Pharmacology of Aardraka-Ginger (Zingiber officinale) Part 5
Pharmacology
of Aardraka-Ginger
(Zingiber officinale) Part 5
Some
testimonials from modern research
Pharmacokinetics of Ginger
A
study was designed to investigate pharmacokinetics of Ginger (Zingiber officinale). After oral
administration of 2.0 G of Ginger
(Zingiber officinale) extract to
human volunteers, free 10-gingerol and 6-shogaol were detected in plasma with
peak concentrations at 1 hour, but no free 6-gingerol and 8-gingerol were
detected up to 24 hours. Very low concentrations (2-3 ng/mL) of 10-gingerol
glucuronide and sulphate were found in colon tissues. Pharmacokinetic analysis
showed that half lives of [6-8-10]-gingerol and 6-shogaol and their metabolites
were 1-3 hours in human plasma. No accumulation of these phytochemicals and
their metabolites was observed both in plasma and colon tissues after multiple
daily dosing. [239]
In
a study the solubility of phytochemicals from Ginger (Zingiber officinale) was found to be low to moderate in various pH
buffers but on oral administration they were stable in gastric and intestinal
juices. The metabolic products of these phytochemicals were unstable and showed
high intrinsic clearance in mouse, rat, dog and human liver microsomes. Upon
oral administration of 250mg/kg bodyweight of Ginger (Zingiber officinale) phenolics, sub-therapeutic concentration of
the chemicals was observed. Trteament with β-glucuronidase increased the
exposure of Ginger (Zingiber officinale)
phenolics by 10 to 700 fold. [240]
For
centuries, the rhizome of Ginger (Zingiber
officinale) was used as an anti-inflammatory agent worldwide. The
phytochemicals of the plant were shown to inhibit coclooxygenase-2. This
explains anti-inflammatory activity of the plant. [241]
According to nine
clinical studies, various phytochemicals in Ginger (Zingiber officinale) are strong anti-inflammatory agents. Of these,
oleoresins are the strongest. Administered at 1-3 g per day over a period of
two to three months, Ginger (Zingiber
officinale) reduced the inflammatory marker C reactive protein (CRP) in the
blood. The phytochemicals display anti-inflammatory activity by different
mechanisms. The oleoresins show anti-inflammatory activity at cellular level.
One of the pungent components blocked Nuclear Factor-κB (NF-κB) pathway that
reduces the activity of inflammatory genes in immune cells. Some components
inhibit the release of inflammatory cytokines such as Interleukin-1 β (IL- β).
Some components block inflammation and pain causing cyclooxygenase (COX)
enzymes, thereby reducing inflammation causing chemicals, leukotrienes and
prostaglandins. [242]
Antioxidant activity of Ginger
The
rhizome of Ginger (Zingiber officinale)
contains a very high level of antioxidants 3.85 mmol/100g. Reactive nitrogen
species such as nitric oxide cause DNA damage. Ginger (Zingiber officinale) inhibits the production of nitric oxide. At a
dose 100mg/kg bodyweight Ginger (Zingiber
officinale) normalizes the nitric oxide levels. Ginger (Zingiber officinale) decreases
age-related oxidative stress. [243]
Immunomodulatory activity of Ginger
In vitro and in vivo
the volatile oil of Ginger (Zingiber
officinale) significantly inhibited T-lymphocyte proliferation, decreased
the number of the total T-lymphocytes and T-helper cells. In addition the
volatile oil of Ginger (Zingiber
officinale) inhibited interleukin-1α (IL-1 α) secretion by the peritoneal
macrophages in the mice. [244]
Lipopolysaccharides induce production of nitric oxide. Phytochemicals of Ginger (Zingiber officinale) inhibit the production of nitric oxide, significantly reduce nitric oxide expression and modulate macrophage function. [245]
Antibacterial activity of Ginger
Ginger (Zingiber officinale) showed antibacterial activity against Enterobacter spp, Serratia marscense,
Acinetobacter spp, Escherichia coli, Pseudomonas aeruginosa, Klebsiela spp,
Salmonella spp, Staphylococcus spp, Streptococcus spp and Micrococcus spp. [246]
Antiviral
Activity of Ginger
Human
respiratory syncytial virus when attaches to respiratory mucosa, causes
inflammation of respiratory tract. Hot water extract of fresh Ginger (Zingiber officinale) but not of dry
rhizome at a concentration of 300 μg/mL displays anti human respiratory syncytial virus (HRSV)
activity. The extract prevents/blocks the attachment and internalization of the
virus to respiratory mucosa. The effect is dependent on the dose employed. This
activity was attributed sesquiterpenes contained in Ginger (Zingiber officinale) extracts.
Another
study showed that the inhibition of the human respiratory syncytial virus
(HRSV) occurred more readily among the alveolar cells of the lung. Notably the
dried Ginger
(Zingiber officinale), shunthee, did
not have the same effectiveness upon the virus. This indicates that some of the
antiviral constituents of fresh ginger are lost during drying process. [247]
The human norovirus is surrogate of feline calivirus.
