a review of the gastroprotective effects of ginger (zingiber officinale roscoe)

Food & Function

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View Article OnlineView Journal | View Issue

A review of the ga

aDepartment of Research, Research and

College, Kankanady, Mangalore, Karnatak

gmail.com; Fax: +91-824-2437402; +91-824bDepartment of General Surgery, Father

Mangalore, Karnataka, India 575002

DpDCPEdgMwDrp

effects of ginger. Dr Haniadka is a refellowship (STS 2008) from the Indand has published four text bookinternational journals of repute.

Cite this: Food Funct., 2013, 4, 845

Received 26th November 2012Accepted 15th March 2013

DOI: 10.1039/c3fo30337c

www.rsc.org/foodfunction

This journal is ª The Royal Society of

stroprotective effects of ginger(Zingiber officinale Roscoe)

Raghavendra Haniadka,a Elroy Saldanha,b Venkatesh Sunita,a Princy L. Palatty,c

Raja Fayadd and Manjeshwar Shrinath Baliga*a

The rhizomes ofZingiber officinaleRoscoe (Zingiberaceae), commonly knownas ginger is an important kitchen

spice and also possess a myriad health benefits. The rhizomes have been used since antiquity in the various

traditional systems of medicine to treat arthritis, rheumatism, sprains, muscular aches, pains, sore throats,

cramps, hypertension, dementia, fever, infectious diseases, catarrh, nervous diseases, gingivitis, toothache,

asthma, stroke and diabetes. Ginger is also used as home remedy and is of immense value in treating various

gastric ailments like constipation, dyspepsia, belching, bloating, gastritis, epigastric discomfort, gastric

ulcerations, indigestion, nausea and vomiting and scientific studies have validated the ethnomedicinal uses.

Ginger is also shown to be effective in preventing gastric ulcers induced by nonsteroidal anti-inflammatory

drugs [NSAIDs like indomethacin, aspirin], reserpine, ethanol, stress (hypothermic and swimming), acetic acid

and Helicobacter pylori-induced gastric ulcerations in laboratory animals. Various preclinical and clinical

studies have also shown ginger to possess anti-emetic effects against different emetogenic stimuli. However,

conflicting reports especially in the prevention of chemotherapy-induced nausea and vomiting and motion

sickness prevent us from drawing any firm conclusion on its effectiveness as a broad spectrum anti-emetic.

Ginger has been shown to possess free radical scavenging, antioxidant; inhibition of lipid peroxidation

and that these properties might have contributed to the observed gastroprotective effects. This review

summarizes the various gastroprotective effects of ginger and also emphasizes on aspects that warranty

future research to establish its activity and utility as a gastroprotective agent in humans.

Development, Father Muller Medical

a, India 575002. E-mail: msbaliga@

-2436352; Tel: +91-824-2238331

Muller Medical College, Kankanady,

cDepartment of Pharmacology, Father Muller Medical College, Kankanady,

Mangalore, Karnataka, India 575002dDepartment of Exercise Science, Arnold School of Public Health, University of South

Carolina, Columbia, SC 29208, USA

r Raghavendra Haniadka is aostgraduate student in theepartment of Anesthesiology &ritical Care at the prestigiousostgraduate Institute of Medicalducation and Research, Chan-igarh, India. He did his under-raduate degree in Father Mulleredical College Mangalore andorked as a student assistant tor MS Baliga on the mechanismsesponsible for the chemo-reventive and chemoprotectivecipient of the prestigious researchian Council of Medical Researchchapters and seven papers in

Dr Elroy Saldanha is a currentpostgraduate student in theDepartment of General Surgeryat Father Muller MedicalCollege and is working as asenior student assistant to DrsPL Palatty and Baliga. He isrecipient of the prestigiousresearch fellowship (STS 2005)from the Indian Council ofMedical Research and workedunder the mentoring of Dr Pal-atty. Dr Saldanha's interests are

in the area of gastric surgery and have published three papers ininternational journals of repute.

