Introduction to ginger

Ginger, the rhizome of Zingiber officinale Roscoe, is one of the most widely used spices and a
traditional remedy for pain, inflammation, and gastrointestinal disorders. Ginger essential oil has
antibacterial, antiviral, and antifungal properties. The rhizomes of the plants have a strong aroma
and are widely used as a spice and medicine. The present study reports a detailed drug screen of
ginger evaluating its antioxidant, anti-inflammatory, and ant nociceptive properties. This study
should shed additional light on the pharmacological and medicinal properties of ginger oil.

History

Precise information about the origin of the plant has been lost, due to its long history of
cultivation in these regions, including Southeast Asia. The history of ginger is mentioned in the
earliest records of Chinese herbs and is firmly embedded in the culinary and medicinal practices
of the natives of Asian countries. The plant was well known to the Greeks and was mentioned by
the ancient Greek physician, botanist, and pharmacist discoveries (40 - 90 AD), in his works.
After an orgy, the Greeks ate ginger wrapped in bread to fight nausea .The Roman writer,
naturalist, and philosopher Pliny (AD 23-7979), known as Pliny the Elder, also described the
medicinal use of ginger in his works, Naturalis Historia (Elzebroek and Wind, 2008).Throughout
the Middle Ages, ginger was used to flavor beer. English botanist William Roscoe named the
plant Zingiber officinale in 1807. The genus name comes from the Greek word 'zingiberis',
which derives from the Sanskrit word 'shringavera', which aptly means ‘shaped like the horns of
a stag’, while officinate relates to the medicinal properties of the rhizomes (Elzebroek and Wind,
2008). Ginger is grown commercially around the world and is a common crop in Africa, Latin
America, and southeast-Asia.
Ginger teas are renowned folk remedies in many countries for a wide range of conditions, but
mainly for treating coughs, colds and flu (Khaki and Fathiazad, 2012). Beer containing ginger is
used to calm stomach ailments .In Burma, a mixture of ginger and palm juice is used to relieve
the flu ,while in Colombia, ginger mixed with hot panela is used to treat colds and flu. To relieve
colds ,an infusion of ginger rhizomes with brown sugar is given , while scrambled eggs with
powdered ginger in china are taken as a home remedy to reduce cough . A mixture of ginger and
mango juice is considered a panacea ( a medicine to cure everyone ) in congo. Khaki and
Fathiazad (2012) also mention the use of ginger rhizomes, prepared as a paste, for external
application to treat headaches and taken orally to offer cold relief in India and Nepal, while that
the mixture with lemon and black salt is widely used to combat nausea. In Indonesia, ginger is
believed to reduce fatigue, prevent reeumatism and improve digestion, while in the Philippines it
is taken to soothe sore throats .In the united states ,ginger is used as a remedy to relieve motion
sickness and morning sickness during pregnancy and to reduce heat cramps. Peruvians take
ginger tea to reduce stomach cramps, while the Japanese use ginger to improve blood
circulation.Ginger plays an important role in traditional Ayurvedic, Chinese, Arabic and African
medicines used to treat headaches, nausea, colds, arthritis, rheumatism, ,muscle disorders and
inflammation (Baliga et al. , 2011; Dehghani et al., 2011).

Components

Ginger is known for its nutraceutical value, which can be attributed to a variety of bioactive
compounds, including gingerols, zingiberene, and shogaols (Butt and Sultan, 2011). The pungent
flavor of fresh ginger rhizome is due to the presence of Gingerols (GN), a group of volatile
phenolic compounds. Gingerol (6GN) is the main compound in the rhizome responsible for the
spiciness, while other GNs, such as 4, 8, 10 and 12GN, and are present in lower concentrations.
These compounds are thermally labile and are transformed at high temperature into Shogaols
(SG), which impart a pungent and spicy odor (Wohlmuth et al., 2005). During the preparation of
dried ginger, GNs are also rapidly converted to the corresponding SG, of which 6SG is the most
common dehydration product (Ok and Jeong, 2012). In many cases, 6SG has been reported to
have better biological activities than 6GN. In the plant, NGs coexist with various analogues,
including gingers (Wang et al., 2011a). It was found that the concentrations of 6, 8, and 10GN
decreased when fresh ginger was roasted, dried, and charred, while the concentrations of 6SG
increased with the corresponding treatments (Zhang et al., 2012). Although some reports have
indicated that 6SG is found in the rhizome of fresh ginger (Wang et Ial., 2011b). This has not
been conclusively proven. Park and Jung (2012) developed a sensitive time-of-flight mass
spectrometry method for high-performance liquid chromatography for the quantification of
ginger-related compounds in fresh and dried ginger and hot water extract. They concluded that
the fresh ginger is devoid of shogaols, but suggested that these compounds are artifacts formed
by tanglers of the resolutionof football dehydration reactions.
 Medicinal uses and potential health benefits

