Ginger: Background. Actions

2010

Historical Note

Ginger has been used as both a food and a medicine since ancient times. Confucius wrote about it in his Analects, the Greek physician, Dioscorides, listed ginger as an antidote to poisoning, as a digestive, and as being warming to the stomach in De Materia Medica, and the Koran, the Talmud and the Bible all mention ginger. Records suggest that ginger was highly valued as an article of trade and in 13th and 14th century England, one pound of ginger was worth the same as a sheep. Ginger is still extremely popular in the practice of phytotherapy, particularly in TCM, which distinguishes between the dried and fresh root. It is widely used to stimulate circulation, treat various gastrointestinal disorders and as a stimulant heating agent.

Other Names

African ginger, Indian ginger, Jamaica ginger, common ginger, rhizoma zingiberis, shokyo (Japanese)

Botanical Name / Family

Zingiber officinale Roscoe (family Zingiberaceae)

Plant Part Used

Rhizome

Chemical Components

The ginger rhizome contains an essential oil and resin known collectively as oleoresin. The composition of the essential oil varies according to the geographical origin, but the chief constituents, sesquiterpene hydrocarbons, which are responsible for the characteristic aroma, are fairly constant.

The oleoresin contains:

• sesquiterpenes: zingiberene, ar-curcumene, beta-sesquiphellandrene and beta-bisabolene

• pungent phenolic compounds: gingerols and their corresponding degradation products, shogaols, zingerone, and paradol. Zingerone and shogaols are found in small amounts in fresh ginger and in larger amounts in dried or extracted products

• other constituents: diarylheptanoids galanolactone (diterpenoid), 6-gingesulfonic acid), monoacyldigalactosylglycerols.

Main Actions

ANTI-EMETIC

Ginger has demonstrated anti-emetic activity in both experimental models and human studies, the exact mechanism of which is still unknown although both shogaols and gingerols have been shown to have anti-emetic activity.

It appears that several key constituents and several different mechanisms are responsible. According to both animal and human studies, ginger reduces emesis due to a peripherally acting mechanism, acting on the gastrointestinal tract alone. One constituent found in ginger, galanolactone, is a serotonin receptor antagonist, which may partly explain the anti-emetic effect. It also explains the inhibitory effect of ginger on serotonin-induced diarrhea and antispasmodic effects on visceral and vascular smooth muscle.

Ginger has been shown to blunt gastric dysrhythmias and nausea evoked by acute hyperglycaemia in humans. The anti-arrhythmic and anti-emetic effects are thought to be due to a blockade of prostaglandins rather than inhibition of their release. Ginger has also been shown to reduce radiation-induced gastrointestinal distress and emesis in rat models, which is thought to be due at least in part to its antioxidant properties and the ability to scavenge free radicals and inhibit lipid peroxidation.

GASTROINTESTINAL ACTIVITY

Ginger exerts several effects in the gastrointestinal tract. It stimulates the flow of saliva, bile and gastric secretions and has been shown to increase gastrointestinal motility without affecting gastric emptying in several animal models and human studies. Ginger has also been observed to have prokinetic activity in mice in vivo and antispasmodic activity in vitro. These findings appear to support the traditional use of ginger in the treatment of gastrointestinal discomfort, colic, diarrhea and bloating and its use as a carminative agent.

Anti-ulcer activity

A number of in vivo studies have identified antiulcer activity for ginger extract and several of its isolated constituents. The orally administered acetone extract of ginger at a dose of 1000 mg/kg and zingiberene, the main terpenoid in this extract, at 100 mg/kg significantly inhibited gastric lesions by 97.5% and 53.6%, respectively. Additionally, the pungent principle, 6-gingerol at 100 mg/kg, significantly inhibited gastric lesions by 54.5%. These results suggest that both zingiberene and 6-gingerol are important constituents responsible for ginger’s anti-ulcer activity. Other constituents demonstrating antiulcer properties in gastric ulcer models in rats include beta-sesquiphellandrene, beta-bisabolene, ar-curcumene and shogaol.

In addition to direct anti-ulcer activity, ginger exerts synergistic effects with the antibiotic clarithromycin in inhibiting different Helicobacter pylori isolates independent of the organisms’ susceptibility to clarithromycin.

HYPOLIPIDAEMIC

High doses of an aqueous extract of ginger (500 mg/kg) significantly reduced serum cholesterol according to an animal study that used oral doses of a raw aqueous extract of ginger administered daily for a period of 4 weeks.

Effects on triglyceride levels are more difficult to determine, as one study demonstrated that 250 µg ginger extract/day reduced serum triglyceride levels by 27% in mice, whereas another study using a high dose of 500 mg/kg found no significant effects.

An ex-vivo study found that 250 µg/day of a standardised ginger extract significantly reduced plasma LDL-cholesterol levels, the LDL basal oxidative state, as well as LDL-cholesterol and serum cholesterol’s susceptibility to oxidation and aggregation, compared with placebo. Ginger also reduced aortic atherosclerotic lesions by 44% in atherosclerotic mouse aorta.

ANTI-INFLAMMATORY AND ANALGESIC

The anti-inflammatory effects of ginger may be due to its effects on the arachidonic acid cascade, as COX-1 and -2 and lipoxygenase inhibition has been shown in vitro and high oral doses of an aqueous extract of ginger (500 mg/kg) significantly lowered serum PGE2 and thromboxane B2 levels in rats.

Ginger also suppresses leukotriene biosynthesis by inhibiting 5-lipoxygenase, thus distinguishing ginger from NSAIDs. Additionally, ginger extract has been shown to inhibit thromboxane synthase and a ginger extract (EV.EXT.77) has been found to inhibit the induction of several genes involved in the inflammatory response. These include genes encoding cytokines, chemokines, and the inducible enzyme COX-2, thus providing evidence that ginger modulates biochemical pathways activated in chronic inflammation.