This is a surrogate because calivirus is a type of Norwalk virus. Norovirus
causes gastroenteritis in winter. Hence it is also known as winter vomiting
bug. In humans it causes nausea, vomiting, diarrhea, stomach pain. In a study
in 2016, researchers from the University of Minnesota showed that Ginger (Zingiber officinale) has anti-norovirus/
anti-Norwalk activity.
Researchers from Japan
found that Ginger (Zingiber officinale)
extract stimulated the production of Tumor Necrosis Factor- α (TNF- α)
expression by the human immune system. By this means Ginger (Zingiber officinale) inhibited the
replication of Influenza A virus.
Indian researchers
showed that the compound allicin found in Ginger (Zingiber officinale), by inhibiting the binding capacity of the
virus, inhibited the H1N1 Influenza A virus.
Researchers from
Heidelberg University of Germany found that essential oils from Ginger (Zingiber officinale) inhibited the
replication of Herpes Simplex Virus-2 (HSV-2) within RC-37 cells and halted the
formation of plaque by 90 percent. Further study showed that by interacting
with the viral envelope essential oils from Ginger (Zingiber officinale) inhibited the viral growth.
Researchers
found that administration of 500 milligrams of Ginger (Zingiber officinale) twice a day significantly reduced nausea and
vomiting in HIV-positive patients. Whether this was due to the antiviral
activity of the herb or due to the beneficial gastrointestinal effects of the
herb is not known. [248]
Antifungal Activity of Ginger
Recently
researchers isolated [6], [8], [10]-gingerols from Ginger (Zingiber officinale). These compounds displayed antifungal activity
against Candida albicans. [249]
Anthelmintic activity of Ginger
Administration
of extracts of Shunthee, dry powder of Ginger (Zingiber officinale) to sheep at the dose of 1-3 gram/kg body
weight eliminated gastrointestinal nematodes. The herb is also larvicidal
against Anisakis simplex. [250],
[251]
Actions of Ginger on Skin
Eczema
is also known as dermatitis. It is an inflammatory disorder. In this disorder,
inflamed, red, itchy, cracked, rough patches appear on the skin. The
phytochemical 6-Shogaol of Ginger (Zingiber
officinale) reduced eczema in mice. [252]
Topical application of [6]-gingerol
or [6]-paradol for 30 minutes prior to 12-O-tetradecanoyl-phorbol-13-acetate
attenuated the skin papillogenesis initiated by 7, 12- dimethylbenz[a]nthracene
in female ICR mice. [253]
Actions on Musculoskeletal System
One
of the features of inflammation is increased oxygenation of arachidonic acid.
It is metabolized by two pathways- the cyclooxygenase (CO) and the
5-lipoxygenase (5-LO)-leading to the production of prostaglandins and
leukotrienes respectively. They can induce inflammation in musculoskeletal
system. In a study on 28 patients with rheumatoid arthritis, 18 with
osteoarthritis and 10 with muscular discomfort, powdered Ginger (Zingiber officinale) was used for
3months to 2.5 years to treat these afflictions. Seventy five percent of the
patients with arthritis experienced pain relief, and reduced joint pains. Those
with muscular discomfort were relieved completely. None of the patients
reported adverse effects during the period of consumption of Ginger (Zingiber officinale). The ameliorative
effect could be due to inhibition of prostaglandin and leukotriene
biosynthesis. [254]
In
another study administration of Ginger (Zingiber
officinale) at a dose1g/day could reduce inflammatory markers in patients
with osteoarthritis of the knee. This suggests that Ginger (Zingiber officinale) can be recommended
as a suitable supplement for these patients. [255]
In
one study of 261 patients with osteoarthritis, a standardized Ginger (Zingiber officinale) extract was administered
for six weeks. The extract reduced the inflammation and symptoms of
osteoarthritis. The extract was found to be safe and caused only mild stomach
upset.
