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Antiemetic 1
Antiemetic 1
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Abstract
Chemotherapy- and radiotherapy-induced nausea and vomiting are the most common, intractable and unpleasant side effects
in patients undergoing treatment for cancer. 5-Hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone
have significantly improved the control of acute nausea and vomiting, but delayed nausea and vomiting remains a significant
clinical problem. Combined neurokinin-1 receptor antagonists with 5-HT3 antagonists and steroids are observed to be
better in the control of both acute and delayed emesis. However, the use of these antiemetics is observed to possess
inherent side effects. The medicinal plants such as Scutellaria baicalensis, Korean red ginseng, American ginseng berry,
Ganoderma lucidum, Zingiber officinale, grape seed extract, and the oil of Mentha spicata are reported to be effective in the
treatment of nausea and vomiting mostly in preclinical studies. Of these, ginger has also been evaluated for its efficacy in
humans and the results have been contradictory. The current review for the first time summarizes the results related to
these properties. An attempt is also made to address the lacunae in these published studies and to emphasize aspects that
need further investigations for these plants to be of use in clinics in the future.
Keywords
chemotherapy, radiotherapy, nausea, vomiting, medicinal plants, anti-emetic
administered, the treatment schedule, the use of combinations mediated through the autonomic nervous system, whereas
of chemotherapeutic agents, and patients’ inherent charac- vomiting results from the stimulation of a complex reflex
teristics. Chemotherapeutic agents such as carmustine, that is coordinated by a putative true vomiting center.4,10
cisplatin, cyclophosphamide (≥1500 mg2), dacarbazine, The vomiting center is believed to receive convergent
mechlorethamine, and streptozocin are the highly afferent stimuli from several central neurologic pathways.
emetogenic and cause increased frequency of nausea and The sensory stimuli of smell, taste, psychological response,
vomiting.5 and pain, led from the limbic system stimulate the chemore-
Comparatively, RINV is not as prevalent or severe as ceptor trigger zone (CTZ). Motion sickness occurs via
CINV but can interrupt treatment schedule, can negatively impulses from the labyrinthine apparatus of the inner ear.
influence the efficacy of the treatment, and can affect the Exogenous chemicals and endogenous substances that
quality of life.6 The pathophysiology of RINV is incom- accumulate during inflammation, ischemia, and irritation
pletely understood but is thought to be similar to that caused stimulate vagal and spinal nerves from visceral and vascu-
by chemotherapy.6 Unlike chemotherapy, which is systemic lature to cause vomiting and nausea.4,10
treatment; radiotherapy is delivered from an external source The cause of CINV has both components, that is, periph-
and is localized.6 The severity of RINV depends on the site eral and central, which makes it difficult to treat. Serotonin
of irradiation, the field size, and the dose per fraction.6,7 is produced by the enterochromaffin cells in the enteric ner-
RINV is very high when the total body, proper abdominal, vous system, which accounts for 80% of the total body sero-
and gastrointestinal regions are irradiated; moderate when tonin. Intestinal irritation or damage to the neoplasm leads
the upper abdomen, pelvic, and cranial parts are involved; to release of 5HT that stimulates the 5HT3 receptors and
low when the lower thorax and craniospinal regions are CTZ that ultimately stimulates the vomiting.4,10
subjected; and minimal when breast and extremities are The central pathway, on the other hand, is induced by sub-
irradiated.6,7 stance P, which is abundantly present in the CTZ and stimu-
Increased risk of CINV and RINV are observed in lates the neurokinin-1 receptors as well as the gastrointestinal
patients younger than 50 years, with history of light alcohol vagal afferent nerve fiber. A multitude of receptors is effected
use, and with history of vomiting during pregnancy-induced in CINV, namely, CB1 (canabinoid-1), D3 (dopamine-3), D2