Chemistry 2013 Food Funct., 2013, 4, 845–855 | 845

http://dx.doi.org/10.1039/C3FO30337C

http://pubs.rsc.org/en/journals/journal/FO

http://pubs.rsc.org/en/journals/journal/FO?issueid=FO004006

Food & Function Review

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. View Article Online

1 Introduction

The stomach, the muscular, hollow, dilated part locatedbetween the esophagus and the small intestine of the alimen-tary canal, is a vital organ functioning under the control of theneuro-hormonal system. The principal function of the stomachis to secrete proteolytic enzymes and powerful acids to ensurethe chemical digestion of macerated food (bolus) that hasarrived from the oral cavity and to then send the partiallydigested food (chyme) to the small intestine for further diges-tion and absorption, thereby making it an important organ forsustenance and healthy living for the individual.1 The stomachis a sensitive organ and may be affected by various factors bothof endogenous and exogenous origins. Ailments like dyspepsia,belching, bloating, gastritis and epigastric discomfort areconsidered to be mild, while gastric ulcers and cancer causesevere morbidity and mortality.1 A number of pharmaceuticaldrugs are available for the treatment of various gastric ailments/

Ms Sunitha Venkatesh is a nalyear medical undergraduatestudent in Father MullerMedical College and is workingas a student assistant to DrBaliga. She is the recipient of theprestigious research fellowship(STS 2012) from the IndianCouncil of Medical Research andworked under the mentoring ofDr Baliga.

Dr Princy L Palatty is a professorin the Department of Pharma-cology at Muller MedicalCollege. She has over twentyyears of experience in clinicaland experimental pharma-cology. She is a recognised guidefor the MD curriculum and hasbeen an examiner for bothundergraduate and post-graduate courses in the medicalcurriculum. She has been aprincipal investigator in

national projects and has published over 25 publications in peerreviewed journals and text books. Currently she is the chair personof the prestigious UNESCO BIOETHICS unit of South India.

846 | Food Funct., 2013, 4, 845–855

diseases, but their repeated use is associated with untowardside effects and negates the therapeutic benet.1 In view ofthese observations the need for agents that are both effectiveand devoid of side effects are required.

2 The kitchen spice ginger as agastroprotective agent

Dietary agents have been a source of medicine and the rhizomesof Zingiber officinale, colloquially known as ginger is arguablythe most important gastroprotective agent in the varioustraditional systems of medicine.2 Ginger belongs to the familyZingiberaceae and is supposed to be indigenous to South-EastAsia (today's Northeast India). However, today the plants arecultivated and found growing in many tropical and subtropicalregions of the world like Nigeria, Sierra Leone, Indonesia,Bangladesh, Australia, Fiji, Jamaica, Nepal, Haiti, Mexico andHawaii.3 The rhizomes are the most important part and are

Dr Raja Fayad is a medicaldoctor and a tenure-track assis-tant professor in the AppliedPhysiology Division at theUniversity of South Carolina.His background research is ingastroenterology and mucosalimmunology. Particularly, hisresearch is focused on chronicinammation induced coloncancer in adiponectin, a proteinproduced by fat cells, deciencystatus. He is a target PI at Colon

Cancer Center at the University of South Carolina and was a PI onseveral recently completed grants from the Crohn's and ColitisFoundation of America and Broad Foundation. He has publishedover 25 articles concerning inammation related diseases.

Dr Manjeshwar Shrinath Baligais a senior scientist at FatherMuller Medical College andHospital. He obtained his PhDfrom Manipal University, India,and postdoctoral training at theUniversity of Alabama at Bir-mingham, USA, and University ofIllinois at Chicago, USA. DrBaliga is a recipient of severalprominent fellowships includingthe Commonwealth to UK in1992 and Indian National

Academy of Sciences in 2008. He is a life member of numerousprofessional societies, editorial board member/reviewer of severalpeer-reviewed journals. He has been a principal investigator innational projects and has published over 70 publications in peerreviewed journals.

This journal is ª The Royal Society of Chemistry 2013


Table 1 The different vernacular names of ginger in India and other parts of theworld

Language Names

Scientic name Zingiber officinale RoscoeEnglish Ginger

Indian languagesAssamese AdaBengali AdaGujarati AduHindi AdrakKannada ShuntiKonkani Shunti, AlaeMalayalam InjiManipuri ShingMarathi AaleMizo ThingpuidumOriya AdaPali SingiveraPunjabi AdarakaSanskrit ArdrakaTamil InjiTelugu AllamUrdu Adrak

Other languagesArabic ZanjbeelBurmese SifDutch GemberFilipino LuyaFrench GingembreGerman IngwerItalian ZenzeroJavanese JaheKhmer KhnyyiMalay HaliaNepali Sano AdwaRussian ImbirSinhala InguruSpanish JengibreSwahili TangawiziThai KlngTibetan Sga skya

Review Food & Function

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used as both medicinal and culinary agent.3–5 The vernacularname of ginger in various Indian and other internationallanguages is enlisted in Table 1.