In
another study of 75 patients with osteoarthritis Ginger (Zingiber officinale) extract was effective only for the short-term
and the benefits were not sustained. The discrepancy could be due to the
different Ginger (Zingiber officinale)
extracts used. [256]
Actions of Ginger on Hematopoetic
system
Chang
and Whitakar reported that Ginger (Zingiber
officinale) increased bleeding time after surgery or if taken in
association with anticoagulant drugs such as warfarin. Someresearchers reported
that Ginger (Zingiber officinale) has
no effect on clotting status in healthy subjects. [258]
Actions of Ginger on Eye
A current study showed that Ginger (Zingiber officinale) extract containing
5% of 6-gingerol attenuated the retinal microvascular changes in rats with streptozotocin-induced
diabetes. The gingerol showed ant-inflammatory and antiangiogenic activity in
the experimental animals. This requires further investigation. [259]
Actions
of Ginger on Nervous System
Eight trials were
published on analgesic activity of Ginger (Zingiber
officinale). The study included 481 patients. Researchers reported
satisfactory analgesic activity in osteoarthritis, dysmenorrhea, muscular aches
and pains. This is due to the anti-inflammatory property of the constituents of
the rhizome of the plant. [260]
Various
extracts of the dried rhizome of Ginger (Zingiber
officinale), Shunthee; display Muscarinic, Ca++ antagonist and
specific butyrylcholinesterase inhibitory activity. This explains its use in
dementia. [261]
Studies
on 60 middle aged women revealed that daily intake of 400 to 800 mg of Ginger
(Zingiber officinale) extract for 2 months enhanced cognition. This was due to
the antioxidant property of the herb. [262]
Alzheimer’s disease
(AD) is a chronic, progressive, irreversible neurodegenerative disorder among
aging people. The anti-inflammatory and antioxidant properties of phenolics from Ginger (Zingiber officinale) prevent the aggregation of amyloid-β (Aβ) in
the brain. Additionally the herb displays serotonin 5 hydroxytryptamine 1A
(5HT-1A) receptor agonist activity. This also helps prevent and treat
Alzheimer’s disease (AD). [263], [264]
Actions
of Ginger on Respiratory System
Components of Ginger (Zingiber officinale) suppress allergic
reactions. This property is useful for the prevention and treatment of
bronchial asthma. Ghayur et al reported that in mouse model Ginger (Zingiber officinale) extract via calcium
channel mediated pulmonary inflammation, inhibited airway contraction.
Intraperitoneal injections of Ginger (Zingiber
officinale) extract markedly decreased eosinophil accumulation in the
lungs. The researchers feel that gingerols contained in the herb are
instrumental for these effects. [265]
Actions of Ginger on Cardiovascular
System
Administration
of Ginger (Zingiber officinale)
extract or Ginger (Zingiber officinale)
compounds showed antiplatele aggregation activity. This prevents coronary
artery disease without the side effects of aspirin. A study showed that
consumption of 5 g of Ginger (Zingiber
officinale) inhibited platelet aggregation.
Ginger
(Zingiber officinale) showed a very
mild blood pressure lowering activity. However Ginger (Zingiber officinale) and nifedipine were reported to have
synergistic effect in hypertensive patients. Ginger (Zingiber officinale) and ginger compounds have been reported to
directly stimulate myocardial sarcoplasmic reticulum calcium uptake but its
therapeutic use in treating heart failure has not been advocated. [266]
In
an experimental study, atherosclerosis was induced in rabbits by feeding
cholesterol (0.3 g/kg body weight per animal) for 75 days. The atheroma
developed in aorta and coronary arteries. Administration of Ginger (Zingiber officinale) / Shunthee at the
dose of 0.1 g/kg body weight per animal for 75 days significantly inhibited the
development of atheroma by 50%. Treatment with Shunthee significantly decreased
lipid peroxidation and enhanced fibrinolytic activity in the animals. However
Ginger (Zingiber officinale) /
Shunthee did not lower blood lipids to a significant extent. Prevention of the
development atherosclerosis by Ginger (Zingiber
officinale) / Shunthee was probably due to free radical scavenging,
prostaglandin inhibitory and fibrinolytic properties. [267]
Researchers
found that activity of Angiotensin Converting Enzyme (ACE) was high in rats fed
on high cholesterol diet. However when the animals were fed on red ginger 2%
and white ginger 4% the levels of Angiotensin Converting Enzyme (ACE) were
lowered. Furthermore the plasma levels of total cholesterol, low density
lipoprotein-cholesterol, very low density lipoprotein-cholesterol and
triglyceride decreased. The level of high density lipoprotein cholesterol
increased. [268]
Actions
of Ginger on Gastro-Intestinal System
Ginger
(Zingiber officinale) extract and
ginger compounds are very potent antiemetic agents. They are also useful for
the treatment of flatulent dyspepsia, indigestion and acid peptic disease. (For
details see above)
El-Abhar et al reported
that Ginger (Zingiber officinale)
extract alleviated the symptoms of acetic acid-induced ulcerative colitis.
[269]
The anti-inflammatory
and antioxidant activities play an important role in prevention and treatment
of gastrointestinal cancers. [270]
Actions
of Ginger on the Liver
Studies
have shown that feeding rats with a diet containing 1% Ginger (Zingiber officinale) extract for four
consecutive weeks was effective in ameliorating the hepatotoxicity induced by
ethanol.[273]
Subsequent
studies have also shown that administration of 500 mg/kg body weight of aqueous
extract of Ginger (Zingiber officinale) for two consecutive weeks was effective in
ameliorating alcohol induced hepatotoxicity. [274]
Acetaminophen
or paracetamol is one of the most commonly used analgesic and antipyretic
agent. However its injudicious use can cause hepatotoxicity (liver damage).