nausea/vomiting. Additionally, patients who are dehy- (dopamine-2), H1 (histamine-1), M3, M5 (muscarinic-3 and -5),
drated, debilitated, those who have an electrolyte imbal- and GABAB (gamma amino butyric acid-B). This is reflected
ance, or those who have recently undergone surgery or in the wide array of antiemetic drugs that are present. There
radiation therapy, are also at greater risk of experiencing are more neurotransmitters and receptor systems in play
serious complications from CINV and RINV.1-3,5-7 which are as yet unascertained. In CINV sometimes although
emesis is brought under control with drugs, nausea continues
unabated, reducing the quality of life.4,10
Physiological and Biochemical
Basis for Nausea
Chronic nausea in the setting of cancer treatment is often Conventional Antiemetic Agents
multifactorial in origin. Factors such as raised intracranial Used in Cancer Treatment
pressure, metabolic abnormalities such as hypercalcemia, Antiemetic agents are the most commonly used interven-
hyponatremia, and uremia, dehydration, malignant bowel tional agents in the management of treatment-related nau-
obstruction, and gastroduodenal ulcers contribute to vomit- sea and vomiting. Conventionally, an antiemetic agent
ing and nausea.8 Nausea also has a psychological basis, should be effective against the nausea and vomiting pro-
which may either exacerbate or induce chronic nausea.8 duced by most chemotherapeutic drugs; have no interaction
Neurophysiologic studies have shown that both nausea and with the cancer chemotherapeutic agents; be available as
vomiting are controlled and mediated by the central ner- oral, injectable, and suppository forms; possess minimal
vous system but by different mechanisms.4,9 Nausea is side effects, especially euphoric reactions; be efficient and
20 Integrative Cancer Therapies 11(1)
reproducible gastrointestinal absorption; have therapeutic the cannabinoids dronabinol, nabilone, marinol, and can-
blood levels for 4 to 12 hours postadministration; be effec- nabis from Cannabis sativa commonly known as marijuana
tive with repeated use; show low abuse potential; and have is the best example.4 Scientific studies carried out in the
reasonable cost.4 past 2 decades have shown that some of the most important
The basis for antiemetic therapy is the neurochemical medicinal plants, for xample, Scutellaria baicalensis,
control of vomiting. Many antiemetics act by competitively Korean red ginseng, American ginseng berry, Ganoderma
blocking receptors for these substances, thereby inhibiting lucidum, Zingiber officinale, and grape seed extract possess
stimulation of peripheral nerves at the CTZ, and perhaps at antiemetic action against CINV and mint oil and ginger
the “vomiting center.” Combination of antiemetic regimens against RINV. In the following sections, the antiemetic and
has become the standard care for the control of CINV.10 antinausea observations are addressed.
However, the choice is complicated as when selecting an
antiemetic the clinicians must opt for an agent that provides
optimal protection against nausea and vomiting while Ginseng
avoiding drug–drug (antiemetic–anticancer) interactions Among all medicinal plants, globally, ginseng is probably
and additional adverse events. The other factors that need to the most famous and extensively investigated plant. The
be considered are the dose of antineoplastic agent used, the generic name Panax derived from the Greek word Panakos
combination of antineoplastic drugs, route of administra- means a panacea, a virtue ascribed to it by the Chinese, who
tion, and the treatment schedule.1,4 consider it a sovereign remedy in almost all diseases.12
Regimens to prevent radiation- and chemotherapy- Ginseng is a slow-growing perennial plant and the fleshy
induced nausea and vomiting are guided by the emetogenic root bears resemblance to the human body. Because of
potential of the drug dose and the combinatorial agents this morphological feature, they are also known as “man-
used. Patients in a hospital setup receiving highly emeto- root.”13,14 There are 11 species of ginseng, but the most
genic potential chemotherapy, may require higher doses of important and the well-studied species are the Panax gin-
antiemetics, whereas those receiving highly emetogenic seng (Asian, Korean, or Chinese ginseng) and Panax