3 Phytochemistry of ginger

Ginger is one of the highly investigated dietary agents for itschemical constituents and studies have shown it to contain awide variety of volatile and non-volatile compounds, and alsothat their concentration varies with growing conditions,temperature, harvesting and processing.3–7 The characteristicaroma of ginger is credited to be due to the presence of volatilecompounds like camphene, b-phellandrene, curcumene,cineole, geranyl acetate, terphineol, terpenes, borneol, geraniol,limonene, b-elemene, zingiberol, linalool, a-zingiberene, b-sesquiphellandrene, b-bisabolene, zingiberenol and a-farm-esene.3–7 The non-volatile molecules like the gingerols,


shogaols, paradols and zingerone render pungency to gingerand are responsible for the warm pungent sensation in themouth.3,6,7 Fresh ginger also contains gingerols, a series ofchemical homologs differentiated by the length of theirunbranched alkyl chains; [3–6]-, [8]-, [10]-, and [12]-gingerolsand having a side-chain with 7–10, 12, 14, or 16 carbon atoms,respectively as the major active components. Of all the ginger-ols, the compound 6-gingerol is the most abundant.3–8 Ginger-ols are thermolabile and undergo dehydration to form thecorresponding shogaols rapidly. Shogaols may be further con-verted to paradols by hydrogenation.6,7 The other constituentspresent are neral, capsaicin, gingediol, galanolactone, ginge-sulfonic acid, galactosylglycerols, gingerglycolipids, diary-lheptanoids and phytosterols.5–7 Some of the chemicalstructures are represented in Fig. 1.

4 Traditional uses of ginger

For centuries, ginger has been extensively used as both medic-inal and dietary agent in Southeast Asia. It is a crucial ingre-dient in the various Chinese, Ayurvedic, Unani, Tibetan,Srilankan, Korean, Arabic, Greek, Roman and also in thevarious folk systems of medicines all over the world. In theAyurvedic system of medicine, ginger is called “maha aushadhi”,meaning the great medicine and is used to treat wide array ofailments. It also nds wide applications in other traditional andfolk systems of medicine (Table 2).3–7 Ginger has been an inte-gral ingredient for managing digestive disorders and has beenused as a carminative and digestive, and to prevent nausea andvomiting, motion sickness, stomach ache, stomach ulcers,bacterial dysentery and dyspepsia. In the following sectionthese aspects will be addressed in details.

5 Validate scientific studies5.1 Ginger prevents epigastric discomfort and dyspepsia

Ginger is a frontline dietary agent to possess carminative effectand offers relief by decreasing pressure on lower esophagus,reducing intestinal cramping, preventing dyspepsia, atulenceand bloating.4,5Clinical studies have shown that consumption ofginger enhances relaxation of the lower esophageal sphincter, todecrease esophageal contraction velocity, and that these activi-ties possibly mediate the anti-atulent effects of ginger.9 Addi-tionally, double blind studies carried out in patients withfunctional dyspepsia have also shown that, when compared tothe patients whohave had received placebo, the gastric emptyingwas more rapid in the cohorts that had received ginger.10 Ultra-sound studies at frequent intervals post ginger consumption hasshowed that therewas a trend formore antral contractions,whileno alterations were observed in the fundus dimensions orgastrointestinal symptoms, and also in the concentrations of thegut peptides GLP-1, motilin and ghrelin in the serum.10

5.2 Ginger protects against cisplatin and pyrogallol-induceddelay in gastric emptying

Cisplatin and pyrogallol causes severe nausea and vomiting,accompanying gastrointestinal symptoms such as abdominal

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Fig. 1 Important phytochemicals present in ginger.


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discomfort and delay in gastric emptying time.11–13 Labora-tory studies with rats have shown that the oral pretreatmentwith acetone and 50% ethanolic extract of ginger (100, 200and 500 mg kg�1) and ginger juice (2 and 4 ml kg�1)reversed cisplatin-induced delay in gastric emptying.12

Additionally studies have also shown that the acetone extractof ginger (100, 250 and 500 mg kg�1) reversed the pyrogallol-induced delay in gastric emptying.13 Together, all theseobservations clearly indicate the potential of ginger inimproving symptoms such as abdominal discomfort, bloat-ing and emesis.13

5.3 Ginger is an effective anti-emetic agent

Ginger has been used as an anti-emetic agent in various tradi-tional systems of medicine since antiquity and scientic studieshave shown ginger to be efficacious in preventing nausea andvomiting in various conditions.3–8,14 Ginger is shown to beeffective in ameliorating nausea and vomiting during earlypregnancy15–19 and without increasing pregnancy-relatedcomplications, the pregnancy outcome and congenital abnor-malities.18,20 Ginger is also reported to prevent post-operativenausea and vomiting.21–23 Preclinical studies with experimental