Ginger as Traditional Medicine

Ginger contain direct anti-microbial activity and is used to treat bacterial infections (Tan and
Vanitha 2004). In Traditional Chinese Medicine, it is employed in colic and in atonic dyspepsia
and used as a stimulant (Keys 1985; Grant and Lutz 2000; Sharma 2017; Yilmaz et al. 2018).
Ginger is regarded as a Yang herb, which can decrease Yin and nourish the body (Jittiwat and
Wattanathorn 2012). Mishra et al. (2012) also revealed that ginger in Traditional Chinese
Medicine characterized as spicy and hot, and it is claimed to warm the body and treat cold
extremities, improves a weak and tardy pulse, address a pale complexion, and strengthen the
body after blood loss. In Traditional Chinese Medicine as herbal therapy against several
cardiovascular diseases (Wynn et al. 2001). Based on the historical usage of ginger as an
antiemetic agent in the East Traditional Medicine. The antiemetic effect of ginger has been
known as a treatment method in traditional medicine especially the Chinese and Iranian
Medicine (Eric Chan et al. 2011; Palatty et al. 2013; Naderi et al. 2016; Soltani et al. 2018).
Sharma (2017) explained that many of herbs and plant extracts such as ginger are based on what
has been used as part of Traditional Medicine Systems and there is a large body of anecdotal
evidence supporting their use and efficacy. Some other researchers emphasized that ginger plays
an important role in Ayurvedic, Chinese, Arabic and African traditional medicines used to treat
headaches, nausea, colds, arthritis, rheumatism, muscular discomfort and inflammation (Baliga
et al. 2011; Dehghani et al. 2011). Recently, ginger rhizomes are used in Traditional Medicine as
therapy against several cardiovascular diseases such as hypertension (Ghayur et al. 2005).
Niksokhan et al. (2014) reported that ginger has been used in Traditional Medicine of Iran as an
anti-edema drug and is used for the treatment of various diseases including nausea,
gastrointestinal disorders, respiratory disorders, athero-sclerosis, migraine, depression, gastric
ulcer, cholesterol; and other benefits of giner are reducing pain, rheumatoid arthritis,
antiinflammatory, and antioxidant effects. Surh et al. (1998), and Manju and Nalini (2010)
mentioned that ginger is one of the most widely used spices in India and has been utilised
frequently in traditional oriental medicine for common cold, digestive disorders and rheumatism.
Ursell (2000) and Oludoyin and Adegoke (2014) reported that ginger is a perennial plant with
narrow, bright green, grass-like leaves, and it is cultivated in the tropics for its edible rhizomes
and has been found to be useful for both culinary and medicinal purposes. Schwertner and Rios
(2007) reported that the main components of ginger are 6-gingerol, 6-shogaol, 8-gingerol, and
10-gingerol and these constituents have previously been shown to exhibit strong antioxidant
activity. 6-gingerol was reported as the most abundant bioactive compound in ginger with
various pharmacological effects including antioxidant, analgesic, anti-inflammatory and
antipyretic properties (Kundu and Surh 2009; Dugasani et al. 2010). The shogaols can be
partially transformed to paradols upon cooking or metabolised to paradols in the animals, body
after being consumed and absorbed by digestive system (Wei et al. 2017). Gingerol and shogaol
in particular, is known to have anti-oxidant and anti-inflammatory properties (Kim et al. 2005).

Ginger as Traditional Medicine

Ginger extract can remove disorders caused by oxidative stresses as a strong anti-oxidant. Studies have shown
that extant phenolic compounds and anthocyanins including gingerols and the sugevals had many neuro
protective effects such as analgesic effects, memory improvement, and learning caused by the aging process
(Fadaki et al. 2017). For culinary purposes ginger is suitable for all dished both sweet such as drinks, puddings,
apple pie, cakes, breads, candies, etc; and savoury such as soups, sauces, stews, savoury