Studies have shown that administration of a single dose of 200 and 400 mg/kg
body weight of aqueous extract of Ginger (Zingiber
officinale) to rats before administration of paracetamol was effective in
preventing paracetamol-induced hepstotoxicity. Other studies have shown that
administration of graded doses of 100, 200 and 400 mg/kg body weight extract of
Ginger (Zingiber officinale) to rats
at 12 hour interval for 48 hours prior to administration of a single dose of
640 mg/kg body weight of paracetamol displayed hepatoprotective effect. [276]
Oral
administration of ethanolic extract of Ginge (Zingiber officinale) to rats ameliorated carbon
tetrachloride-induced hepatotoxicity. Additionally histopathological study also
showed that the extract normalized the structure of the liver. [277]
Lindane is used to
treat lice and scabies. It works by killing lice and mites. It is also known as
gammaxene, Gammallin and gamma-hexachlorocyclohexane (γ-HCH). Sometimes it is
ironically called as benzene hexachloride (BCH). It is organochlorine, an
isomer of hexachlorocyclohexane. [278]
Lindane is a potent toxin that damages the nervous
system, liver and kidneys. Studies have shown that dietary supplement of Ginger
(Zingiber
officinale) 1%w/w was effective in
reducing Lindane-induced lipid peroxidation and hepatotoxicity. This is due to
antioxidant property of Ginger (Zingiber officinale). [279]
Ethylene-bis-dithiocarbamate (Mancozeb) is a potent fungicide. It is widely used in agriculture to protect field crops, fruits and nuts. Mancozeb is a cholinesterase inhibitor and affects the nervous system. Mancozeb is hepatotoxic. Studies on albino rats have shown that Ginger (Zingiber officinale) at the concentration of 24mg/ml (dose not mentioned) three times a week for six weeks was effective in protecting the liver against mancozeb-induced liver toxicity. [280]
Bromobenzene is used in industry as a solvent. It
is used as an additive to motor oils. Exposure to bromobenzene causes
neurotoxicity and hepatotoxicity. Studies have shown that administration of
ethanolic extract of Ginger (Zingiber officinale) at 100, 200 and 300 mg/kg
body weight for two weeks, one week prior to exposure to bromobenzene prevents
hepatotoxicity or alleviates previously existing hepatotoxicity. [281]
Parabens are an important class of preservatives. They are widely used in pharmaceutical industries, for preparing shampoos, commercial moisturizers, shaving creams, tropical lubricants, tooth pastes, tanning solutions etc. Methylparaben, ethylparaben, propylparaben, butylparaben are most commonly used parabens. They are shown to induce allergic reactions hepatotoxicity. Studies on mice have shown that co administration of 3 mg/kg bodyweight of aqueous extract of Ginger (Zingiber officinale) per animal for 30 days along with parabens ameliorated paraben toxicity. [282]
Heavy
metals like lead, arsenic, zinc, cadmium, mercury etc are hepatotoxic. They are
environmental pollutants. Studies by Vitalis et al showed that feeding Ginger (Zingiber officinale)
containing diet to male Wistar rats was effective in ameliorating hepatotoxicity. [283]
Ferrous sulphate is the
commonest oral iron supplement used to treat iron deficiency anemia in humans. Iron
overload induces toxic effects in the body. In an experimental study, ferrous
sulphate was administered to rats at 30 mg/kg body weight/ day for 14 days. To
evaluate the protective role of hydroalcoholic extract of Ginger (Zingiber officinale) against ferrous
sulphate induced hepato-renal dysfunction and structural damages, the rats were
treated with Ginger extract at 400mg/kg body weight for 14 days. The results
suggest that Ginger (Zingiber officinale)
ameliorates ferrous sulphate induced toxicity.[284]
The liver cancer is
caused by chronic consumption of hepatotoxins, viruses such as hepatitis B and
C. Feeding of oleoresins from Ginger (Zingiber officinale) at 100 mg/kg body
weight to rats for eight weeks reduced the number of liver nodules. [285]
Mechanisms
of Action
By various
mechanisms Ginger (Zingiber officinale) exerts its pharmacological actions.
They can be summarized as……
1. It is a
potent anti-inflammatory agent
2. It has a
potent antioxidant and free radical scavenging property.
3. It
inhibits/breaks the chain of lipid peroxidation.
4. It enhances
enzymatic and non-enzymatic antioxidant systems in vitro and in vivo
5. It
modulates detoxifying enzymes.