chemotherapy on an outpatient basis may do best with sub- quinquefolius (also called American, Canadian, or North
lingual or rectal antiemetic routes of delivery.1,4 Various American ginseng).14,15 In the United States, where the
classes of antiemetics, their applications, and inherent side market for medicinal botanicals is US$3 billion (CA$4.3
effects are summarized in Tables 2 and 3. billion) and growing, ginseng is the top-selling herb among
first-time herbal users and ranks third, surpassed only by
Echinacea and garlic.16
Plants as Antiemetic Agents In the traditional Chinese system of medicine, ginseng is
Complementary therapies are widely used throughout the referred to as the ultimate tonic to benefit the whole body
world and according to a recent report almost 80% of the and has been used for more than 2000 years.15 Ginseng has
global population relies on alternative therapies for their been used to improve the body’s resistance to stress, to
health care.11 When compared with the conventionally used increase vitality, increase general well-being, immune func-
drugs of modern medicine, these medications are clearly tion, libido, and athletic performance. Preclinical studies
underresearched. However, their wide acceptance makes it suggest it to possess adaptogenic, anti-inflammatory, anti-
imperative that scientific investigations are performed with neurological, hypoglycemic, antineoplastic, immunomodu-
the plants commonly used in the various traditional systems latory, cardiovascular, central nervous system, endocrine,
of medicine and have been practiced for centuries.11 and ergogenic effects.14 In traditional medicine, ginseng is
Observations suggest that traditional knowledge and plants also used for the alleviation of emesis.15 Preclinical studies
have contributed to the development of antiemetic drugs in have shown that the Korean red ginseng (P ginseng)17 and
the prevention of CINV and RINV and the development of the American ginseng berry (P quinquefolius)18 prevent
Haniadka et al. 21
Table 3. Side Effects of Antiemetics Commonly Used in the Prevention of CINV and RINV
cisplatin-induced nausea and vomiting in experimental ani- 6 years old, steamed, and dried).19 Red ginseng is not skinned
mals. The following section addresses these aspects. before it is steamed or otherwise heated and subsequently
dried.19 In the course of the steaming process, ginseng starch
is gelatinized, causing an increase in saponin content.
Korean Red Ginseng in the Traditionally, red ginseng has been used to restore and enhance
Prevention of CINV normal well-being, and it is often referred to as an adaptogenic.19
In Korea, depending on the type of processing, ginseng is clas- Kim et al17 evaluated the antiemetic effect of Korean red
sified into fresh ginseng (<4 years old), white ginseng (4-6 years ginseng total extract (aqueous) on cisplatin-induced nausea and
old and dried after peeling), and red ginseng (harvested when vomiting using ferrets. In the cisplatin control, intraperitoneal
22 Integrative Cancer Therapies 11(1)
(i.p.) administration of cisplatin (7.5 mg/kg) induced both of ginsenoside might have an antagonistic action against
nausea and vomiting. After a latency period of 1 hour, the 5-HT3A receptor related to nausea and vomiting.23
episodes of nausea and vomiting initiated and reached a The observation that 100 mg/kg completely reversed
peak at 1.5 hours and persisted for 3 hours. Oral administra- pica and significantly improved food intake suggests the
tion of the extract (0.3, 1.0, and 3.0 g/kg) reduced the cispl- effectiveness of ginseng berry extracts in treating cisplatin-
atin-induced nausea and vomiting in a concentration-dependent induced nausea and vomiting. The extract possess free radi-
manner. With increase in the dose of cisplatin to 10 mg/kg, cal scavenging and antagonistic action against 5-HT3A
the nausea and vomiting were severe and the lower 2 doses receptor suggest its possible use in the prevention of CINV.
of 0.3 and 1.0 g/kg were ineffective, whereas the highest Detailed studies with other emetogenic antineoplastic drugs
dose of 3.0 g/kg exhibited significant antiemetic effects. In and also with other animal models of studies are required to
the time-dependent effect studies, the authors also observed confirm its efficacy before initiating clinical studies.
