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ICT11110.1177/1534735411413266
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
Introduction
Despite significant progress in the field of cancer treatment, effective management of chemotherapy- and radiationinduced nausea and vomiting, abbreviated as CINV and
RINV respectively, is still a major problem as nearly 70%
to 80% of patients are affected.1 These complications are
the most feared adverse effects of these cytotoxic treatment
modalities and may compel the patient to opt out of the therapy. Severe nausea and vomiting at times leads to the development of complications such as fluidelectrolyte imbalances,
weight loss, dehydration, anorexia, weakness, fractures,
esophageal tears, prerenal azotemia, wound dehiscence, or
decline in behavioral and mental status.1
These adverse effects may deteriorate patients physical
and mental status, self-care, and functional ability and may
lead toward withdrawal from the anticancer treatment regimen. This will invariably affect the treatment outcome and
survival of the patient.1,2 It also increases patients anxiety
and dissatisfaction with the hospital experience and may
contribute to future anticipatory nausea.3 Depending on the
severity and frequency, nausea and vomiting are graded as
represented in Table 1.
Depending on the time after administration of the chemotherapy/radiotherapy, nausea may be classified as acute
nausea, which occurs within 24 hours after chemotherapy
and can be subdivided into early acute (within 12 hours) and
late acute (12 to 24 hours); delayed nausea, which appears
more than 24 to 96 or 120 hours after treatment; anticipatory nausea, which occurs before a new cycle of chemotherapy in response to conditioned stimuli, such as the
smells, sights, and sound of the treatment room and breakthrough nausea and vomiting that occurs despite preventive
therapy.1-3,5
The major factors that determine the incidence and severity of CINV include the dose and type of chemotherapy
1
Corresponding Author:
Manjeshwar Shrinath Baliga, Research and Development, Father Muller
Medical College, Father Muller Road, Kankanady, Mangalore 575002,
Karnataka, India
Email: msbaliga@gmail.com
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Haniadka et al.
Table 1. Gradation of the Nausea,Vomiting, and Anorexia4
Grade
0
1
2
3
4
Nausea
Vomiting
Anorexia
None
Able to eat reasonable intake
Intake reduced significantly
Very poor intake
None
1 episode in 24 hours
2 episode in 24 hours
Up to 10 episodes in 24 hours
>10 episodes in 24 hours. Requires parenteral support
None
Mild
Moderate
Severe
Life threatening
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Class of Antiemetics
the cannabinoids dronabinol, nabilone, marinol, and cannabis from Cannabis sativa commonly known as marijuana
is the best example.4 Scientific studies carried out in the
past 2 decades have shown that some of the most important
medicinal plants, for xample, Scutellaria baicalensis,
Korean red ginseng, American ginseng berry, Ganoderma
lucidum, Zingiber officinale, and grape seed extract possess
antiemetic action against CINV and mint oil and ginger
against RINV. In the following sections, the antiemetic and
antinausea observations are addressed.
Ginseng
Among all medicinal plants, globally, ginseng is probably
the most famous and extensively investigated plant. The
generic name Panax derived from the Greek word Panakos
means a panacea, a virtue ascribed to it by the Chinese, who
consider it a sovereign remedy in almost all diseases.12
Ginseng is a slow-growing perennial plant and the fleshy
root bears resemblance to the human body. Because of
this morphological feature, they are also known as manroot.13,14 There are 11 species of ginseng, but the most
important and the well-studied species are the Panax ginseng (Asian, Korean, or Chinese ginseng) and Panax
quinquefolius (also called American, Canadian, or North
American ginseng).14,15 In the United States, where the
market for medicinal botanicals is US$3 billion (CA$4.3
billion) and growing, ginseng is the top-selling herb among
first-time herbal users and ranks third, surpassed only by
Echinacea and garlic.16
In the traditional Chinese system of medicine, ginseng is
referred to as the ultimate tonic to benefit the whole body
and has been used for more than 2000 years.15 Ginseng has
been used to improve the bodys resistance to stress, to
increase vitality, increase general well-being, immune function, libido, and athletic performance. Preclinical studies
suggest it to possess adaptogenic, anti-inflammatory, antineurological, hypoglycemic, antineoplastic, immunomodulatory, cardiovascular, central nervous system, endocrine,
and ergogenic effects.14 In traditional medicine, ginseng is
also used for the alleviation of emesis.15 Preclinical studies
have shown that the Korean red ginseng (P ginseng)17 and
the American ginseng berry (P quinquefolius)18 prevent
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Haniadka et al.
Table 3. Side Effects of Antiemetics Commonly Used in the Prevention of CINV and RINV
Class of Antiemetic
5-HT3 receptor antagonists
Phenothiazines
Antidopaminergic drugs
H1 antihistaminics
Corticosteroids
Muscarinic receptor
antagonists
Drugs
Ondansetron, tropisetron,
granisetron, dolasetron,
palonosetron, ramosetron
Prochlorperazine, promethazine,
thiethylperazine
Neuroleptics: Chlorpromazine,
Prochloropropazine
haloperidol, droperidol
Prokinetic drugs: Cisapride,
mosapride, tegaserod,
fluphenazine, domperidone
diphenidol
Substituted benzamides:
Metoclopramide,
trimethobenzamide
Dimenhydrinate, clizines,
cinnarizine, diphenhydramine,
promethazine, hydroxyzine,
meclizine, doxylamine
Dexamethasone,
betamethasone,
methylprednisolone
Scopolamine, dicyclomine
diphenidol
Benzodiazepines
Diazepam, lorazepam,
alprazolam
Cannabinoids
NK1 antogonists
Aperpitant
Casopitant
Fosaprepitant
Maropitant
Vestipitant
Adverse Effects
Diarrhea, headache, light-headedness, asthenia, abdominal
discomfort, rash and allergic reaction
Drowsiness, hypotension, impaired psychomotor activity,
agitation, insomnia, inversion of sleep, postural hypotension,
paroxysmal tachycardia, blurred vision, dry mouth,
constipation, paralytic illus, perspiration, hyperglycemia
Abbreviations: CINV, chemotherapy-induced nausea and vomiting; RINV, radiotherapy-induced nausea and vomiting; HPA axis, hypothalamicpituitaryadrenal
cisplatin-induced nausea and vomiting in experimental animals. The following section addresses these aspects.
22
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Haniadka et al.
baicalensis and its binding to 5-HT1A receptors.30,32 Similar
results were also observed in another study and the reported
in vitro free radical scavenging effects of the extract confirmed that the antioxidant action of the herb may be, at
least in part, responsible for attenuating the cisplatininduced nausea and vomiting.22
24
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Haniadka et al.
Conclusions
Numerous preclinical studies in the past 2 decades have
demonstrated unequivocally that traditionally used plants
such as S baicalensis, Korean red ginseng, American ginseng
berry, G lucidum, ginger, and grape seed extract possess
antiemetic actions against CINV, and mint oil and ginger
against RINV. Most of the antiemetic studies against CINV
have been with cisplatin and future studies are required with
other chemotherapeutic agents and their combinations that
26
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
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