Chiara Bertaggia and Chiara Penengo
PLANT DESCRIPTION
Common ginger, Zingiber officinale Roscoe, is a member of the family of Zingiberaceae, which comprises at least 800 different species.
The consumed portion of the ginger plant is the rhizome, often called “ginger root”, although it is not actually a root. The rhizome is the horizontal stem of the plant that sends out the roots.
There is a large number of variants (subspecies), which differ primarily in the smell and colour. The ginger is a monocotyledonous plant (that is, with the leaf to a single seed) of the tropics, that grows mainly in Southeast Asia.
It is a perennial herb, characterized by its very robust and fleshy rhizome with thin lateral roots.
Ginger is grown primarily in Asia and tropical areas and, in addition to its culinary function, has been used since ancient times for a variety of conditions, including colds, fevers, and digestive problems, and as an appetite stimulant. It is categorized by the U.S. Food and Drug Administration as a food additive but has been studied as a treatment for nausea and vomiting, as well as for arthritis.
ACTIVE MOLECULES DESCRIPTION
Ginger contains a number of pungent constituents and active ingredients.
The major pungent compounds in ginger, from studies of the lipophilic rhizome extracts, have yielded potentially active gingerols, which can be converted to shogaols, zingerone, and paradol.
Shogaol is formed by dehydration of corresponding gingerols during storage or thermal processing.
The compound 6-gingerol appears to be responsible for its characteristic taste. Zingerone and shogaols are found in small amounts in fresh ginger and in larger amounts in dried or extracted products.
The gingerols may be the major active principles in ginger that inhibit platelet activation and platelet aggregation.
INDICATIONS
Ginger, the powdered rhizome of the herb Zingiber officinale, is widely used as a spice around the world. For centuries it has been used in Chinese, Ayurvedic and Tibb-Unani herbal medicine.
In the Ayurvedic medicine ginger has been used as a treatment for rheumatism, nervous disease, asthma, stroke and diabetes.
EFFICACY OF GINGER FOR NAUSEA AND VOMITING
Probably the most known ginger’s property is the antiemetic effect, but the mechanism underlying ginger’s anti-emetic activity is not clearly understood.
However several studies demonstrated this important effect.
MOTION SICKNESS
Grontved and coll. (Ginger root against seasickness. A controlled trial on the open sea., 1988) studied 80 Danish cadets, allocated randomly to receive either ginger or placebo. Volunteers who received ginger suffered less seasickness compared with those who received placebo. However ginger did not reduce the number of participants reporting vertigo.
POST SURGICAL NAUSEA
Bone and coll. (Ginger root--a new antiemetic. The effect of ginger root on postoperative nausea and vomiting after major gynaecological surgery., 1990) studied 60 women before major gynaecological operations. Patients were allocated randomly to receive ginger (1g), metoclopramide (10mg) or placebo as a single dose given with preoperative medication. The incidence of nausea during the first 24h after surgery was 28%, 30% and 51% in the ginger, metoclopramide and placebo groups respectively.
In a recent double-blind study, instead, ginger failed to demonstrate an anti-emetic effect following laparoscopic surgery.
CHEMOTHERAPY-INDUCED NAUSEA
Cancer chemotherapy can cause severe nausea and vomiting, which can limit therapy. Anticancer agents such as cisplatin, cyclophosphamide, and methotrexate slow gastric emptying. In a double-blind study of chemotherapy-induced nausea, 41 patients with leukemia received either ginger or a placebo after administration of compazine. The results showed a significantly greater symptomatic benefit from ginger compared to placebo.
Moreover, in a study on rats, following cisplatin administration, significant inhibition of gastric emptying occurred. The inhibitory effects of gastric emptying were partially reversed by pretreatment with ginger extract and ginger juice. Similar efficacy of these ginger preparations was also observed in antiemetic studies against cisplatin-induced emesis in dogs.
NAUSEA AND VOMITING IN PREGNANCY
Prescription drugs are usually avoided in early pregnancy due to fear of fetal abnormalities. There is consequently increasing interest in alternative therapies for this condition.
Fischer-Rasmussen and coll. (Ginger treatment of hyperemesis gravidarum., 1991) conducted a study in 27 women suffering from hyperemesis gravidarum. Patients received ginger or placebo and the results suggested a significantly greater symptomatic benefit after administration of ginger compared with placebo.
However the use of ginger in pregnancy is argued. According to some authors, research has not adequately addressed whether ginger is safe for developing fetuses. Animal studies have shown ginger to be a potent thromboxane synthetase inhibitor; it could affect testosterone receptor binding and sex steroid differentiation in the fetal brain.
Moreover, the German monograph warns that ginger should not be taken during pregnancy. The caution is based on data suggesting that ginger is mutagenic in several test system.
In an Australian study (Effect of a ginger extract on pregnancy-induced nausea: a randomised controlled trial., 2003) about ginger’s antiemetic effect in pregnancy, authors practiced a follow up in their patients, in order to see possible dangerous effects on mothers or child. The frequency of neonatal death was similar to the normal. The rates of birth defects were similar to general population and there was also no difference in the rates of post-partum haemorrhages (although ginger is known to decrease thromboxane synthesis in vitro).
ANTI-INFLAMMATORY AND ANTI-THROMBOTIC EFFECTS
Ginger extracts also have an anti-inflammatory, antithrombotic and antioxidant effects and have been reported to be effective at reducing the symptoms of arthritis in humans.
Gingerols inhibit human platelet activation, because they inhibit the arachidonic acid (AA)-induced platelet release reaction and aggregation.
