ZINGIBERACEAE

The Zingiberaceae or Ginger family are monocotyledons. The family consists of about 40 genera of rhizomatous herbs growing throughout the tropics.

• Stems are usually erect or cane-like, growing in clumps
• Leaves are elongate, entire, with parallel or pinnate veins, with the base partly or completely sheathing the stem
• Inflorescence is a head, spike or panicle either on a separate stalk or terminating a leafy stem
• Flowers are irregular, calyx and corolla tubular, each 3-lobed, and 1 fertile stamen enfolding the style

Medicinal and culinary plants of the Zingiberaceae include the genera Alpinia, Amomum, Curcuma, Elettaria and Zingiber.

Zingiber officinale

Ginger

Description

A herbaceous perennial monocotyledon, ginger grows to about 1 m rising from a coarse, irregular, Family Zingiberaceae tuberous rhizome. Stems are smooth and reedlike with alternate light green leaves, 20 × 2 cm sheathing the stem. Flowers are borne in spikes on shorter leafless stems about 30 cm tall. The spike consists of numerous greenish-yellow imbricated bracts from behind which the flowers are produced. They are not numerous, and are yellow speckled with purplish dots and generally have a purple lip. Fruit is an oblong capsule which breaks open irregularly.

Family Zingiberaceae

Odour—characteristic and aromatic; taste—pungent and aromatic.

Habitat and cultivation

Native of tropical Asia and widely cultivated in other tropical areas. Grown from division of the rhizomes in rich, moist soil and semi-shade. Drought and frost tender.

Parts used

The rhizome is harvested after the plant dies back and used fresh or dried. There are a number of main cultivars of Z. officinale used medicinally and 2 other morphologically similar species, Z. zerumbet and Z. cassumunar, that are sometimes used as “adulterants” of Z. officinale.1

Active constituents

1) Volatile oil (1–4%). At least 54 constituents have been identified comprising mono- and sesquiterpenes. Although the composition can vary its main constituents usually include α-zingiberene, ar-curcumene, β-sesquiphellandrene, β-phellandrene, β-bisabolene, camphene and geranial.^2–7 These are responsible for the aroma of the herb⁴

2) Phenolics which give the herb its pungency^8,9 and include:

a) arylalkanones the main ones are gingerols of which [6]-gingerol is the most abundant (around 6%)¹⁰ with [8]-gingerol and [10]-gingerol, shogaols^11,12 including [6]-shogaol also paradols, gingediols, gingediacetates, gingerdiones, gingerenones and zingerones^11–17

b) phenylpropanoids including diarylheptanoids of which at least 26 have been identified^18,19

c) phenolic acids including syringic, gallic, cinnamic, vanillic and ferulic acids^20,21

Zingiber's oleoresin accounts for between 4–8% of the crude herb and is made up of approximately 25% volatile oil, 33% phenolics,²² fats and waxes.

Also contains proteases including zingibain,^23,24 steroids,⁹ starch,²⁵ indolic compounds (melatonin, tryptamine and serotonin),^26,27 flavonoids,²⁸ saponins, alkaloids, lipids (9%)²⁹ and small amounts of salicylate.³⁰

Cultivars may differ in their relative content of active constituents³¹ and geographical origin, method of processing, analytical procedure and freshness of starting material can affect the final chemical make-up.^4,32–35 Although the quantitative chemistry of constituents within the species varies with genetic origin the qualitative make-up is apparently quite consistent.^8,36,37 On the other hand the different species are qualitatively different and therefore distinguishable.³⁶

Fresh and dried ginger—The essential oil content does not differ very markedly between dried and fresh ginger³⁸ and the gingerols are still the predominant pungent constituents in the dried form.¹⁶ The shogaols are produced from dehydration of their corresponding gingerols as Zingiber is dried, heat-processed or stored long-term, [6]-shogaol forms from [6]-gingerol and so on through the series.^12,39 Shogaols are not present to any extent in the fresh material³⁷ but their level increases in dried ginger as the level of gingerols decrease.¹¹ Once extracted both constituents are relatively stable by avoiding high temperatures. In vitro models found that in conditions that reflect the pH and temperature found in the stomach [6]-shogaol may be substantially converted back to [6]-gingerol.³⁹

On storage the content of ar-curcumene increases whilst zingiberene and β-sesquiphellandrene decrease.²²