that oral administration of 3.0 g/kg of the extract was effec-
tive only when administered 1 and 2 hours before cisplatin
(7.5 mg/kg, i.p.) and that a further increase to 4 hours before Scutellaria baicalensis Georgi
cisplatin administration was not as effective as the other 2 in the Prevention of CINV
earlier time points.17 Commonly known as Baikal skullcap, Scutellaria baicalen-
sis is a perennial herb of the family Lamiaceae with fleshy
root, branched stems, papery leaves, purple-red to blue
American Ginseng Berry in flowers, and black-brown ovoid nutlets.24-27 For more than
the Prevention of CINV 2000 years, it has been one of the most widely used herbs
Studies have shown that pretreatment with ginseng berry in the traditional Chinese herbal system of medicine.24 Its
extracts (50, 100, and 150 mg/kg body weight) and the use was first documented in the Shen Nong Ben Cao Jing
phytochemical ginsenoside (2 and 5 mg/kg body weight) by circa 100 bc, and it is currently listed in the Chinese
intraperitoneal route 30 minutes before cisplatin (3 mg/kg Pharmacopoeia as one of most important herbs.25-27
body weight) resulted in a significant reduction in cisplatin- The roots are of use in the treatment of dysentery, diar-
induced pica (Pica means eating of nonnutritive substances rhea, allergic and inflammatory diseases, allergic rhinitis, to
such as kaolin, a illness-response behavior in mice20 and reduce cholesterol level, decrease blood pressures, athero-
rats.21) The phytochemical ginsenoside Re also caused a sclerosis, hypertension, cholecystitis, hepatitis, cataract, dia-
significant reduction in the intake of kaolin and the optimal betes complications, acute bronchitis, asthma, cold, cancer,
protective effect was observed at 5 mg/kg.18 bacterial and viral infections of the respiratory and the gas-
The extract also decreased the amount of kaolin con- trointestinal tract, hepatitis, jaundice, tumor, and leukemia
sumption at all time points (24, 48, 72, 96, and 120 hours) in the traditional Chinese medicine.26,28,29
with differing levels of efficacy. The lowest dose of 50 mg/ With regard to inhibition of CINV, Aung et al30 studied
kg significantly attenuated the pica but did not improve the the antiemetic effects of hot water–soluble extract of the
food intake, whereas the next higher dose of 100 mg/kg was roots of S baicalensis against cisplatin-induced alterations
effective in eliminating pica at 24 to 120 hours time point in rats. When compared with the control animals, adminis-
and also improved the food intake. With further increase in tration of cisplatin (3 mg/kg) decreased the food intake at
the dose to 150 mg/kg, pica was attenuated, especially when all study time points (1, 2, 3 and 4 days post–cisplatin treat-
compared with the cisplatin alone cohorts at both 24 and 48 ment) with the nadir being observed at 24 hours posttreat-
hours but showed a prolonged reduction in food intake from ment. A progressive recovery in food consumption was
24 to 96 hours.18 observed from day 3 onward suggesting recovery. Cisplatin
The extract was observed to be effective in scavenging treatment also increased the intake of kaolin at all the time
superoxide anion and hydroxyl radicals in vitro, thereby points, suggesting that the prolonged increase in pica con-
contributing to the protective effects at least in part.18,22 In sumption corresponds to a prolonged and delayed emetic
vitro studies with the recombinant 5-hydroxytryptamine-3A response to cisplatin in humans.31
(5-HT3A) receptor expressing xenopus oocyte have shown Pretreatment with water-soluble extract of S baicalensis
that the ginseng saponins (total saponin, panaxadiol sapo- 30 minutes before cisplatin administration caused a decrease
nin fraction, panaxatriol saponin fraction, and ginsenoside- in the intake of pica at the 2 lower doses of 1 and 3 mg/kg.