puddings, grills, roasts, etc. (Oludoyin and Adegoke 2014). Oludoyin and Adegoke (2014) stated that the
active hypoglycaemic component of ginger was not affected by heat, hence, the consumption of ginger in raw
and cooked forms in different cuisines maybe an effective regimen in the management of diabetes. Simi- larly,
the medicinal uses of ginger are enormous such as exert anti-microbial, anti nausea (Portnoi et al. 2003), anti
pyretic (Suekawa et al. 1984), analgesic, anti-inflamma- tory, hypoglycaemic (Ojewole 2006; Young et al.
2005), anti ulcer, antiemetic (Mascolo et al. 1989), cardio tonic, anti-hypertensive (Ghayur and Gilani 2005),
hypolipi- demic (Al-Amin et al. 2006), anti-platelet aggregation (Bordia et al. 1997) effects in both laboratory
animals and human subjects. Turmeric is one of the main ingre- dients for curry powder, and used as an
alternative to medicine and can be made into a drink to treat colds and stomach complaints (Chan et al. 2009).
In folk medi- cine, turmeric has been used in lowering blood pressure and as tonic and blood purifier (The
Wealth of India 2001). Phytochemical investigation of several types of ginger rhizomes has indicated the
presence of bioactive compounds, such as gingerols, which are antibacterial agents and shogaols,
phenylbutenoids, diarylheptanoids, flavanoids, diterpenoids, and sesquiterpenoids (Siva- sothy et al. 2011; El
Makawy et al. 2019). It has been proved in some researches that ginger leaves has great potential to be
developed into functional foods and other health products, because it has higher antioxidant activity than
rhizomes and flowers (Park et al. 2014). When compared to the Indian varieties, the Chinese ginger is low in
pungency and is principally exported as preserves in sugar syrup or as sugar candy (Govindar- ajan 1982).
Semwal et al. (2015) reported that an infusion of ginger rhizomes with brown sugar is administered to relieve
common colds, while scrambled eggs with pow- dered ginger is taken as a home remedy to reduce
coughing in China. While, ginger is used in the United States as a remedy to alleviate motion sickness and
morning sickness during pregnancy and to reduce hear cramps (Semwal et al. 2015). Furthermore, there are
many studies that proved their beneficial effects against the symptoms of diseases, acting as anti-inflam-
matory, anti-tumour, anodyne, neuronal cell protective, anti-fungal and anti-bacterial agent (Mesomo et al.
2012; Yassen and Ibrahim 2016). Various ginger com- pounds and extracts have been tested as anti-inflamma-
tory agents, where the length of the side chains determines the level of the effectiveness (Bartels et al. 2015).
But, a combination of ginger extracts is more effective in decreasing inflammatory mediators than an
individual compound (Lantz et al. 2007). The active ingre- dients in ginger are thought to reside in its volatile
oils (Aldhebiani et al. 2017). The major ingredients in ginger oil are bisabolene, zingiberene, and zingiberol
(Moghaddasi and Kashani 2012). Some other scientists noted that the interest in ginger is endorsed to its
several biologically active compounds content such as gingerol, shogaols, gingerdiol, gingerdione, α-zingiber-
ene, curcumin, and β-sesqui-phellandrene (Zhao et al. 2011). Ginger has been part of the folk medicine and
popular nutraceuticals (Bartels et al. 2015). Ginger con- sists of a complex combination of biologically active
con- stituents, of which compounds gingerols, shogoals and paradols reportedly account for the majority of its
anti- cancer inflammatory properties (Tjendraputra et al. 2001). 6-paradol was suggested as a therapeutic agent
to effectively protect the brain after cerebral ischemia, likely by attenuating neuroinflammation in microglia
(Gaire et al. 2015). Zinger officinale used as a condiment in several countries but also it acts as a treatment for
ail- ments; for instance, gastrointestinal disorders, colds, arthritis, hypertension and migraines (White 2007;
Hos- seini and Mirazi 2015). Maghbooli et al. (2014)

confirmed the efficiency of ginger powder in the therapy of common migraine attacks and its similarity to the
anti- epileptic drug. Many studies have reported that Ginger has useful effects to cancer prevention (Lee et al.
2008), also the treatment of nausea and vomiting due to preg- nancy and chemotherapy (Pongrojpaw et al.
2007; Ryan et al. 2012). The anti-spasmodic effect of Ginger is due to the blocked of cyclooxygenase and 5-
lipoxygenase (Van Breemen et al. 2011). Also, It has been reported that ginger lowers blood pressure through
blockade of voltage-dependent calcium channels (Ghayur and Gilani 2005). Khaki et al. (2012) reported that
ginger has a protective effect against DNA damage induced by H2O2 and maybe promising in enhancing
healthy sperm parameters. In Iran, traditionally ginger rhizome was used for enhancing male sexuality,
regulating female menstrual cycle, and also reducing painful men- strual periods (Hafez 2010). Adib Rad et al.
(2018) reported that ginger as well as Novafen is effective in relieving pain in girls with primary
dysmenorrhoea, and treatment with natural herbal medicine, non-synthetic drug, is recommended to reduce
primary dysmenor- rhoea. Karangiya et al. (2016) concluded that the sup- plementation of garlic improves the
performance of broilers when added at the rate of 1% of broiler and can be a viable alternative to antibiotic
growth promoter in the feeding of broiler chicken. Manju and Nalini (2010) found that ginger supplementation
to 1,2-dimethyl hydrazine (DMH) treated rats inhibited colon carcinogen- esis, as evidenced by the
significantly decreased number and incidence of tumours; in addition ginger optimised tissue lipid peroxidation
and antioxidant status in DMH treated rats. Dinesh et al. (2015) suggested that for growth promotion and
management of soft rot disease in ginger, GRB35 B. amyloliquefaciens and GRB68