Nutritional constituents

Vitamins: A, B-complex and C

Minerals: Calcium, iron, phosphorus, sodium, potassium and magnesium⁴⁰

Actions

1) Carminative

2) Anti-emetic

3) Spasmolytic

4) Peripheral circulatory stimulant

5) Anti-inflammatory

6) Diaphoretic

Scientific information

Ginger has been used for over 2500 years as a medicine and spice and the demand for it today is high as it is not only valued for these purposes but is also used in the cosmetic industry. It is one of the most widely used food spices in the world and is a frequent constituent of Chinese and Ayurvedic formulations. The name ginger derives from the Sanskrit word “sringavera” (relating to the shape of the root) which was transformed to the English name “ginger”.41

It has been and is still an official preparation in a number of pharmacopoeias worldwide⁴² and is approved in Germany by Commission E for the treatment of dyspepsia and to prevent motion sickness. Much of the research into the herb has been conducted over the last 50 years.

[6]-gingerol, as ginger's main constituent, has been particularly well studied, however at least 400 constituents have been characterised from the extract, many of them are pharmacologically active and no doubt they also have synergistic actions that contribute to the herb's overall actions.⁴³

About 80% of the world production of ginger comes from China.

Anti-oxidant

In vitro—The herb as well as more than 50 of its individual constituents⁴⁴ have very good anti-oxidant and radical scavenging activity^{17,18,45–52} including against nitric oxide⁵³ and lipid peroxidation.^44,54–57 It appears likely that after absorption through the gastro-intestinal tract this antioxidant activity is retained though possibly at a reduced level.⁵⁸

Zingiber has displayed cell protecting activity for a range of different cell types and this may be due, wholly or in part, to its anti-oxidant potential. Although most studies used animal models⁵¹ it did also protect human red blood cells from the toxic effect of parabens (p-hydroxybenzoic acid).⁵⁹

Anti-inflammatory

In vitro—The gingerols, shogaols and paradols have been credited with many of ginger's anti-inflammatory properties⁶⁰ although the full extent of actions and constituents responsible still remain to be uncovered. It is very likely that the constituents act synergistically to produce this activity.³⁶

Mechanisms behind the anti-inflammatory action are likely to include:-

• strong inhibition of COX-1 and COX-2 enzymes with reduced production of prostaglandins and thromboxanes from arachidonic acid.^16,60–63 Ginger and to a lesser extent individual phenolic constituents reduce COX-2 synthesis in addition to inhibiting its activity⁶⁴
• inhibition of 5-LOX and the metabolism of arachidonic acid to leucotrienes^63,65
• antioxidant—oxidation may help fuel inflammatory reactions⁷¹
• blocking of various inducers of genes coding for pro-inflammatory cytokines—this was demonstrated in synoviocytes from osteoarthritic joints.^66,67 (The action of the herb on some cytokine production may be complex, in one study it was biphasic—augmenting cytokine production at low concentration, inhibiting it at higher levels. In addition augmentation increased over time, after initial ginger exposure)⁶⁸
• agonist action at vanilloid receptor sites TRPV1 (see Capsicum)—some of the gingerols and shogaols, particularly [6]- and [8]-gingerol, have a vanillyl moiety that behaves like capsaicin (See Capsicum) although they are less potent^69,70

(Dual inhibition of COX and LOX reduces the potential for side-effects and should make the anti-inflammatory activity more effective^71,72).

Ginger combined with galangal (Alpinia galangal) inhibits gene-induced inflammatory cytokine production in cells similar to microglial cells, suggesting a possible protective effect against inflammation-induced neurodegenerative diseases.⁷³

[6]-gingerol can permeate through epidermal tissue to some extent.⁷⁴ It inhibits UVB-induced COX-2 activity (so may be photo-protective)⁷⁵ and increases anti-inflammatory enzyme activity in prostate cells.⁷⁶

In vivo—There are not many clinical trials assessing the anti-inflammatory effects of ginger. Early studies on its use to treat arthritis, both osteo- and rheumatoid, had found it was beneficial in reducing pain and swelling being especially useful for discomfort in muscles.71,77 More recently it improved arthritis of the knee joint (gonarthritis) after 6 months use.⁷⁸

Other reported trials have used Zingiber in combination with various herbs. Combinations with A. galangal⁷⁹ and with Withania somnifera, Boswellia serrata and Curcuma longa⁸⁰ both produced symptomatic improvement in osteoarthritis of the knee. The ginger/galangal combination used for a three week period to treat osteoarthritis of hip or knee though beneficial was less effective than ibuprofen.⁸¹