Rb1 and -Rg1) inhibit the peak current induced by the At a higher dose of 10 mg/kg the kaolin consumption
agonist 5-HT on the 5-HT3A receptor in a dose-dependent, increased, suggesting a possible pro-oxidant effect.
reversible, and voltage-independent manner. Of all the frac- However, there was no significant improvement in the food
tions, optimal results were observed with the panaxatriol intake. The authors proposed that the observed beneficial
saponin fraction, suggesting that some of the specific types effects may be because of the antioxidant effects of S
Haniadka et al. 23
baicalensis and its binding to 5-HT1A receptors.30,32 Similar adverse effects, such as restlessness or respiratory distress
results were also observed in another study and the reported following the injections. Together, these observations sug-
in vitro free radical scavenging effects of the extract con- gest that in addition to reducing the nausea and vomiting,
firmed that the antioxidant action of the herb may be, at the extract also has a supportive effect in improving the
least in part, responsible for attenuating the cisplatin- general health and appetite in animals.37
induced nausea and vomiting.22
Grape Seed Polyphenols in
Ganoderma lucidum (Fr.) Karst in the the Prevention of CINV
Prevention of CINV For thousands of years, the fruit and the plant Vitis vinifera,
Commonly known as Reishi mushroom, this white rot commonly referred to as grapes have been grown and har-
lamellaless macrofungus belonging to the phylum vested for medicinal, nutritional, and economic value. The
Basidiomycetes and family Polyporaceae is an important seeds of grapes have been a waste product of the winery
mushroom in the herbal system of medicine in China, and grape juice industry, but recent studies suggest that
Japan, and other East Asian countries.33,34 It is found to they possess immense health benefits.38,39 Depending on
grow on the dried trunks of dead plum, Guercus serrata or the variety of grapes, the seeds are reported to contain lip-
pasonia trees in densely wooded mountains where humidity ids, proteins, carbohydrates, and 5% to 8% polyphenols.
is high and the lighting is dim.35 The Chinese name of this The polyphenols in grape seeds are mainly flavonoids,
mushroom is Lingzhi, which means “spiritual potency.”33,34 including gallic acid, the monomeric flavan-3-ols catechin,
This mushroom was also regarded by the Chinese as the epicatechin, gallocatechin, epigallocatechin, and epicate-
“Medicine of Kings” and “mushroom of immortality” chin 3-O-gallate, and procyanidin dimers, trimers, and
for more than 2000 years.33-35 Phytochemical studies have more highly polymerized procyanidins.38
shown that the basidiocarp, mycelia, and spores of Reishi Scientific studies have shown that grape seed extract is a
contain triterpenoids, polysaccharides, nucleotides, powerful antioxidant and its effect is 20 times greater than
sterols, steroids, fatty acids, proteins/peptides, and trace vitamin E and 50 times greater than vitamin C,39 and it also
elements.33,36 protects the body from premature aging and various dis-
In traditional Chinese system of medicine, Reishi mush- eases.38 Studies also indicate that because of its antioxidant
room has long been used as a medicine to treat various effect, it is useful in promoting youthful skin, good cell
human diseases.36 These mushrooms are supposed to health, elasticity, and flexibility. Animal studies have also
enhance intellectual capacity and memory, promoting agility, shown that grape seed extract possess cardioprotective,
increase life span, inhibit tumor growth, reduce hyperten- anticancer, and anti-inflammation properties.39 Proantho
sion, modulate immune response, and increase hematopoi- cyanidins are also reported to protect the body from sun
etic activity.33-36 Pharmacological studies have shown that damage, to improve vision, to improve flexibility in joints,
the Reishi mushrooms possess immunomodulatory, anti- arteries, and body tissues such as the heart, and to improve
atherosclerotic, anti-inflammatory, analgesic, chemopre- blood circulation by strengthening capillaries, arteries,
ventive, antitumor, chemo- and radioprotective, sleep and veins.38
promoting, antibacterial, antiviral (including anti-HIV), With regard to prevention of CINV, Wang et al40 investi-
hypolipidemic, anti-fibrotic, hepatoprotective, anti-diabetic, gated the antiemetic effects of 3 grape seed extracts pre-
anti-androgenic, anti-angiogenic, anti-herpetic, anti-oxidative, pared in the investigators’ laboratory, obtained from a
and radical-scavenging, anti-aging, hypoglycemic, estrogenic, US-based dietary supplement company and from China.