S. marcescens could be good alternatives to chemical measures; they also recommend the use of

B. amyloliquefaciens for integration into nutrient and disease management schedules for ginger cultivation.
Mahassni and Bukhari (2019) found that the extract of ginger rhizome have different effects on cells and anti-
bodies of the immune system in smokers and non- smokers, although both benefited from enhancement of the
thyroid gland. In their research, it has been found that ginger maybe beneficial for smokers with anaemia,
while for non-smokers, it may lead to a stronger antibody response or humoral immunity against infec- tions.
Vemuri et al. (2017) found that aqueous natural extracts mixtures (NE mix) prepared from common spice like
ginger is a potential alternative therapeutic approach in certain types of cancer. Bartels et al. (2015) concluded
that ginger maybe considered as a part of the symptomatic treatment of osteoarthritis (OA),

where the patient is motivated for trying this nutraceuti- cal. Schnitzer (2002) mentioned that evidences is now
provided suggesting that it may have a place in the man- agement of OA of the knee, and coated ginger extract
maybe considered for this purpose in the future. Adib Rad et al. (2018) found that Ginger reduced menstrual
pain, and it is effective in relieving pain in girls with primary dysmenorrhoea; moreover, Drozdov et al. (2012)
mentioned that Ginger is a safe drug with minimal side effects. Sinagra et al. (2017) reported that ginger is an
effective non-pharmacological option for treating hyperemesis gravidarum with respect to the inherent
heterogeneity of the available studies. Gholam- pour et al. (2017) found that ginger extract appears to exert
protective effects against ferrous sulphate- induced hepatic and renal toxicity by reducing lipid peroxidation
and chelating iron. Atashak et al. (2014) mentioned that 10 weeks of either ginger supplemen- tation or
progressive resistance training (PRT) protects against oxidative stress and therefore both of these inter-
ventions can be beneficial for obese individuals. Jittiwat and Wattanathorn (2012) demonstrated that ginger
pharmacopuncture at GV20 can improve memory impairment following cerebal ischemia more rapidly than
acupuncture, and one probable mechanism under- lying this effect is improved oxidative stress. Yilmaz et al.
(2018) found the positive effects of ginger in folliculo- genesis and implantation. They have also found that
ginger may enhance implantation in rats in the long term with low dose. In other studies, the favourable out-
comes have been reported on the positive effects of ginger on male infertility and sperm indices (Khaki et al.
2012; Ghlissi et al. 2013). Akinyemi et al. (2016) described that dietary supplementation with both types of
rhizomes, namely ginger and turmeric, inhibited arginase activity and prevented hypercholesterolaemia in rats
that received a high-cholesterol diet. In con- clusion, these activities of ginger represent possible mechanisms
underlying its use in herbal medicine to treat several cardiovascular diseases. Amri and Touil- Boukoffa (2016)
concluded that Ginger has an important anti-hydatic effect in vitro, and this herbal product may protect against
host,s cell death by reducing the high levels of nitric oxide (NO). They finally suggest the prom- ising use of
ginger in the treatment of Echinococcus granulosus infection. Soltani et al. (2018) recommend administration
of oral ginger one hour before operation to control the severity of postoperative nausea and vomiting (PONV)
in patients undergoing laparoscopic cholecystetcomy. Daily et al. (2015) claimed that ginger root
supplementation significantly lowers blood glucose and HbA1c levels, and when combined with dietary and
lifestyle interventions, it maybe an effective

intervention for managing Type 2 diabetes mellitus. Islam et al. (2014) boiled ginger extracts can be used in
food preparation as well as against pathogenic bacteria during active infection. Viljoen et al. (2014) suggested
potential benefits of ginger in reducing nausea symp- toms in pregnancy. They have found that ginger could be
considered a harmless and possibly effective alterna- tive option for women suffering from nausea and vomit-
ing during pregnancy (NVP). Zaman et al. (2014) mentioned that ginger root extract significantly inhibited the
gastric damage and ginger root showed significant anti-ulcerogenic activity in the model studied, it can be a
promising gastro-protective agent. Willetts et al. (2003) concluded that ginger extract is a more effective
treatment than placebo for nausea and retching during pregnancy. Yadav et al. (2016) demonstrated that ginger
is one of the most commonly used spices and medicinal plants, and it is effective to improve diet- induced
metabolic abnormalities, however the efficacy of ginger on the metabolic syndrome-associated kidney injury
remains unknown. Naderi et al. (2016) stated that ginger powder supplementation at a dose of 1 g/d can reduce
inflammatory markers in patients with knee osteoarthritis, and it thus can be rec- ommended as a suitable
supplement for these patients. Mahmoud and Elnour (2013) discovered that ginger has a great ability to reduce
body weight without inhibiting pancreatic lipase level, or affecting bilirubin concen- tration, with positive
effect on increasing peroxisomal catalase level and HDL-cholesterol. Ebrahimzadeh Attari et al. (2015)
revealed a minor beneficial effect of ginger powder supplementation on serum glucose and a mod- erate,
significant effect on total cholesterol, as compared to the placebo. Malhotra and Singh (2003) also
Table 5. The most important benefits of ginger.