Anti-emetic

Although the anti-emetic property of ginger was used traditionally and is one of the modern uses to be officially endorsed in Germany,⁸² the mechanisms behind this action are not fully understood. The active constituents for antiemesis appear to be the main gingerols and [6]-shogaol and probably some of the other more minor arylalkanones.^83,84 Proposed mechanisms are largely based on investigations using animal models and include⁸³:-

• a central mechanism—this does not seem very likely as ginger has no effect on vestibular optokinetic nystagmus⁸⁵ and it does not cause drowsiness like other centrally-acting anti-emetics⁸⁶
• inhibition of neurotransmitters known to induce nausea—serotonin,^83,87 neurokinin,⁸³ acetylcholine and/or histamine.⁸⁸ 5-HT₃ receptors are involved in acute nausea/vomiting and neurokinin receptors are involved in delayed and acute nausea/vomiting, chemotherapy induces both neurotransmitters⁸⁹
• by increasing gastro-intestinal motility and reducing feedback to central chemo-receptors—motion sickness slows gastric emptying and alters gastric motility.⁹⁰ In vivo ginger has been shown to increase gastro-duodenal motility in a fasting state and after a meal⁹¹ but does not increase the rate of gastric emptying^90,92
• prevention of gastric dysrhythmia and raised levels of vasopressin⁹³—both events occur in motion sickness.⁸⁸

In vivo—Ginger has been used in clinical trials to treat nausea of varying origin.

It has been well tested for alleviating nausea in early pregnancy as at this stage it is possible to avoid progression to hyperemesis gravidarum.⁹⁴ It was effective to varying degrees for the treatment of both nausea and vomiting in early pregnancy^95–98 being as good as, or better than vitamin B6^99–101 and as effective as dimenhydrinate with fewer side effects.¹⁰² It was also an effective treatment for hyperemesis gravidarum.¹⁰³

In post-operative nausea and vomiting it gave inconsistent results with some studies showing a positive benefit^104–109 and others showing no improvement compared to placebo.^{110–114,124}

For nausea due to chemotherapy ginger was effective as a prophylactic¹¹⁵ with fewer side-effects than conventional anti-emetics.¹¹⁶

In assessing ginger's efficacy in treating motion sickness (kinetosis), most studies used a simulator to induce the condition. Zingiber preparations gave a range of results from lack of effect^90,117 to effects superior to dimenhydrinate¹¹⁸ and placebo.⁹³ It reduced nausea, prolonged time to its onset and shortened recovery time after motion ceased.⁹³ In actual sea travel it was beneficial as a prophylactic.^119,120

In artificial stimulation of the vestibular system ginger reduced the symptoms of vertigo but it did not prevent nystagmus.^85,121

Across these anti-emetic studies of varying aetiology results have been somewhat variable, but reviewers have, in the main, concluded that ginger is both effective and safe.^122–128

Cancer

Anti-oxidant and anti-inflammatory agents are believed to help prevent the development of cancer and ginger has shown good activity in both of these areas.^49,51,76

In vitro—In addition ginger and/or its constituents inhibit the growth of a number of cancer cell lines including some that have become drug-resistant (DR). Those found to be susceptible include ovary,129 colorectal,¹³⁰ prostate,¹³¹ breast,^132,133 gastric,¹³⁴ laryngeal,¹³⁵ liver (DR),¹³⁶ pancreas (DR),¹³⁷ leukaemia,^51,138,139 oral squamous¹⁴⁰ and lung.¹⁴¹

The mechanism of direct anticancer activity is multi-factorial, occurring through a variety of biochemical pathways, and includes enhanced apoptosis,^{132–135,138,140,141} cell cycle arrest^{130,133,134,137,142} and chemoprevention.^{131,143–146} The extract and/or constituents may also have some benefit in halting metastatic spread of the disease by modulating angiogenesis^129,142,147 and reducing cell motility and adhesion.¹³³

[6]-gingerol increases the uptake of chemotherapeutic agents in cancer cells which have become drug resistant by increasing their transport into cells using P-glycoprotein.¹⁴⁸

In vivo—There are no trials using ginger in cancer treatment however a diet rich in phenolics is linked epidemiologically with a lower risk of cancer development and ginger contains a high proportion of these constituents.¹⁴⁹

Circulation

Although ginger is a traditional herb for stimulating circulation there is an absence of relevant research in humans into possible mechanisms.