Actions
on Pancreas
To evaluate the action
of aqueous extract of Ginger (Zingiber
officinale) on function and structure of pancreas, alloxan was used to
induce diabetes in rats. Diabetic rats were then treated with 500mg/kg body
weight per day and 1000mg/kg body weight per day of aqueous extract of Ginger (Zingiber officinale). The result showed
with either dose the extract was effective in lowering serum glucose to normal
levels. The microscopic study showed that the extract also restored the
pancreatic structure to normal. [286]
A group of researchers
studied the effect of ethanol extract of Ginger (Zingiber officinale) on human pancreatic cancer cell lines
including Panc-1 cells. The extract enhanced the vacuolization of the cytoplasm
in Panc-1 cells. Researchers also found that cancer cell death was due to
autosis (autophagy) and not due to apoptosis. Focal cell membrane rupture,
nuclear shrinkage, focal swelling of the perinuclear space and electron dense
mitochondria, the unique features of autosis were observed. The extract
enhanced the generation of reactive oxygen species. Additionally the antioxidant
N-acetylcystein attenuated cell death. The extract did not show adverse side
effects on normal cells. [287]
Actions
on Metabolism
To evaluate the
efficacy of lipid lowering activity of aqueous infusion of Ginger (Zingiber officinale) the infusion was
administered orally (100, 200, and 400mg/kg body weight) to
hypercholesterolaemic rats. The infusion was administered for 2-4 weeks. The
results revealed that the infusion significantly lowered all parameters in
lipid profile in hypercholesteraemic rats. The effect was comparable to that of
atorvastatin. [288]
Subclinical
hypothyroidism is associated with dyslipidaemia. Due to reduction in the number
of cell surface receptors for low density lipoprotein (LDL), the catabolism of
LDL results. Hence there is accumulation of LDL resulting in high levels of low
density lipoprotein (LDL). In subclinical hypothyroidism/ hypothyroidism,
diminished secretion of cholesterol into the bile has been demonstrated. In
hypothyroidism, though the rate of synthesis of triglycerides is normal,
reduced lipoprotein lipases activity results into hypertriglyceridaemia.
The relationship
between lipid levels and hypothyroidism remains controversial. Various
observers have obtained variable and inconsistent results. But elevated levels
of lipids and triglycerides are observed in majority of cases. [289]
In an experimental
study, by using propylthiouracil, hypothyroidism was induced in rats.
Subsequently lipid profile was studied. To evaluate the effects of Ginger (Zingiber officinale) on dyslipidemia of
hypothyroid rats, 300 mg/kg body weight of Ginger (Zingiber officinale) extract was administered to rats for 30 days.
The results showed that the extract corrected the dyslipidaemia. [290]
Peroxisome
proliferator-activited receptor β and δ are nuclear hormone receptors that
govern a variety of biological processes. They may be involved in the
development of several chronic diseases such as obesity, diabetes,
atherosclerosis and cancer. This protein has been shown to be involved in lipid
accumulation. Administration of Ginger (Zingiber
officinale) to mice fed on high fat diet enhanced fat burning. Some animals
showed weight loss. In some animals the exercise endurance improved. This
activity is mediated via PPAR δ pathway [291]
Actions
of Ginger against Diabetes
Administration of raw
Ginger (Zingiber officinale) intraperitoneally
(IP) at 500 mg/kg bodyweight daily to streptozotocin-induced diabetic rats,
lowered serum glucose, cholesterol and triglyceride levels. It decreased thirst
and excessive water intake, stabilized urine output, decreased urine protein
levels, prevented weight loss associated diabetes. This suggests that Ginger (Zingiber officinale) may be valuable in
managing effects of diabetes mellitus in humans. [292]
Actions of Ginger on Urinary
System
A study showed that treatment
with ethanol extract of Ginger (Zingiber
officinale) ameliorated carbon tetrachloride-induced nephropathy. [293]
Gentamycin (GM) is the commonest
aminoglycoside used for the treatment of urinary tract infections. However it
is nephrotoxic. In a study on Wistar rats, to one group, 200 mg/kg body weight
of Ginger (Zingiber officinale) was
administered orally to each animal for 3 days. Then Gentamycin (GM) 80 mg/kg
body weight was administered for 7 days. To another group Ginger (Zingiber officinale) was administered
orally to each animal for 3 days then ginger plus gentamycin for 7 days. To
third group gentamycin (GM) for 7 days followed by Ginger (Zingiber officinale) orally 200 mg/kg body weight for 10 days. The
results showed that in all the groups Ginger (Zingiber officinale) protected the rats from gentamycin induced
nephrotoxicity.[294]
Lead
poisoning is associated with structural and functional abnormalities of
multiple organs. A study was arranged to evaluate the effects of Ginger (Zingiber officinale) on nephrotoxicity
induced by lead poisoning. The rats with lead-nephropathy were treated with 150
mg/kg body weight of Ginger (Zingiber
officinale) extract for3 weeks. The results revealed that the Ginger (Zingiber officinale) extract ameliorated
the toxic effects lead. [295]
Actions
on Ginger on Male Reproductive System
A study on rats showed
that oral administration of 100mg/kg bodyweight per day of Ginger (Zingiber officinale) increased total
serum testosterone. Besides Ginger (Zingiber
officinale) increased the sperm count, the percentage of viable sperms and
the motility of the sperms. This suggests that Ginger (Zingiber officinale) may be used to improve fertility in subfertile
males. [296]
More than twenty years
ago, scientists have discovered the link between Ginger (Zingiber officinale) and testosterone. Recent studies showed that
of 75 infertile/ subfertile males treated with Ginger (Zingiber officinale) for three months, 17% showed increase in
testosterone levels. The treatment also increased the sperm count and motility
of the sperms. [297]
Studies reveal that
administration of 500 mg daily for three months of Ginger (Zingiber officinale) powder to infertile men protected sperm DNA
against oxidative damge. After treatment their sperm DNA quality greatly
improved. Essential oil of Ginger (Zingiber
officinale) also reduced DNA damage from aflatoxin B1 in cells. [298]
Cisplatin is an
anticancer chemotherapeutic agent. It is cytotoxic to many normal tissues also.