Relieves nausea Treats cold and flu Removes excess gas

Aids in proper digestion Reduces arthritis pain Stomach ulcers

Liver protection Relives asthma Prevents obesity Improves cognition Prevents cancer Relieves muscle pain

Prevents menstrual cramps Controls diabetes

Boosts heart health Prevents infection Detoxifies the body Skin care

Treats diarrhoea Increases sexual activity Improves brain function Regulates blood sugar

mentioned the effect of ginger on lowering cholesterol, and anti-hyperlipidemic agent, the role of ginger in the
treatment of nausea and vomiting (anti-emetic), ginger possesses anti-skin tumour promoting effects, and that
the mechanism of such effects may involve inhibition of tumour promoter-caused cellular, biochemical, and
molecular changes (Chemo-protective), anti-viral activity, anti-motion and anti-nauseant effects, anti-
inflamma- tory, diminishing or eliminating the symptoms of hyper- emesis gravidarum, ginger influence on
exert abortive and prophylactic effects in migraine headache without any side effects and anti-ulcerogenic,
Ginger and its con- stituent play pharmacological effects in cancer manage- ment via modulation of molecular
mechanism, and the mechanism consist of Inhibition of VEGF, Activation of Bax, Inhibition of Lypoxygenase,
Activation o P53, Inhibition of Interlukin, Inhibition of Bcl2 & Survivin, Inhi- bition of Cycloxygenase,
Inhibition of IFN-γ, Suppression of TNF & NF-kB and Activation of G0/G1 phase (Rahmani et al. 2014).
Accumulating evidence suggests that many dietary factors maybe used alone or in combination with traditional
chemotherapeutic agents to prevent or treat disease, and ginger is example of medicinal plants which is gaining
popularity amongst modern physicians (Sakr and Badawy 2011). Gagnier et al. (2006) provide an excellent
framework for the development of future trials that focus on providing satisfactory answers to issues relating to
the efficacy of Z. officinale to ameliorate different types of pain, as well as, dosing strategies, treat- ment
duration, safety, and cost effectiveness. The most important health benefits of ginger are shown in Table 5.

Pharmacological Significance

Anti-Inflammatory Effect
The original discovery of the inhibitory effects of ginger on prostaglandin biosynthesis in the
early 1970s has been repeatedly confirmed. Ginger suppresses prostaglandin synthesis by
inhibiting cyclooxygenase 1 and cyclooxygenase2.

Anti-inflammatory effect of ginger is shown below:

Gingerol, shogaol

Suppress 5-lipoxygenase or prostaglandin synthetase activity

inhibit prostaglandin and leukotriene biosynthesis as well as it inhibit synthesis of pro-

inflammatory cytokines such as IL-1, TNF-α, and IL-8

Anti-inflammation

In another syudy ,it was also observed that 6shogaol can downregulate the gene expression of
inflammatory iNOS and COX2. Inflammation due to NFκB activation is linked to various
inflammatory diseases including cancer, atherosclerosis, myocardial infarction, diabetes,
allergies , asthma, arthritis, Crohn's disease, multiple sclerosis, Alzheimer's disease, osteoporosis,
psoriasis, septic shock and AIDS. Gingerols can inhibit LPS-induced COX2 expression while
shogaol-containing extracts have no effect on COX2 6 shogaol expression .Ginger extract with
antioxidant and anti-inflammatory ingredients such as 6 Gingerols, 6 Shogoals, Zhingerol, etc.
they can reduce inflammatory mediators such as inflammatory cytokines and chemokines due to
their effects on NFκB activation, cyclooxygenase 2 reduction, and serotonin receptor inhibition.
In ancient cultures, doctors focused on herbs to promote the body’s immune system. In many
countries , ginger and its products strengthen the immune system.

Gingerol, shogaol, and other structurally-related substances in ginger inhibit prostaglandin and
leukotriene biosynthesis through suppression of 5-lipoxygenase or prostaglandin synthetase.
Additionally, they can also inhibit synthesis of pro-inflammatory cytokines such as IL-1, TNF-α,
and IL-8. In another investigation, Pan et al. showed that in macrophages,[6] shogaol can down-
regulate inflammatory iNOS and COX-2 gene expression. Indicated that rhizome hexane fraction
extract of Z. Officinale inhibited the excessive production of NO, PGE (2), TNF-alpha, and IL-
1beta. Because of potent compounds in ginger rhizome for inhibiting allergic reactions, it may be
useful for the treatment and prevention of allergic diseases. Habib et al. showed that ginger
extract can reduce the elevated expression of NFκB and TNF-α in rats with liver cancer. The
activation of NF-κB is linked to a variety of inflammatory diseases, including cancer,
atherosclerosis, myocardial infarction, diabetes, allergy, asthma, arthritis, Crohn's disease,
multiple sclerosis, Alzheimer's disease, osteoporosis, psoriasis, septic shock, and AIDS.