In vitro—Zingiber protected endothelial cells from monocyte adhesion, a process involved in inflammation and atheroma formation.¹⁵⁰ Many of the arylalkanone constituents and ginger itself have strong antiplatelet activity through inhibition of arachidonic acid metabolism to thromboxane, prostaglandin and prostaglandin-endoperoxides in platelets.^{61,151,152,220}

In vivo—Heart disease is related to arterial inflammation which occurs via arachidonic acid metabolism and ginger could therefore be beneficial.¹⁵³

Studies have been mainly concerned with the effect of the herb on platelet activity and they have not been conclusive. Concomitant consumption of fat and 5 g of ginger in normal healthy people countered the decreased fibrinolytic activity which occurred with fat intake alone^154,155 and a single dose of 10 g¹⁵⁶ or 5 g ginger daily for a week¹⁵⁷ inhibited platelet aggregation. There is also an anecdotal account of a patient with a high platelet count being given ginger powder with beneficial results.¹⁵⁸

However, regular daily ginger at a lower dose (4 g), taken over three months, did not affect platelet aggregation, fibrinolytic activity, fibrinogen or lipid levels in coronary artery disease patients¹⁵⁶ and in young healthy adults 15 g raw or 40 g of cooked ginger daily for 2 weeks did not significantly change their thromboxane levels.¹⁵⁹

Although the herb has a traditional use in the Indian sub-continent for the treatment of hypertension there are no studies reporting the effect of ginger on blood pressure.

Antimicrobial

In vitro—A range of antimicrobial activity has been shown for the extract and/or the essential oil including:-

• virucidal for HSV-1,¹⁶⁰ HSV-2,¹⁶¹ rhinovirus 1B¹⁶² and hepatitis C virus¹⁶³
• antibacterial to Staphylococcus aureus, Bacillus cereus, B.subtilis, Listeria monocytogenes, Proteus mirabilis, Vibrio parahaemolyticus, Pseudomonas aeruginosa, Escherichia coli, Salmonella typhimurium, Streptococcus pyogenes, S. pneumoniae, Haemophilus influenzae, Campylobacter jejuni^164–172 and as many as 19 strains of Helicobacter pylori.^21,173–177 In addition ginger and [10]-gingerol can act synergistically with some antibiotics against resistant strains of bacteria^166,173,178
• antimycobacterial including against Mycobacterium tuberculosis¹⁷⁹
• antifungal including against Candida albicans, Aspergillus niger, Cryptococcus neoformans and Trichophyton mentagrophytes^170,180,181
• antiparasitic against Schistosoma mansoni (although the in vivo activity is uncertain)^182,183 and against the larvae of the fish borne nematode Anisakis¹⁸⁴
• molluscicidal against the snail vector of Schistosoma transmission¹⁸³

Other

In vitro—Other activities that have been established for ginger and/or its constituents include:

• a unique specificity of the proteases which are more effective than papain23
• good inhibition of the enzyme aldose reductase which may play a part in the tissue damage caused by diabetes¹⁸⁵
• protection of neurones from the effect of β-amyloid, the protein implicated in Alzheimer's disease¹⁸⁶
• some phyto-oestrogenic activity¹⁸⁷
• stimulation of TRPA1 receptors which perceive a burning sensation and are activated by the inflammatory peptide bradykinin¹⁸⁸
• immuno-suppressive activity reducing lymphocyte proliferation via decreased production of cytokines but the significance of this in vivo is uncertain¹⁸⁹
• potential as a protective agent against ulcers, gastritis and gastric cancer associated with bacterial infection¹⁷⁷

In vivo—Zingerone appears to be a nerve irritant that on repeated exposure causes desensitization to oral trigeminal nerve chemoreceptors, a pattern of perception that is qualitatively similar to but milder than capsaicin.^190,191

Zingiber reduces artificially-induced stress responses in healthy volunteers as measured by ACTH and cortisol levels.¹⁹² Other in vivo studies have shown:-

• in spite of its reputation as an antidiabetic herb in some traditions ginger taken daily for 3 months did not reduce blood sugar in patients with coronary artery disease.¹⁵⁶ However GI dysrhythmia in healthy volunteers due to hyperglycaemia was reduced by it, through reduced endogenous prostaglandin synthesis, and the herb may therefore reduce gastro-intestinal discomfort normally experienced by diabetics¹⁹³
• a combined preparation of feverfew and ginger was an effective treatment for migraine headaches when taken in the mild phase¹⁹⁴
• ginger, as part of a Japanese herbal combination, reduced levels of Immunoglobulin E in the sera of sufferers of refractory atopic dermatitis^195,196
• a herbal combination which included Zingiber as well as gallic acid was ineffective in reducing body weight and food intake in healthy overweight people.^197,198 Unlike Capsicum, Zingiber has not been shown to increase postprandial metabolic rate¹⁹⁸

Inconsistencies in pharmacological activity and clinical outcomes of ginger could be attributed to variability in both manufactured and raw ginger products,^12,43 dosage/dosage-regime differences and lack of a standardised test product. Gingerol content for example was found to vary widely amongst manufactured ginger products.^12,199 Standardisation of ginger however would present problems as there are so many active constituents.