Ginger, for his anti-inflammatory effect, may be used to reduced inflammation instead of non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit the enzyme responsible for production of arachidonic acid metabolites, but they have many adverse side effects (e.g. gastric ulcers and gastrointestinal bleeding), which may be ameliorated by the use of effective botanical alternatives.
Aspirin, a NSAIDs, is also used as an antiplatelet therapy, but it has many adverse effects. Thus, research and development of new antiplatelet drugs with a more favourable adverse effects profile are required. For this reason, gingerols and related analogues may be used as an alternative antiplatelet therapy.
PHARMACOKINETICS
Ginger can be consumed as a fresh or dried root and is often prepared in teas, soft drinks (including ales), and breads.
A typical dose of ginger is between 250 mg and 1 g of the powdered root in capsular form, taken one to four times daily.
To prevent motion sickness it’s best to begin treatment 1-2 days before the trip and continue dosing during the travel.
For nausea and vomiting during pregnancy, ginger tea, made from fresh ginger root, appears to work best.
MOLECULAR MECHANISM
ANTIEMETIC EFFECT
The exact mechanism of action of ginger in relation to its antiemetic properties is unclear, but it is possible that it has direct effect on the gastrointestinal tract.
In animal model it was demonstrated that 6-gingerol anhanced gastrointestinal transport. Galanolactone, another constituent of ginger, is a competitive antagonist at ileal 5-HT3 receptor (chemotherapy-induced nausea is linked with activation of 5-HT3 receptor and some antiemetic agents, as odansetron, are based on this mechanism). A mechanism involving the central nervous system cannot be ruled out, but this is not been clearly demonstrated. Studies do not indicate ginger has influence within the vestibular or oculomotor system.
ANTI-INFLAMMATORY AND ANTI-THROMBOTIC EFFECTS
Inflammation is associated with a large range of mediators that initiate the inflammatory response. Cytokines, regulatory peptides that are produced by all cells, in general are not constitutively produced; LPS (lipopolysaccharide) from Gram – bacteria increases gene expression and production of the cytokines.
TNF-alfa and IL-1 are two of major cytokines involved in the initiation of inflammation: they induce the expression of other cytokines, the activation of arachidonic acid metabolism and the priming of PMN.
In addiction, metabolites of arachidonic acid also participate in the inflammatory process. Arachidonic acid can be metabolized by lipooxygenase or cyclooxygenase. Lipooxygenase leads to production of leukotrienes; ciclooxygenase produce prostaglandins and thromboxanes.
Increased production of prostaglandins during an inflammatory process is achieved by induction of cyclooxygenase-2 (COX-2).
Gingerols and a number of gingerol derivatives inhibit the prostaglandin and leukotriene synthesis enzyme when tested in vitro, because they directly inhibit COX-1 and COX-2 activity.
Moreover, gingerols interact with transcription factors that regulate the inflammatory gene expression, like NF-kB and AP-1. LPS induction of inflammatory mediators will activate these transcription factors leading to increased gene expression and protein for TNF-alfa, IL-1, IL-12, iNOS and COX-2 (Lantz et al., 2007).
Many studies shown that ginger rhizome was able to inhibit LPS-induced production of PGE2.
Lantz et al. (The effect of extracts from ginger rhizome on inflammatory mediator production., 2007) demonstrated that gingerols, to inhibit the production of PGE2, have two sites of action: inhibition of COX-2 gene expression (decrease of COX-2 mRNA levels) and direct inhibition of COX-2 enzyme activity.
Tripathi et al. (Ginger extract inhibits LPS induced macrophage activation and function.,2008) observed a significant decrease in the LPS induced production of TNF-alfa, IL-12 and IL-1 in presence of ginger extract treatment.
They observed a decrease of almost 10 fold in TNF-alfa production in macrophages treated with ginger extract in presence of LPS stimulation; moreover IL-1 and IL-12 production were inhibited.
The inhibition of arachidonic acid metabolism and the inhibition of ciclooxygenase activity also lead to the inhibition of platelet activation and aggregation.
A study (Gingerols and related analogues inhibit arachidonic acid-induced human platelet serotonin release and aggregation., 2001) examined the ability of gingerols to inhibit human platelet activation, compared to aspirin, by measuring their effects on arachidonic acid induced platelet serotonin release and aggregation in vitro. The study revealed that gingerols and related analogues were two-to three-fold less potent than aspirin against the platelet release reaction initiated by arachidonic acid, and two- to four-fold less potent than aspirin at inhibiting arachidonic acid induced platelet aggregation.
The inhibition of COX-2 caused this anti-thrombotic effect. COX-2 converts the arachidonic acid into prostaglandins; prostaglandins are converted into thromboxane A2 by thromboxane synthase.
Arachidonic acid is an important element in the platelet activation and aggregation process. PGG2, PGH2 and thromboxane A2, the arachidonic acid metabolites, are potent platelet activators.
SIDE EFFECTS
Ginger extracts exhibit inhibition of platelet aggregation and thromboxane synthesis, which has led to concerns ginger extracts may prolong bleeding. So it may be prudent for patients taking anticoagulants such as warfarin (Coumadin) to exercise caution.
Some studies reported a possible mutagenic effect, so we can’t be sure about its safety in pregnancy.
Ginger has been reported to have positive inotropic effects in animal models and has also led to case reports of arrhythmia. Although there have been no reports of toxic effects from ginger after human consumption, more research analyzing adverse reactions and potential drug interactions needs to be performed.