and anti-ulcer properties.33-36 Phytochemical studies showed a great variation in the con-
Experimental studies have shown that intraperitoneal stituents of the 5 major constituents (gallic acid, catechin,
administration of 1, 3, and 10 mg/kg G lucidum extract was epicatechin, procyanidin B2, and epicatechin gallate). The
effective in attenuating cisplatin-induced nausea and vomit- extract obtained from China had the highest level of poly-
ing in the rat pica model. Additionally, the area under the phenols (194.21 mg/g), followed by the US-based dietary
curve for kaolin intake from time 0 to 72 hours for cisplatin supplement company sample level (35.84 mg/g). The low-
only, 1, 3, and 10 mg of the extracts along with cisplatin est total polyphenol content (27.27 mg/g) was observed in
treatment was 327.6, 264.0, 169.2, and 88.8 g/h, respec- the sample prepared in the investigators’ laboratory.40
tively. The reduction in the area under the curves of kaolin Pretreatment with the grape seed extract (3 mg/kg), by
intake after 1, 3, and 10 mg/kg G lucidum extract adminis- intraperitoneal route reduced the cisplatin-induced pica
trations were 19.4%, 48.4%, and 72.9%, respectively. from 0 to 72 hours but did not alter food intake or body
Additionally, when compared with the cisplatin alone weight. Conversely, with increase in the concentration to
cohorts, administering G lucidum extract was observed to 10 mg/kg, all 3 extracts decreased the cisplatin-induced
be effective in increasing the intake of food and lacked pica and with 30 mg/kg, the antiemetic effect of all the
24 Integrative Cancer Therapies 11(1)
extracts was further reduced. Among the 3 samples studied, and thus can neutralize the injurious effects of biogenic
the investigators’ laboratory sample reduced emesis by 45%, amines such as histamines and 5-HT and also modulate
the US-based dietary supplement company extract by 54%, vagal activity and reduce intestinal motility and contractil-
and the extract obtained from China by 66%, clearly indi- ity.46 Mint oil is also known to exert neurobehavioral effects,
cating that effect was proportional to the content of poly- increase alertness, sharpen mental process, and rejuvenate a
phenol in the extract. Additionally, the area under the curve sluggish and tired mind.47 All these properties may have
for kaolin intake from time 0 to 72 hours for cisplatin only, contributed to the observed effect.