Anti microbial effect of ginger:

his study confirms Ojaghian et al. (2014), where ethanolic extracts of ginger (contact phase) at
10.0 g L-1 caused an 84.5% reduction in myceliogenic and carpogenic germination of Sclerotinia
sclerotiorum causing carrot rot. In this study, inhibition was more pronounced in ginger at 10.0
g L-1, although it was comparable to the commercial fungicide Mancozeb (2.0 g L-1) at 7.5 g L-
1. The antifungal activity of the extracts against C. gloeosporioides may be due to the presence
of bioactive compounds such as gingerols (in ginger), curcumin (turmeric) and alkaloids in
dukung anak (Goel et al., 2002; Ficker et al., 2003; Kim et al., 2003: Singh et al., 2007, 2008).It
is imperative to state that as a polar solvent, methanol may have extracted more polar bioactive
compounds from ginger than polar compounds from dukung anak or turmeric, which makes
ginger treatment possess strong antifungal activity against C. gloeosporioides even at a lower
concentration. .

Antioxidant Effect

Nrf2 activated 6shagaol via alkylation of cysteine residues of Kelchlike ECH-associated protein
1 (Keap1) increased glutathione Stransferase P1 (GSTP1) levels by activating gene expression
of HO1 and NQO1 (nicotinamide adenine dinucleotide phosphate (NADPH) quinone
dehydrogenase 1. Increased synthesis of glutamathecysteine ligase (GCLC) catalytic subunit
modifying glutamatocysteine ligase subunit. Potential mechanism of 6shogaol antioxidant
action .6shogoal drives translocation of Nrf2 in the nucleus and increases the expression of Nrf2
target genes by modifying Keap1 and preventing Nrf2 from proteasome degradation. Therefore ,
the level of GSH increases and the level of ROS decreases.Ginger reduces the levels of H2O2
and MDA, enhances antioxidant enzyme activity and increases glutathione in rats with
chlorpyrifos-induced oxidative damage . Theoretically, antioxidants should be
effective.However, several factors, such as health conditions, individual differences, people’s
lifestyle, other dietary factors, as well as dosage, solubility, and oral intake of antioxidants could
affect bioaccessibility and bioavailability of antioxidants, leading to low blood levels in
general ,which probably could explain why most antioxidants don't work in the real world.

The overproduction of free radicals, such as reactive oxygen species (ROS), is known to play an
important role in the development of many chronic disease. A variety of natural products have
been reported to possess antioxidant potential, such as vegetables, fruits, edible flowers,
cereals,herbal remedies and herbal teas. Many studies have shown that ginger also has high
antioxidant acivity .The antioxidant activity of ginger was assessed in vitro by ferric-reducing
antioxidant capacity, (FRAP), 2,2diphenyl1picrylidrazyl (DPPH) and 2,20 azinobis
(3ethylbenzothiazoline6sulfonic acid) (ABTS). The results revealed that dried ginger had the
highest antioxidant activity, as the number of phenolic compounds was 5.2, 1.1, and 2.4 times
higher,respectively, than fresh, sautéed , and charred ginger . The antioxidant activity of the
different types of ginger tended to be dried ginger > sautéed ginger > charred ginger > fresh
ginger. This was mainly associated with their polyphenol content. When fresh ginger was
heated, dried ginger with higher antioxidant activity was obtained because fresh ginger contains
higher moisturecontent .However , when dried ginger was further heated to make sautéed ginger
and charred ginger, the antioxidant activity decreased, as the processing could convert gingerols
to shogoal. Additionally, a fraction of the dried ginger powder abundant in polyphenols showed
high antioxidant activity based on FRAP data, oxygen radical scavenging capacity, and cellular
antioxidant activity tests .Additionally , the type of extraction solvent can have an effect on the
antioxidant activity of ginger. An ethanolic extract of ginger showed antioxidant capacity and
iron reduction capacity equivalent to trolox, and an aqueous extract of ginger showed strong free
radical scavenging and chelating capacity.In addition, ethanolic, methanolic, ethyl acetate,
hexane, and water extracts of ginger inhibited 71%, 76%, 67%, 67%, and 43%, respectively cof
the induced oxidation of lipoproteins of human low density (LDL) from Cu2+. Results of a
xanthine/xanthine oxidase system showed that an ethyl acetate extract and an aqueous extract
had higher antioxidant properties than the extract with ethanol, diethyl ether and n-butanol.
Several studies have indicated that ginger is effective in protecting against oxidative stress.
Additionally, ginger extract could reduce ROS production in human fibrosarcoma cells with
H2O2-induced oxidative stress. In heart homogenates from stressed rats ginger extract reduced
malondialdehyde (MDA) content, which was linked to lipid peroxidation.

Anticancer Effect

Several scientific reviews and meta-analyses have looked at the uses of ginger, including for
nausea and vomiting, pain management, cancer prevention, and as an anti-inflammtory. To date,
however, there is no comprehensive review describing the physiological effects and potential
uses of ginger in fitness training and sports .The sports supplement industry has grown
significantly over the past few decades, with the global market reaching an estimated $31.2
billion in 2008. Athletes and sportspeople who are considering using ginger would benefit from
considering its physiological effects, potential benefits and adverse effects. Effects in physical
training and sports. Miho Akimotos’s study demonstrated that Syussai Ginger extract (SSHE)
had potent growth inhibitory and cell death inducing activity against pancreatic cancer cells ,
including Panc1 cells.Normal cells such as HUVEC and HPAEpiC were relatively resistant to
SSHE compared to Panc1 cells.The extract has also been shown to be effective in hypoxic
conditions, which inevitably develop in all solid tumors to varying degrees and affect the
resistance of cancer cells to radiation therapy and conventional chemotherapy [43, 44]. Among
various cancers, pancreatic cancer is known for its unusually hypoxic microenvironments [45].
Our results showed that SSHE could induce Panc1 hypoxic cell death, which could be a notable
feature of SSHE for the treatment of pancreatic cancers. In addition to pancreatic cancer, SSHE
also induced marked cell growth retardation and cell death in a variety of cancer cells, which
supports the applicability of ginger extract and its active constituents for the treatment of tumors.

