Ginger

FAMILY: Zingiberaceae.

HABITAT: originating in India, it is currently cultivated in South-East Asia, South China, the West Indies and Africa.

USED PART: the rhizome.

RECOMMENDED PHARMACEUTICAL PREPARATION: the dry extract is titrated in essential oil min. 0.8 % (B.H.P. 1990) or in gingerols min. 4% (German Commission E), The daily dosage used in studies published in the literature is 12-13 mg/kg/day, divided into two administrations, preferably on an empty stomach. As these studies were conducted with different extracts with different titres, the above posological value represents an indicative average value.

CHEMICAL COMPOSITION: the rhizome of ginger is very rich in starch (about 60%) and contains a fair amount of essential oil, between 0.8 and 2%. The constituents responsible for the typical taste of the drug are called gingerols.

THERAPEUTIC PROPERTIES:
Anti-emetic action: This drug has been shown in studies conducted in both animals and humans to have aninteresting anti-emetic action.
A direct effect of the drug on the central nervous system, as is the case with classic anti-emetic drugs, seems to be ruled out, so the anti-nausea action of ginger would appear to be due to its activity at the gastric level.
Moreover, a study carried out in rats seems to show that the anti-nausea action of ginger may be due, at least in part, to an antiserotonergic activity.
Clinical Trials
- A controlled clinical study investigated the effect of ginger onhyperemesis gravidarum. One hundred and twenty women were enrolled, who had been pregnant for no more than 20 weeks and who had obvious nausea gravidarum, which had not improved with a correct dietary approach. They took either 125 mg/day of a ginger extract titrated to 5% gingerols per os or a placebo for 4 days. The frequency and intensity of nausea and vomiting was measured using the Rhodes Index of Nausea, Vomiting and Retching. It was noted that the frequency and intensity of nausea was significantly lower in women in the ginger group as early as the second day of therapy, while there was no noticeable effect on vomiting. The women were followed up until delivery to assess the incidence of abnormalities in newborns. No increase in abnormalities was noted in newborns compared to the control population, indicating that ginger is an effective and safe remedy for hyperemesis gravidarum.

- Another controlled clinical trial investigated the efficacy and safety of ginger extract in pregnant nausea. 187 women were enrolled in the first trimester of gestation, part of whom were taking ginger extract and part of whom were taking other anti-nausea substances that were certainly not teratogenic. The women were then followed until delivery to document any incidence of foetal malformations. The assessment was made using an analogue scale from 1 to 10, to evaluate the frequency and severity of nausea and vomiting crises. With regard to efficacy, 66% of the women indicated a marked improvement in symptoms after ginger therapy. The number of normal term births was 181, the number of premature births 2, the number of miscarriages 3 and the number of therapeutic abortions 1. There were no differences between women in the ginger group and those treated with other substances recognised as non-teratogenic. The average birth weight of babies from women in the ginger group was 3542 g. compared to 3500 g. from those in the other group. The study confirms that ginger is reasonably effective in hyperemesis gravidarum and does not increase the incidence of malformations in newborns.

- Nausea is one of the most common side effects of cancer chemotherapy. It has been noted that foods high in protein reduce nausea due to motion sickness or seasickness or pregnancy, possibly by reducing dysrhythmia of the stomach. In this study, theeffect of a high-protein diet combined with a ginger extract was investigated in patients with nausea following chemotherapy. Twenty-eight patients were enrolled, who had to follow either a normal diet or a high-protein diet supplemented with ginger extract. Patients had to record in a special notebook the frequency and intensity of their nausea and whether they needed anti-emetic medication. The myoelectric activity of the stomach on an empty stomach and after a meal was also measured. It was noted that in patients on a high-protein diet supplemented with ginger extract, the frequency and intensity of nausea and the use of anti-emetic drugs were significantly less frequent. The addition of ginger extract reduced gastric dysrhythmia after food ingestion. The study indicates that a high-protein diet combined with ginger extract is effective in reducing nausea from cancer chemotherapy.

- Another controlled clinical trial evaluated the effect of a ginger extract on nausea following cancer chemotherapy. 162 patients treated with antiblastic chemotherapy, receiving a 5-HT(3) receptor antagonist and/or aprepitant, were enrolled. They also had to take 1 or 2 g/day of ginger extract or a placebo for 3 days, measuring the frequency and intensity of nausea and vomiting. It was found that there were no statistically significant differences between the groups with regard to nausea or vomiting. Patients treated with aprepitant + ginger had more acute nausea than those taking aprepitant alone. Ginger was very well tolerated. The study indicated that a ginger extract did not improve nausea and vomiting following cancer chemotherapy when administered together with a 5-HT(3) receptor and/or aprepitant.

