral
administration of a lipid emulsion containing corn oil. Furthermore, Nammi et al. (2009) assert that the ethanolic extract of
ginger at 100, 200, and 400 mg/kg body weight reduced body
weights and levels of glucose, insulin, total cholesterol, LDL
cholesterol, triglycerides, free fatty acids, and phospholipids in
high-fat diets (Ojewole, 2006). Recently Heimes et al. (2009)

supported the hypoglycemic potential of ginger. Islam and Choi

(2008) suggested that ginger has insulinoptropic properties that
are mainly attributed to its glucose-lowering potential (Sekiya
et al., 2004; Goyal and Kadnur, 2006; Heimes et al., 2009).
Herbal remedies are becoming important in pregnancyinduced disorders such as nausea, vomiting, insomnia, and
morning sickness. Although, the pharmaceuticals are in use
yet many people prefer herbal remedies owing to their safe
status (Holst et al., 2009). According to Ozgoli et al. (2009),
ingestion of 1000 mg of ginger/daily can serve as a means to
decrease pregnancy-induced nausea and vomiting. Moreover,
ginger, along with higher amounts of protein intake, can delay
the onset of nausea in pregnancy and chemoprevention (Levine
et al., 2009). In this regard, Ensiyeh and Sakineh (2009) stated
that ginger is more effective than other nutritional therapies, for
instance, vitamin B6, for relieving the severity of nausea and
vomiting episodes in pregnancy.
Ginger and its preparations are rich in antioxidant compounds that are effective in reducing the extent of diabetes
mellitus, pregnancy-induced maladies, arthritis, etc. It is considered a safe herbal medicine with only a few and insignificant
adverse/side effects. More studies are required in animals and
humans to study the kinetics of functional ingredients of ginger.
Additionally, the safety studies should be carried out over extended period of time thus to present comprehensive evidences
for meticulousness.

CONCLUSIONS
Natural products are gaining attention owing to their rich phytochemistry and risk-free use. The plant-based functional and
neutraceutical foods enriched with biomolecules have been capturing a major share of the global nutrition market. A number of
plants are explored in this context; ginger holds a unique composition and FDA ranked it in the GRAS list. The health-promoting
perspectives of ginger are well known. It can treat a wide range
of ailments including immunonutrition and anti-inflammatory
responses. Likewise, the anticancer potential of ginger is well
documented and its molecular aspects embrace induction of
Phase 2 enzymes, inhibition of post-translational modification,
angiogenesis and metastasis, induction of apoptosis, and inhibition of cell-cycle progression. Besides these, it improves
cardiovascular disorders, diabetes mellitus, and gastrointestinal
health. Undoubtedly, we have presented a great deal of evidence
in this article and it seems to favor ginger but some ambiguities
necessitate further research before claiming its efficacy.

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