Its toxic effects on reproductive organs are ominous. To evaluate the
beneficial effects of Ginger (Zingiber
officinale) against cisplatin toxicity, ethanol extract of Ginger (Zingiber officinale) at the dose of
1g/kg body weight/ day was administered orally to albino rats 21 days prior to
a single intraperitoneal (IP) injection of 10 mg/kg body weight of cisplatin.
Oral administration of Ginger (Zingiber
officinale) was continued to a total of 26 day-course (21 days prior and 5
days after cisplatin). The extract protected the animals from cisplatin
toxicity. There was no testicular damage and sperm motility was restored to
normal. [299]
The term “gavage”
refers to supplying nutrition or medicines by means of a nasogastric or orogastric
tube. This route of administration is preferred for studies on experimental
animals. Sodium arsenite is toxic to male reproductive system. In a study male
rats were exposed to sodium arsenite at the dose, 10mg/kg body weight/day by
gavage via oral cannula. Weight of the reproductive organs, sperm count,
motility of the sperms; weight of the epididymis, weight of the prostate and
seminal vesicles confirmed the toxicity of male reproductive system. The
animals were then treated with aqueous extract of Ginger (Zingiber officinale) at the dose 500mg/kg body weight for 30 days.
The extract was found to protect the reproductive system from the toxicity of
sodium arsenite. [300]
Actions on Female Reproductive System
A group of researchers studied the effect of steam
distilled extract of Ginger (Zingiber
officinale) on endometrial cancer cell (ECC) lines (ECC-1) and Ishikawa
cells. At the concentration of 1.25μg/mL the steam distilled Ginger extract
(SDGE) inhibited the proliferation of ECC-1 and Ishikawa cells. SDGE also
enhanced the anti-proliferative effect of radiation and cisplatin, decreased
proliferation of ECC-1 and Ishikawa cells and induced apoptosis. Of various
phenolic compounds contained in Ginger (Zingiber
officinale), 6-gingerol was weaker than 6-shogaol in this regard. SDGE
treatment resulted in a rapid and strong increase in intracellular calcium and
20 to 40% decrease in the mitochondrial membrane potential. The researchers
concluded that terpenoids from steam distilled ginger extract (SDGE) mediated
apoptosis by activating p53. This activity should therefore be investigated as
agents for the treatment of endometrial cancer.
[301]
In an experimental
study, cultured ovarian cancer cells were treated with Ginger (Zingiber officinale). The treatment
resulted in inhibition of nuclear factor-κ-B (NF-κ-B) activation, diminution of
secretion of Vascular Endothelial Growth Factor (VEGF) and diminution of
secretion of Interleukin-8 (IL-8). Thus treatment with Ginger (Zingiber officinale) resulted in
inhibition of growth of ovarian cancer cells. [302]
Six clinical trials revealed that 750 mg to 2000 mg of
powder form of Ginger (Zingiber
officinale) i.e. Shunthee per day during first three days of menstruation
relieved symptoms of premenstrual syndrome (PMS), especially pain due to
dysmenorrhea better than mefenamic acid or ibuprofen, commonly used non
steroidal anti-inflammatory drugs (NSAIDs)
[303]
Antitumor
Activity of Ginger
A number of preclinical
investigations have shown that phytochemicals of Ginger (Zingiber officinale) possess chemopreventive and antineoplastic
effect. A number of mechanisms have been observed to be involved. Researchers
feel that the cancer preventive activity of Ginger (Zingiber officinale) is due to free radical scavenging, antioxidant
pathways, alteration of gene expressions and induction of apoptosis. They
contribute towards decrease in tumor initiation, promotion and propagation. [304]
The anticancer
properties are attributed to pungent vanillyl compounds viz. [6]-gingerol and
[6]-shogaol and other constituents zingerone etc. These compounds are
anti-inflammatory, antioxidant agents. [305]
Toxicity/
Safety Assessment
Administration for 13
weeks of ginger oil at doses of 100, 200, 500 mg/kg body weight per day to rats
of either sex did not show signs of toxicity. These doses did not reveal
changes in hematological parameters, hepatic-renal functions, no changes in
serum electrolytes. [306]
In another study, administration of 500, 1000, 2000 mg/kg body weight
for 35 days of Ginger (Zingiber
officinale) to rats was not associated with any mortalities, any
abnormalities in general conditions, behavior, growth and food and water
consumption. However in male rats, dose-related decrease in serum lactate
dehydrogenase activity was observed. Very high dose of 2000 mg/kg body weight
of Ginger (Zingiber officinale) led
to slightly reduced weight of testes. [307]
Side
Effects
While Ginger (Zingiber officinale) is safe for use as
medicine, some people can have moderate side effects such as heart burn,
gastric discomfort and diarrhea. Some women have reported extra menstrual
bleeding while taking Ginger (Zingiber
officinale).