Antiphlogistic action:This antiphlogistic action is due to inhibition of both 5-lipo-oxygenases and cyclo-oxygenases, resulting in inhibition of the formation of both leukotrienes and thromboxanes as well as prostaglandins with inflammatory action, with a mechanism of action similar to that of NSAIDs.
Oedema in the rat paw induced by carrageenan, compound 40/80 or serotonin was well antagonised by ginger extract given intraperitoneally. Moreover, the extract in question was capable of inhibiting the skin oedema induced by compound 40/80, but not that caused by substance P or bradykinin. Ginger extract given 1 hour before serotonin significantly inhibited serotonin-induced skin oedema. The data presented in this study indicate that the protective action of hydroalcoholic ginger extract on inflammation and skin oedema induced by the substances used here may be due to an antagonism with serotonin receptors in the skin.
 - One study on rat assessed the antiphlogistic, analgesic and hypoglycaemic action of a ginger extract. The analgesic effect was examined using hot plate and acetic acid tests, while the antiphlogistic and hypoglycaemic effects were investigated using egg albumin-induced paw oedema and diabetes mellitus caused by streptozotocin. As a comparison, morphine at a dose of 10 mg/kg or diclofenac at a dose of 100 mg/kg or chlorpropamide at a dose of 250 mg/kg was used. It was seen that ginger extract at doses between 50 and 800 mg/kg significantly reduced the pain induced by the hot plate test and acetic acid (p<0.001) and also inhibited the inflammation in paw oedema induced by egg albumin (p<0.001). It also lowered blood glucose in both normal rats and those made diabetic with streptozotocin. The study confirms that ginger extract possesses antiphlogistic, analgesic and hypoglycaemic action in the rat.

- A study in the rat evaluated the antiphlogistic action of two topically applied ginger extracts. This consisted of a classic hydroalcoholic extract and a hydroalcoholic extract enriched with gingerols, the antiphlogistic action of which on the skin against inflammation induced by croton oil was investigated. The study was conducted both ex vivo using rat skin or human epidermis and in vivo in the animal. It was seen that the acetone solution of these extracts had a remarkable antiphlogistic action, with an ID50 of 142 mug/cm2, not far from that exhibited by indomethacin taken as a comparison (93 mug/cm2). The extract enriched in gingerols showed no superior antiphlogistic action to the classic extract. Medicated plasters containing a dose of ginger extract of 1 mg/cm2 were also tested, which showed to have a valid anti-inflammatory action. In the ex vivo study, the amount of 6-gingerol penetrating human skin was 6.9 mug/cm2, while that penetrating rat skin was 22.1 mug/cm2. The study indicates that ginger extract has a good antiphlogistic action in both rat and human skin.

- A study in the rat showed that an aqueous extract of ginger hindered Th2-mediated pulmonary inflammation. Its intraperitoneal injection prior to airway stimulation with ovalbumin caused a marked reduction of eosinophils in the airways and a reduced inflammatory response in the airways. This effect was accompanied by suppression of the Th2-type response to the allergen, with a marked reduction in IL4, IL5, eotaxin and specific IgE levels in the airways. The most effective substance for this was 6-gingerol. The study indicates that an aqueous extract of ginger suppresses the Th2-type immune response and thus may have beneficial effects in allergic asthma.

Clinical Trials
- A clinical study was conducted on 56 patients, including 28 with rheumatoid arthritis, 18 with osteoarthritis and 10 with muscular disorders, who received 7.6 g fresh ginger daily for a period of 3 months. At the end of the trial, all subjects with muscular disorders and osteoarthritis showed consistent improvements, which were present in 75% of those with rheumatoid arthritis. It also appears that dry ginger extract is useful as a preventive and prophylactic in patients suffering from recurrent headache attacks.

- A controlled clinical trial evaluated the effect of dry ginger extract in patients with osteoarthritis of the shoulder or knee. They received per os ginger extract or ibuprofen or a placebo for a 3-week cycle, followed by a 7-day interval and two more similar cycles. Acetaminophen was used as an emergency remedy for acute algic crises. The assessment was made using Friedman's analogue pain scale and Lequesne's index. At the end of the trial it was seen that both ginger and ibuprofen gave better results than placebo, with a statistically significant advantage for ibuprofen. The superiority of ginger over placebo was modest but still significant. No notable side effects were recorded in any of the three groups tested (10B).

- A clinical study compared the effect of a ginger extract to that of mefenamic acid andibuprofen in women suffering from dysmenorrhoea. A total of 150 women were enrolled, who had to take 1 g/day of ginger extract or 250 mg/day of mefenamic acid or 400 mg/day of ibuprofen per os during the first three days of their menstrual cycle. The severity of dysmenorrhoea was assessed by means of an appropriate pre- and post-therapy questionnaire. It was seen that, at the end of the trial, there was a significant decrease in symptoms in all three groups studied, with no statistically significant differences between one group and the other. No obvious adverse effects were noted in any of the three groups studied. The study indicates that a ginger extract has overlapping efficacy with mefenamic acid and ibuprofen in relieving dysmenorrhoea and is very well tolerated.