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animals have also shown that ginger juice produces antimotionsickness action, and that this action was possibly due to itseffect on the central and peripheral cholinergic, histaminergicand serotonergic pathways.24 However, human studies haveshown divergent results with certain reports indicating it to bebenecial,25,26 while others were contradicting the usefulness.27

However studies have equivocally shown ginger to be effectivein reducing the sea sickness in human volunteers and navalcadets indicating its usefulness in maritime endeavors andwork.28,29

Ginger is also shown to be effective in preventing radio-therapy and chemotherapy-induced nausea and vomiting.Seminal studies by Arora and co investigators30,31 have shownthat the intraperitoneal administration of the hydroalcoholicextract of ginger one hour before exposure to 2 Gy of g irradi-ation was effective in blocking the saccharin avoidanceresponse. The optimal effective dose was observed to be 200 mgkg�1 b wt in males,29 and 250 mg kg�1 in female rats31 respec-tively. Ginger is also shown to be effective in preventingcisplatin-induced emesis in the healthy mongrel dogs. Theacetone extract was more valuable than the ethanolic extract butwas less effective than granisetron.32 The acetone, 50% etha-nolic extract and fresh ginger juice were also effective in



Table 2 Traditional uses of ginger rhizome in different countries3–6

Country Pharmacological property

Arabian nations Aphrodisiac, anti-emetic, stomachic, carminative;cold, headaches, nausea, stomach upset, motionsickness and morning sickness, diarrhea, helpdigestion, treat arthritis, rheumatologicalconditions, muscular discomfort, carminative andanti-atulence

Burma Anti-u agent, anti-emetic, rheumatologicalconditions, carminative, cold, nausea, motionsickness and morning sickness and stomach upset

China anti-emetic, antitussive, expectorant, diaphoretic,antihypertensive, arthritis, rheumatologicalconditions, muscular discomfort, motion sicknessand morning sickness, carminative and antiatulent

Congo Against common cold, anti-emetic, arthritis,rheumatological conditions, carminative,antiatulent, cold, nausea and stomach upset

Europe anti-emetic, digestive aid, carminative, antiatulent,cold, nausea

Germany anti-emetic, digestive aid, preventing motionsickness

Greece Digestive aid, anti-emetic, rheumatologicalconditions, motion sickness and morning sickness

India Antispasmodic, antiinammatory, anti-emetic,aphrodisiac, astringent, digestive aid, motionsickness and morning sickness. Antithrombotic andantiarthritic

Indonesia Improving fatigue, antihypertensive, digestive aid,antirheumatic, carminative, antiatulent, cold,nausea

Japan anti-emetic, antitussive, expectorant, diaphoretic,carminative, antiatulent, cold, nausea

Srilanka Carminative, diaphoretic, antispasmodic,expectorant, peripheral circulatory stimulant,astringent, appetite stimulant, anti-inammatoryagent, diuretic and digestive aid

Tibetan Carminative, diaphoretic, antispasmodic,expectorant, peripheral circulatory stimulant,astringent, appetite stimulant, anti-inammatoryagent, diuretic and digestive aid

United States ofAmerica

Carminative, stomachic, antispasmodic,diaphoretic, against motion sickness and morningsickness


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preventing cisplatin-induced delayed gastric emptying in rats.32

The reversal produced by ginger juice was better than the 5-HT3receptor antagonist ondansetron, while that of the acetoneextract was similar to it.12

Gingerol, the active principle of raw ginger, was alsoreported to possess anti-emetic property against cisplatinand the effect was similar to that of ondansetron, used aspositive control.33 Mechanistic studies suggest that gingerolcaused a dose-dependent suppression in the levels ofsubstance P and NK1 receptors in the area postrema andileum and suggest its action to be similar to that of apre-pitant.33 Additionally, studies have also shown that [6]-, [8]-and [10]-gingerol and [6]-shogaol exert their anti-emeticeffect at least in part by acting on the 5-HT(3) receptor ion–channel complex, probably by binding to a modulatory sitedistinct from the serotonin binding site. This may include


indirect effects via receptors in the signal cascade behind the5-HT(3) receptor channel complex such as substance Preceptors and muscarinic receptors.34 The activity can besummarized as 5-HT(3) antagonist, NKI antagonist, antihis-taminic and prokinetic effects, and was devoid of anyadverse effects.