No one single constituent seems to be responsible for the anti-inflammatory effect of ginger. An acetone extract containing gingerols, shogaols and minor compounds like gingerenone A, [6]-gingerdiol, hexahydrocurcumin and zingerone have been shown synergistically to produce dose-dependent anti-inflammatory effects. Other studies have identified the gingerols and diarylheptanoids and gingerdione as the key compounds responsible.

Gingerol and 8-gingerol have been found to evoke capsaicin-like intracellular Ca2+ transients and ion currents in vitro and it has been suggested that gingerols represent a novel class of naturally occurring vanilloid receptor agonists that contribute to ginger’s medicinal properties. This is supported by the finding that topical application of ginger creams or compresses produce an analgesic capsaicin-like effect on the release of the immunoreactive substance P from primary afferent neurons. In an animal study of chemically induced inflammation, ginger extract reduced oedema that was partly caused by serotonin-receptor antagonism. Additionally, ginger oil has shown anti-inflammatory activity, significantly suppressing both paw and joint swelling in severe adjuvant arthritis in rats.

ANTIPLATELET

It has been suggested that gingerols and their derivatives represent a potential new class of platelet activation inhibitors, with synthetic gingerols being found to inhibit the arachidonic acid-induced platelet release reaction in vitro in a similar dose range as aspirin possibly due to an effect on COX activity in platelets.

Powdered ginger exerted an antiplatelet activity when taken in very high doses of at least 10 g, according to one human study. A randomised double-blind study found that doses up to 2 g of dried ginger had no effect on bleeding time, platelet aggregation or platelet count. This lack of effect has been demonstrated in healthy volunteers and those with type 1 diabetes mellitus or coronary artery disease.

ANTIMICROBIAL AND ANTIPARASITIC

Ginger extract and several of its main constituents exhibit antimicrobial activity in vitro and in vivo. Ginger extract has been shown to have an antibacterial effect against Staphylococcus aureus, Streptococcus pyogenes, S. pneumoniaeand Haemophilus collected from throat swaps of infected individuals. The minimum inhibitory concentration of ginger ranged from 0.0003-0.7 µg/mL, and the minimum bactericidal concentration ranged from 0.135-2.04 µg/mL. Ginger has also shown antischistosomal activity. Gingerol (5.0 ppm) completely abolished the infectivity of Schistosoma spp. (blood flukes) in animal studies. Gingerol and shogaol exhibited potent molluscicidal activity in vivo.

Gingerols demonstrated antibacterial activity against Bacillus subtilis and Escherichia coll in vitro, and the essential oils of ginger have been shown to have antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts and filamentous fungi in vitro. Shogaol and gingerol have demonstrated anti-nematode activities; 6.25 µg/mL 6-shogaol destroyed Anisakis larvae within 16 hours in vitro, whereas the antinematodal medication pyrantel pamoate had no lethal effect at 1 mg/mL. Ginger constituents have also been shown to be antifungal and antiviral. Shogaol and zingerone strongly inhibited Salmonella typhi, Vibrio choleraeand Tricophyton violaceum. Aqueous extracts have also been shown to be effective against Trichomonas vaginalis. Several sesquiterpenes, but especially beta-sesquiphellandrene, isolated from ginger have also been shown to have antirhinoviral activity in vitro.

ANTIOXIDANT

According to in vivo research, ginger exerts significant direct and indirect antioxidant effects. Orally administered ginger significantly lowered levels of free radicals and raised the activities of endogenous antioxidants superoxide dismutase and catalase and had a sparing effect on vitamins C and E.

IMMUNOMODULA TION

In vitro and in vivo research suggests ginger extract exerts some degree of immunomodulatory activity and has been shown to significantly prolong the survival of cardiac allog rafts in mice. Ginger oil has also been shown to have immunomodulatory activity in mice, with dose-dependent inhibition of T lymphocyte proliferation and IL-1 -alpha secretion in vitro and reduced delayed type of hypersensitivity response in vivo.

HEPATOPROTECTIVE

Ginger has significant hepatoprotective effects comparable to those of silymarin, according to research with experimental models of alcohol-induced liver damage.

Other Actions

ANTIHISTAMINE

Shogaols and certain gingerols exhibit dose-dependent inhibition of drug-induced histamine release from rat peritoneal mast cells in vitro.

ANXIOLYTIC

A combination of ginger and Ginkgo biloba has been shown to reduce anxiety in an animal model (elevated plus-maze test). The effect was similar to diazepam. A highly non-polar fraction of a ginger extract has been shown to possess anticonvulsant, anxiolytic and anti-emetic activities in animals.

ANTIFIBROTIC

Supplementation with 5 g ginger not only prevented a decrease, but also significantly increased fibrinolytic activity in 30 healthy adult volunteers who consumed 50 g fat in a meal in an open clinical study.

APOPTOSIS

A pungent phenolic substance found in ginger (6-paradol) effectively inhibits tumour promotion in mouse skin carcinogenesis. 6-Paradol and structurally related derivatives have also been shown to induce apoptosis through a caspase-3-dependent mechanism (caspase is a ‘suicidal’ cell protein that, when activated, induces the cell to destroy itself).

POSITIVE INOTROPE

Gingerols and shogaols isolated from ginger have positive inotropic activity, as demonstrated on isolated heart muscle. The effect of gingerol seems to be rather specific to SR Ca2+-ATPase activity.

THERMOGENIC

Ginger helps to maintain body temperature and inhibit serotonin-induced hypothermia in vivo. However, the addition of a ginger-based sauce to a meal did not produce any significant effect on metabolic rate in humans.