Ginger (Zingiber officinale) is possibly safe
when applied to the skin appropriately, short term. However its long term use
may cause skin irritation for some people. [308]
Special
Precautions
Children: Ginger
(Zingiber officinale) is safe for use
in children up to 4 days and for teenage girls around the beginning of their
period.
Pregnancy:
Pregnancy
is a special event in the life of a woman. While Ginger (Zingiber officinale) is useful for the treatment of morning
sickness its use in later part of pregnancy is controversial. There is some
concern that Ginger (Zingiber officinale)
might increase the risk of bleeding during delivery. However if Ginger (Zingiber officinale) is necessary to be
used, risk against benefit must be assessed before its use.
Lactation
and breast feeding: There is not enough reliable data
regarding the use of Ginger (Zingiber
officinale) during lactation and breast feeding. It is safer to avoid its
use during lactation.
Bleeding disorders:
Taking Ginger (Zingiber officinale)
certainly increases the risk of bleeding. It must be avoided in such
conditions.
Diabetes: Ginger
(Zingiber officinale) might increase
the insulin levels and lower blood sugar levels. Those who take anti-diabetic
drugs should take precautions before using Ginger (Zingiber officinale).
Heart ailments:
Ginger (Zingiber officinale) might
worsen some heart ailments. [309]
Contraindications
There
are no specific contraindications for the use of Ginger (Zingiber officinale). With proper precautions it can safely be
used.
Traditional
and Ayurvedic uses
Gastro-Intestinal Troubles
(GIT): According to
Ayurveda and proverbial grandmothers, Ginger (Zingiber officinale) is a remedy par excellence for nausea,
vomiting, dyspepsia and indigestion. It was indeed the drug of choice used by
pregnant women for morning sickness. In this condition its action is slow and
the dose to be used may be a little larger. Traditionally a combination of
Ginger (Zingiber officinale) and
lemon juice is used to treat Gastro-Intestinal troubles (GIT).
Jaundice:
Ginger (Zingiber officinale) was an important
drug used for jaundice. Here it was used in combination with lemon juice or
with jaggery to make it more
palatable or agreeable.
Dizziness,
Fainting, Vertigo etc: This group of symptoms has a wide
range of etiology. Whatever the cause be Ginger (Zingiber officinale) does relieve these symptoms.
Respiratory disorders: While
episodic cough is troublesome to the patient, the incessant cough disturbs
others around him. Ginger (Zingiber
officinale) powder or aqueous extract does relieve cough.
Whether
Ginger (Zingiber officinale) relieves
bronchial asthma is a subject for debate.
Arthritis:
Joint
pain of any kind is annoying, troublesome. Be it due to traumatic arthritis,
rheumatoid arthritis or osteoarthritis the sufferer becomes restless, for
he/she cannot endure the pain and does not find certain cure for the malady.
The analgesic property of Ginger (Zingiber
officinale) can alleviate the joint pain to some extent.
Dysmenorrhea:
Painful
menstruation is the worst insult inflicted on womanhood, especially at menarche
and few years of young age. Taking Ginger (Zingiber
officinale) powder 500 to 2000 mg during the first 3-4 days of menstrual
cycle can offer relief from dysmenorrheal.
Additional
information:
Ginger
(Zingiber officinale) can possibly be
used in following conditions though there is insufficient evidence. In some
conditions its efficacy is also debated.
1.
Nausea, vomiting following chemotherapy for cancer. Taking Ginger (Zingiber officinale) with chemotherapy
does not seem to prevent nausea and vomiting, but taking Ginger (Zingiber officinale) two days prior to
chemotherapy alleviate this adverse effect. This effect of Ginger (Zingiber officinale) in alleviating
nausea and vomiting are conflicting. It possible that Ginger (Zingiber officinale) helps to reduce
nausea and vomiting caused by certain drugs and not caused by others.
2.
Loss of appetite, stomach upset is a common complaint. In many patients no
satisfactory cause can be found. Taking a single dose of 1.2 grams of Shunthee
i. e. dry Ginger (Zingiber officinale)
powder one hour before food intake improves this condition.
3.
Taking Ginger (Zingiber officinale)
alone does not seem to improve symptoms of Irritable Bowel Syndrome (IBS),
Inflammatory Bowel Disease (IBD). But some polyherbal formulations containing
Ginger (Zingiber officinale) seem to
alleviate the symptoms of the patients suffering from these conditions.