After treatment of Panc1 cells with SSHE, mitochondrial membrane potential was significantly
reduced and the number of annexin V-positive cells increased 24 hours after SSHE
administration. However, a small increase in subG1 phase cells, fragmented nuclei and caspase3
activation, all of which are hallmarks of apoptosis, was observed.Moreover, zVADfmk failed to
rescue SSHE-induced cell death. Since annexin V stains both primary and apoptotic necroptotic
cells [46] and mitochondrial dysfunction can also be caused by mitophagy, the autophagic
removal of mitochondria [47], we considered the possibility that the SSHE cells do not die, this
was due to apoptosis. Additionally, necroptosis was ruled out because necrostatin1 could not
ameliorate SSHE-induced cell death. We then explored the possibility of autophagic cell death
and noted numerous cytoplasmic vacuoles and LC3 puncta in SSHE-treated Panc1 cells at early
stages. SSHE treatment significantly increased the LC3II/LC3I ratio and resulted in the loss of
SQSTM1/p62.SSHE activated AMPK and inhibited mTOR. 3Methyladenine and chloroquine
partially rescued SSHE-induced cell death.

Anti-diabetic effect of Ginger:

The study was undertaken to evaluate the antidiabetic properties of an aqueous extract of ginger
in sTZ-induced diabetic rats. sTZ diabetic rats showed a significant increase in serum glucose,
cholesterol and triacylglycerol levels.The current results clearly show that an aqueous extract of
raw ginger effectively lowers serum glucose, cholesterol and triacylglycerol levels in diabetic
rats .However ,it should be noted that serum glucose levels in ginger-treated diabetic rats did not
reach normal levels at the dosage used in the present study .A similar result was reported by
Akhani et al. (2004) in their study on the effects of ginger juice in STZ-induced diabetic rats.In
addition, the current results also demonstrate that the rough ginger extract has completely
eliminated the proteiindiation caused by diabetic nephropathy (Figure 5).In contrast, in another
study, non-diabetic patients with coronary heart disease showed no decrease in blood lipid or
sugar levels when treated with a daily dose of 4 g of ginger powder for a period of 3 months
(Bordia et al. 1997). Akhani et al. to the. (2004) reported that ginger juice exhibits hypoglycemic
activity in normal and STZ-induced diabetic rats.obviously ,the results of the present study
confirm the observations of Akhani et al. (2004) related to glycemic control. No previous studies
have reported changes in kidney function following the administration of ginger.
In the present study, using a diabetic rat model, we demonstrated that an aqueous extract of raw
ginger has potential hypoglycemic properties. This hypoglycemic action of ginger may be due to
effects involving serotonin receptors, increased pancreatic insulin secretion by b cells, or related
insulin release.More work is needed to investigate how ginger lowers glucose levels in diabetic
rats. Additionally, the results also demonstrate that raw ginger can potentially reverse
nephropathy in STZ-induced diabetic rats. Since urinary albumin levels are a selective marker of
glomerular damage and high urinary albumin levels are a precursor to progressive nephropathy
(Viberti et al. 1982), future studies should focus on the effects of ginger administration on
urinary albumin levels. . It should be noted that we have previously reported that the doses of
ginger used in the present study are non-toxic in rats (Alnaqeeb et al. 2003). Therefore, it can be
concluded from these studies that raw ginger has significant potential in the treatment of
diabetes. 

Diabetes mellitus is known as a severe metabolic disorder caused by insulin deficiency and/or
insulin resistance, resulting in an abnormal increase in blood glucose. Prolonged hyperglycemia
could accelerate protein glycation and the formation of advanced glycation end products (AGEs)
[87].

Many research works have evaluated the antidiabetic effect of ginger and its major active
constituents [88].