Gastroprotective action: a group of rats was treated with a solution of ethanol, hydrochloric acid and sodium chloride or with gastrolesic drugs such as acetylsalicylic acid, indomethacin and reserpine to induce gastric lesions and evaluate the effect of ginger extract on them. At a dose of 500 mg/kg/day per os it resulted in effective gastroprotection in approximately 85% of the gastric lesions induced by the above-mentioned substances, probably with a peripheral action at the level of the gastric mucosa.
Helicobacter pylori is known to be one of the main causes of peptic ulcers, along with oxidative stress and anti-inflammatory drugs. In this in vitro study, the effect of the polyphenol fraction of ginger and a polyphenol-free ginger extract on Helicobacter was examined. It was seen that both extracts significantly inhibited this germ with an IC50 of 2.9 mug/ml, with 6-8 times the potency of lansoprazole. The ginger extract without the phenolic fraction contained mainly syringic acid (38%), gallic acid (18%) and cinnamic acid (14%), while the phenolic fraction of ginger was rich in cinnamic acid (48%), p-cumaric acid (34%) and caffeic acid (6%). Both extracts used had a valid scavenger action with an IC50 of 1.7 mug/ml and validly inhibited lipoperoxidation with an IC50 of 3.6 mug/ml. The study indicates that both extracts used here could be useful in combating peptic ulcer.

- A hydromethanolic extract of ginger exerts prokinetic action at the stomach fundus through activation of the post-synaptic muscarinic M3 receptor. Ginger extract placed in the culture fluid of stomach strips at doses of 0.01 or 0.1 mg/ml increased their response to the contractile effect of carbacol and increased their contractile force, showing that this effect could be due to inhibition of presynaptic muscarinic receptors. Pirenzepine, a presynaptic M1 muscarinic receptor antagonist, and himbacin, a presynaptic M2 muscarinic receptor antagonist, also potentiated the contractile effect of carbacol. The study indicates that ginger, in addition to its agonist action on post-synaptic M3 cholinergic receptors of the gastric fundus, may also act as an antagonist of presynaptic M1 and M2 muscarinic receptors, which explains its stimulating actions on the gastric musculature.

- A controlled clinical study evaluated the effect of a ginger extract on stomach motor function, gastric emptying, antral motility, stomach volume and postprandial symptoms. Twenty-eight healthy volunteers were enrolled, who had to ingest 1200 mg of ginger extract or a placebo in the morning on an empty stomach, followed after 1 hour by 500 ml of a low-nutrient soup. It was seen that in the verum group, the antral area was reduced more rapidly (p<0.001) and the stomach emptying time was shorter (p<0.01), while the frequency of antral contractions was higher (p<0.05), also in the verum group. Stomach volume and postprandial symptoms were similar in both groups. The study indicates that a ginger extract accelerates the emptying of the stomach and stimulates antral contractions in the healthy volunteer.

Main indications: nausea and vomiting of any origin, motion sickness, gastritis and gastroduodenitis.

Prevalent action: anti-nausea and anti-emetic.

Other actions: gastroprotective.

SIDE EFFECTS: High dosages may cause rash.

CONTRAINDICATIONS: none worth mentioning.

DRUG INTERACTIONS: It may potentiate the effect of antiplatelet drugs and oral anticoagulants, as it is an inhibitor of the enzyme thromboxane synthase.

- Another study in rats tested the effects of administering a ginger extract on blood glucose, coagulation parameters, blood pressure and heart rate. It was seen that none of these parameters were modified by the drug in question, nor was the action of warfarin on coagulation parameters.
A clinical case of interaction between ginger and phenprocumone was reported in this paper. This was a 76-year-old white woman, who had been taking taking phenprocumone or a long time and had an INR in the therapeutic range. After taking the ginger extract, theINR had increased abnormally, with epistaxis occurring. Everything returned to normal by discontinuing ginger and administering vitamin K.

- A study in humans investigated the effect of ginger on warfarin. Twelve healthy volunteers were enrolled, taking 25 mg warfarin per os for 7 days and then an adequate dose of ginger extract. The following parameters were monitored: platelet aggregation, INR, prothrombin time and warfarin plasma concentrations. It was seen that ginger extract at the correct doses did not significantly change any of theparameters examined.

TOXICOLOGICAL DATA: A group of rats received dry ginger extract orally at doses of 100, 333 and 1000 mg/kg/day between days 6 and 15 of gestation, after which the animals were sacrificed and the foetuses thoroughly examined on day 21 of gestation.  No alterations of any kind were noted in any of the organs examined, either in the foetus or in the mother.
Based on the data in the literature today, this drug can be used during pregnancy.

- A study in the rat assessed the sub-chronic toxicity of a ginger extract administered for 35 days at doses of 500 or 1000 or 2000 mg/kg/day. It was noted that the drug did not cause increased mortality and visible changes in the animals, nor did it cause changes in their ingestion of food and water. Haematochemical examinations were not altered by ginger extract, with the exception of a modest increase in plasma LDH levels. Only the 2000 mg/kg/day dose caused a modest reduction in testicular weight. The study indicates that the sub-chronic toxicity of ginger is very low.

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