laboratory sample, US company sample, and Chinese
company samples were 518.0, 284.0, 238.2, and 178.7 g/h,
respectively.40 Ginger in the Prevention of CINV and RINV
The rhizome of Zingiber officinale (family Zingiberaceae),
commonly known as ginger, is an important herb in the
Mint Oil in the Prevention of RINV various traditional systems of medicine.48 It is an integral
Mint is a broad term given for a group of aromatic perennial part of several medicinal formulations in Ayurveda, the
herbs belonging to the genus Mentha and the family traditional system of Indian medicine. In various tradi-
Labiatae. It is one of the most important culinary and medic- tional systems of medicine, ginger is reported to be a car-
inal plants in the world. In various traditional medicines, minative, diaphoretic, antispasmodic, peripheral circulatory
mint is used as a stomachic, tonic, carminative, antispas- stimulant, astringent, appetite stimulant, anti-inflammatory
modic, and anthelmintic.41 Mint oil extracted from the stem, agent in addition to being useful in treating cold, head-
leaves, and flowers of the plant by steam distillation is used aches, arthritis, rheumatological conditions, and muscular
all over the world for flavoring, cosmetic, and medicinal discomfort.48-50
purposes.41,42 The oil is traditionally used in relieving diges- Studies have shown that ginger possesses antimicrobial,
tive ailments, for irritable bowel syndrome, headache, non- antischistosomal, anti-inflammatory, antipyretic, antioxida-
ulcer dyspepsia such as indigestion, gas problem, and acidity.43 tive, hypoglycemic hepatoprotective, diuretic, and hypo-
It is also a main ingredient for Ayurvedic medicines (eg, cholesterolemic effects.49,50 Ginger is also beneficial to the
Dabur’s “Pudin Hara” used for gastric disturbances.43 gastrointestinal tract, to increase bile secretion, and to pre-
Scientific studies have shown that the mint oil possesses vent gastric ulcers.49,50 Scientific studies have also shown
analgesic, anti-inflammatory, antiseptic, anti-infectious, anti- that ginger prevents nausea and/or emesis resulting from
microbial, antispasmodic, astringent, carminative, digestive, pregnancy, motion sickness, postoperation chemotherapy,
expectorant, febrifuge, fungicidal, nervine, vasoconstrictor, and radiation, thereby validating the traditional observa-
decongestant, stimulant, cognitive enhancer, stomachic tions and emphasizing its broad-spectrum antiemetic
properties and is also effective against irritable bowel syn- effects.49,50 In the United States, ginger is recommended to
drome.41-43 At the biochemical level, mint oil is reported to relieve and prevent nausea.48
modulate calcium channel–dependent processes in intesti- Preclinical studies have shown that ginger possesses
nal, neuronal, and cardiac preparations.41-43 The oil is also antiemetic effects and prevents gastric emptying against the
reported to possess neuromodulatory and performance- highly emetogenic cisplatin. Sharma et al51 evaluated the
enhancing properties.44 anitemetice effects of various ginger extracts (acetone, 50%
Studies have shown that mint oil (Mentha spicata Linn.) ethanolic and aqueous) against emesis induced by 3 mg/kg
was effective in mitigating radiation-induced conditioned cisplatin in the healthy mongrel dogs with the 5-HT3 recep-
taste aversion (CTA), a phenomenon understood to be con- tor antagonist granisetron as a known control. The authors
trolled in rodents by the same pathways that control nausea observed that the acetone and 50% ethanolic extract at the
and vomiting in humans.45 It was observed that the intra- doses of 25, 50, 100, and 200 mg/kg per os (p.o.). exhibited
peritoneal administration of mint oil (5, 7.5, 10, 12.5, and significant protection whereas aqueous extract at these
15% v/v) 1 hour before exposure to 2 Gy of whole body doses was ineffective against emesis. The acetone extract
irradiation showed significant decrease in CTA at all doses, was more effective than ethanolic extract but was less effec-
when compared with the 2 Gy radiation control at all time tive than granisetron.51
points (1, 2, 3, 4, and 5 days post irradiation). However, the The acetone and 50% ethanolic extract of ginger in the
best effect was observed as follows 10% > 12.5% > 15% > doses of 100, 200, and 500 mg/kg (p.o.) and fresh ginger
7.5% > 5%.45 juice (2 and 4 mL/kg) were also investigated against cispla-
Mechanistically, it is quite possible that the free radical tin effect on gastric emptying in rats. It was observed that
scavenging and the antioxidant effects of mint may have all the 3 ginger preparations reversed the cisplatin-induced
contributed to the reduction in CTA. Studies have also delay in gastric emptying, and the ginger juice and acetone
shown that rotundifolone, an active constituent of mint oil, extract were more effective than the 50% ethanolic extract.52
mimics the effects produced by calcium channel blockers, The reversal produced by the ginger juice was better than
Haniadka et al. 25
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