An in vitro experiment resulted in both 6-shogaol and 6-gingerol preventing the progression of
diabetic complications, and they inhibited the production of AGEs by trapping methylglyoxal
(MGO), the precursor of AGEs [87]. Additionally, 6-gingerol reduced the levels of plasma
glucose and insulin in mice with high-fat diet-induced obesity. Nε-carboxymethyl-lysine (CML),
a marker of AGEs, was decreased by 6-gingerol through Nrf2 activation [88]. In 3T3-L1
adipocytes and C2C12 myotubes, 6-paradol and 6-shogaol promoted glucose utilization by
increasing AMPK phosphorylation. In addition, in a mouse model fed a high-fat diet, 6-paradol
significantly reduced the level of blood glucose [10]. In another study, 6-gingerol facilitated
glucose-stimulated insulin secretion and ameliorated glucose tolerance in type 2 diabetic mice by
increasing glucagon-like peptide 1 (GLP-1). Besides, 6-gingerol treatment activated glycogen
synthase 1 and increased cell membrane presentation of glucose transporter type 4 (GLUT4),
which increased glycogen storage in skeletal muscles [89]. Furthermore, the consumption of
ginger could reduce the levels of fasting plasma glucose, glycated hemoglobin A (HbA1C),
insulin, TG, and TC in patients with type 2 diabetes mellitus (DM2) [90]. Moreover, ginger
extract treatment improved insulin sensitivity in rats with metabolic syndrome, which might have
been relevant to the energy metabolism improvement induced by 6-gingerol [91]. In addition,
ginger extract alleviated retinal microvascular changes in rats that had diabetes induced by
streptozotocin. Ginger extract could reduce the levels of NF-κB, TNF-α, and vascular endothelial
growth factor in the retinal tissue [92]. In a randomized, double-blind, and placebo-controlled
trial, the ingestion of ginger decreased the levels of insulin, low-density lipoprotein cholesterol
(LDL-C), and TG; decreased the homeostasis model assessment index; and increased the
quantitative insulin sensitivity check index in patients with DM2 [93].

The studies have demonstrated that ginger and its bioactive compounds could protect against
diabetes mellitus and its complications, probably by decreasing the level of insulin, but
increasing the sensitivity of insulin.

2.8. Antiobesity Activity

Obesity is a risk factor for many chronic diseases, such as diabetes, hypertension, and
cardiovascular diseases [83]. Several studies have reported that ginger is effective in the
management and prevention of obesity [9,84].

In 3T3-L1 preadipocyte cells, gingerenone A exhibited a greater inhibitory effect on

adipogenesis and lipid accumulation than gingerols and 6-shogaol. Gingerenone A could also
modulate fatty acid metabolism via the activation of AMPK in vivo, attenuating diet-induced
obesity [9]. In cultured skeletal muscle myotubes, 6-shogaol and 6-gingerol could increase
peroxisome proliferator-activated receptor δ (PPARδ)-dependent gene expression, and this
resulted in the enhancement of cellular fatty acid catabolism [83]. In addition, both ginger and
orlistat reduced the body weight and lipid profile of high-fat diet rats, while ginger had a greater
effect on increasing the level of HDL-C than orlistat did [84]. In a randomized, double-blind, and
placebo-controlled study, obese women receiving 2 g of ginger powder daily had a decreased
body mass index (BMI) [85]. Moreover, the intake of dried ginger powder could reduce
respiratory exchange ratios and promote fat utilization by increasing fat oxidation in humans
[86].
Ginger and its bioactive constituents, including gingerenone A, 6-shogaol, and 6-gingerol, have
shown antiobesity activity, with the mechanisms mainly related to the inhibition of adipogenesis
and the enhancement of fatty acid catabolism.

Adverse Effect of Ginger

Ginger is generally recognized as safe by the food and medicine administration.However, the
evidence for ginger supplementation in humans is equivocal; several studies found no significant
effect on thromboxane production or bleeding time, while others showed significant reductions
in platelet aggregation and thromboxane production.

It remains to be determined whether ginger, like NSAIDs, affects the risk of hyponatremia and
connective and bone tissue remodeling. Human studies examining the effects of ginger on kidney
physiology and function are needed to determine if ginger is a potentially nephrotoxic agent that
should be avoided during prolonged resistance exercise. Likewise, more research is needed to
determine whether ginger supplementation alters the connective tissue and bone remodeling
process that normally occurs during exercise under load.

Finally, the effects of ginger on muscle protein synthesis and adaptations to endurance and
resistance training should be examined. It has been hypothesized that COX enzymes regulate
muscle protein synthesis and that COX inhibition may attenuate the increase in muscle protein
synthesis that normally accompanies exercise. Given ginger's inhibition of COX enzymes, it is
possible that chronic ginger consumption may alter functional and morphological responses to
resistance and resistance training.
Conclusions

In conclusion, ginger contains diverse bioactive compounds, such as gingerols, shogaols, and
paradols, and possesses multiple bioactivities, such as antioxidant, anti-inflammatory, and
antimicrobial properties. Additionally, ginger has the potential to be the ingredient for functional
foods or nutriceuticals, and ginger could be available for the management and prevention of
several diseases such as cancer, cardiovascular diseases, diabetes mellitus, obesity,
neurodegenerative diseases, nausea, emesis, and respiratory disorders. In the future, more
bioactive compounds in ginger could be isolated and clearly identified, and their biological
activities and related mechanisms of action should be further investigated. Notably, well-
designed clinical trials of ginger and its various bioactive compounds are warranted to prove its
efficacy against these diseases in human beings.