Probably the synergy of the ingredients is beneficial.
4.
Many drugs especially antitubercular
drugs are hepatotoxic and cause hepatic dysfunction. Taking Ginger (Zingiber officinale) along with these drugs
might help prevent hepatic damage in some people.
5.
Taking Ginger (Zingiber officinale)
before consumption of alcohol decreases the symptoms of alcohol hangover
including alcohol-induced nausea, vomiting and diarrhea.
6. Taking two capsules of specific combination
product AKL1, AKL containing Ginger (Zingiber
officinale) twice daily for eight weeks does not improve respiratory
symptoms in patients with Chronic Obstructive Pulmonary Disease (COPD)
7.
Administration of 120 mg of Ginger (Zingiber
officinale) extract daily for up to 21 days, improves the respiratory
comfort in patients with respiratory failure. They may not require respiratory
support on ventilator. However Ginger (Zingiber
officinale) extract does not affect the death rates in people with this
condition.
8.
Drinking black tea with small quantity of Ginger (Zingiber officinale) might be useful in reducing blood pressure in
some people with hypertension. This activity is through blockade of voltage
dependent calcium channel.
9.
Taking at least 3 grams of Ginger (Zingiber
officinale) per day lowers increased blood sugar. However it might take 2-3
months before benefits are seen. Lower dose is not effective in lowering blood
sugar.
10.
Taking 1 gram of Ginger (Zingiber
officinale) three times daily for 45 days lowers cholesterol in persons
with high cholesterol levels. This dose also lowers triglycerides.
11.
Taking Ginger (Zingiber officinale)
alone helps obese people lose weight a little bit. But there may not be much
discernible effect. There is no added advantage of taking polyherbal
formulations with Ginger (Zingiber
officinale) as one of the ingredients.
12.
Ginger (Zingiber officinale) is said
to reduce the intensity of pain in migraine. It might also reduce the length of
migraine pain. [310]
Interactions
Ginger
(Zingiber officinale) might slow
blood clotting. Hence it can interact with anticoagulants, antiplatelet agents
like heparin, warfarin, aspirin, clopidogrel, phenprocoumon (a long acting
anticoagulant available outside the US). Ginger (Zingiber officinale) can interact with nonsteroidal
anti-inflammatory agents (NSAIDs) like ibuprofen, diclofenac, naproxen
etc.
Ginger
(Zingiber officinale) might lower blood
sugar. As hypoglycemic agents lower blood sugar, Ginger (Zingiber officinale) can exert summation effect with them or might
even potentiate the actions of hypoglycemic agents.
Ginger
(Zingiber officinale) might lower
blood pressure. This action is similar to calcium channel blockers. Hence
Ginger (Zingiber officinale) should
be used with caution if a patient is taking calcium channel blockers.
Ginger
(Zingiber officinale) is known to
lower cholesterol and triglycerides. Hence the dose of lipid lowering agents
should be adjusted carefully. [311]
Preparations and doses
Usually
fresh ginger or ginger powder (Shunthee) is used in the doses from 500 mg to 3
grams as a single dose or in aliquots; three or four times a day.
The
following doses and routes of administration have been documented by
researchers.
Oral Route:
For nausea and vomiting: 1
gram of fresh ginger or powder (Shunthee) daily in two divided doses 30 minutes
before each meal for 14 days.
For Dysmenorrhea, PCOD: 250
to 500 mg of ginger extract three to four times a day for first three days from
the start of the menstrual period.
Also
500 mg ginger powder three times a day, for three days starting from two days
before menstruation and continuing for three days of the menstrual cycle.
For morning sickness: 500
mg of fresh ginger two to three times a day up to three weeks as required.
For Osteoarthritis: 250
mg of extract or 250 mg of ginger powder two to three a day.
Some special
formulations-----
Eurovita
Extract 33, EV ext-33: 170 mg three times a day.
Eurovita
Extract 77, EV ext-77 which combines ginger with alpinia: 225 mg twice daily.
Zintona
EC (ginger extract): 250 mg four times a day.
Eurovita
Extract 35, EV ext-35 (Ginger extract): 340 mg daily in combination with 1000
mg of glucosamine daily for four weeks.
For nausea and vomiting after
surgery: 1 to2 grams of ginger powder after surgery.
For Vertigo: 1
gram of ginger powder as a single dose one hour before expected or suspected
attack.
Inhaled as Aroma therapy:
A
solution of ginger essential oil has been used. In aroma therapy ginger alone
or in combination with spearmint, peppermint and cardamom is used. It is
inhaled through nose and exhaled through mouth.
Application to skin:
For
osteoarthritis, a specific gel containing ginger and plai, (Plygersic gel
recommended by Thailand Institute of Scientific and Technological Research) 1
gram four times a day for six weeks [312]
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