Medicinal uses

Cardiovascular system

• cold extremities
• poor peripheral circulation

Respiratory tract

Some of the volatile oil components appear to be excreted through the lungs and would have an effect on:

• bronchitis
• common cold

Gastro-intestinal tract

• nausea and vomiting
• flatulence
• colic
• anorexia
• atonic dyspepsia especially in the elderly

Taken prophylactically it may help nausea induced by chemotherapy.

Reproductive tract

• dysmenorrhoea
• amenorrhoea

Musculoskeletal

• arthritis
• rheumatism

Pharmacy

Three times daily
Infusion of dried powdered	–   0.25–1 g rhizome
Infusion of fresh herb (grated)	–   0.3–3 g
Weak Tincture BP (1973)	–   1.5–3 ml
Strong Tincture BP (1973)	–   0.25–0.5 ml

The 1:5 tincture is referred to as “Weak” and the 1:2 as “Strong” ginger tincture. 70% ethanol content has been determined as the most effective extracting medium.200

As an anti-emetic effective doses have ranged from the equivalent of 1–6 g powdered rhizome daily. In the study on prevention of seasickness 500 mg gave 4 hours of protection.¹¹⁹

Precautions and/or safety

Safety data on the herb indicate that it is safe to use in pregnancy.^95,98,201 In general ginger appears to be safe even at doses of up to 6 g daily.¹²⁴ Some studies have monitored the effects of its continuous use over 2.5 years and found no serious side effects.⁷⁷

Standard in vitro assays showed ginger is not genotoxic²⁰² and actually protects DNA from damage by known carcinogens.^203,204 However there are contradictory reports on both its mutagenic and anti-mutagenic potential.^205–208

Reported side-effects are rare and minor and include mild gastro-intestinal symptoms—heartburn, nausea, flatulence, mild diarrhoea—and also sleepiness.^81,124 Although uncommon it is possible some people may develop contact dermatitis from handling ginger^209,210 or asthma from inhalation of its dust.²¹¹

Ginger is assumed to increase bleeding due to its antiplatelet activity. In vivo doses of up to 4 g of the herb taken daily for 3 months did not alter any of the factors associated with platelet function.^156,212

Consumption of more than 6 g of ginger as a single dose may be associated with increased sloughing of gastric epithelial cells.²¹³

Interactions

In vitro—The increased uptake of chemotherapeutic drugs and their reduced transport out of cancer cells by P-glycoprotein has raised the possibility of a potential interaction between ginger and drugs transported in this way.¹⁴⁸

The ginger/galangal combination modulates the expression of CYP1A2 and CYP3A4 and the transporter protein MDR1.²¹⁴

In vivo—[6]-gingerol was estimated to be twoto four-fold less active than aspirin in terms of its effect on inhibiting platelet aggregation.²¹⁵ An increased risk of bleeding in patients who use ginger whilst taking warfarin is generally expected²¹⁶ however a study of healthy subjects taking a single dose of warfarin and ginger together found no interaction in terms of pharmacokinetics (metabolism) or pharmacodynamics (physiological effects).^217,218 A literature search failed to find evidence of interactions.²¹⁹

Ginger (1 gm daily) used with nifedipine in normal and hypertensive patients synergistically inhibited platelet aggregation in a manner similar to low dose aspirin (75 mg daily).²²⁰

There is one report in the literature of an interaction between phenprocoumon and ginger in an elderly patient resulting in a raised INR and epistaxis.²²¹

Historical uses

The herb has a long history of use in China. The fresh rhizome is used to treat vomiting; coughs; abdominal distension and pyrexia. The dried rhizome for abdominal pain; lumbago and diarrhoea. Also used for alcoholic gastritis; diarrhoea due to relaxed bowel. Hot infusion for restarting menstruation halted due to cold. Also for cataracts, toothache, insomnia, baldness, haemorrhoids and to increase longevity.