Although ginger was effective in preventing chemotherapy-induced nausea in animals, the clinical observations havebeen contradictory. Double-blinded crossover studies withgynecologic cancer patients receiving cisplatin have shownthat ginger when combined with standard anti-emeticregimen was ineffective in reducing chemotherapy-inducednausea and vomiting in the acute phase of cisplatin-inducedemesis, while it was as effective in the delayed phase and theeffect was similar to that of the conventionally used meto-clopramide.35 Subsequent studies have shown it to be effec-tive in reducing CINV stimulated by cyclophosphamidecontaining anticancer drug regimens, with the effect beingequal to that of metoclopramide but inferior to ondanse-tron.36 Additionally combining high protein meals with gingeris also shown to reduce the chemotherapy-induced delayednausea and the use of standard anti-emetic medications incancer patients.37

Series of reports published in the recent past have alsoshown that combining the conventionally used anti-emetics the5-HT(3) receptor antagonists and dexamethasone with gingeroffered better effects in reducing the CINV in children andyoung adults being treated for sarcoma of the bone38 andwomen for breast cancer.39 Additionally, ginger supplementa-tion at a daily dose of 0.5–1.0 g along with 5-HT(3) receptorantagonist anti-emetic on day 1 of all cycles is also shown toreduce the severity of acute chemotherapy-induced nausea inadult cancer patients indicating its usefulness.40 However, theobservations of Zick et al.,41 contradict the previous reports andindicate that ginger offers no benecial effects in reducing theprevalence or severity of acute or delayed CINV when combinedwith 5-HT3 receptor antagonists and/or aprepitant. Addition-ally, the authors also reported that the cohorts receiving bothginger and aprepitant had more severe acute nausea thanparticipants on aprepitant only suggesting a possibleantagonism.41

5.4 Ginger prevents gastric ulcerations

Gastric ulcers are one of the most important causes of humanmorbidity and ginger has been shown to offer benecial effectsagainst ulcerogens. In the following sections the gastro-protective effects of ginger against various stresses will beaccordingly addressed.

5.4.1 Ginger protects against indomethacin-induced ulcerin rat. Prolonged consumption of high doses of the analgesicindomethacin, causes gastric ulcers by generating free radicals,inhibiting prostaglandin synthesis and increasing the expres-sion of IL-1 and TNF-a.8,38,42 Preclinical studies have shown thatoral administration of 500 mg kg�1 ginger extract producedsignicant anti-ulcerogenic activity in rats subjected to indo-methacin administration.43

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5.4.2 Ginger protects against aspirin-induced ulcer in rat.Aspirin, a nonselective cyclooxygenase inhibitor is one of themost commonly used analgesic-antipyretic in clinics. Thechronic use of aspirin causes mucosal damage by interferingwith prostaglandin synthesis, increasing acid secretion andback diffusion of H+ ions.44 Experiments have shown that oraladministration of ginger oil (0.5 and 1 g kg�1) amelioratesaspirin alone and aspirin plus pylorus ligation-induced gastriculceration in rats by decreasing gastric acid secretion andincrease in mucus wall thickness.45

5.4.3 Ginger protects against reserpine-induced ulcer inrat. Reserpine is a potent gastric ulcerogen and causes gastriculcerations by generating free radicals, inhibiting mucusrelease and triggering the breakdown of surface mucus bystimulating b-adrenoceptor.46,47 Preclinical studies have shownthat pretreatment with 500 mg kg�1 of ginger extract pre-vented the occurrence of reserpine-induced gastriculceration.45

5.4.4 Ginger protects against hypothermic restraint stress-induced ulcer in rat. Hypothermic restraint is physical form ofstress and causes mucosal erosion and peptic ulcer At a cellularlevel hypothermic restraint stress causes generation of freeradicals, lipid peroxidation, alteration in the levels of prosta-glandin and histamine release, disturbances of gastric mucosalcirculation and abnormal gastric motility,48 and alteration ofgastric secretion,49 all of which have been shown to contributetowards stress-induced gastric mucosal damage and depletionof gastric mucus. Animal studies have shown that pretreatmentwith 500 mg kg�1 of ginger extract signicantly inhibited thegastric juice secretion and thus prevented the occurrence ofulcer caused by hypothermic restraint stress.43

5.4.5 Ginger protects against pyloric ligation-inducedgastric ulcer in rat. Pyloric ligation-induced model of gastriculceration is an important preclinical model study. The lesionsare induced through histamine-2 receptors (H2R), by triggeringthe secretion of acid (HCl) into the stomach lumen through thecAMP/protein kinase pathway.50,51 Studies with rats have shownthat the pretreatment with ginger extract (500 mg kg�1)decreases gastric acid secretion and to inhibit ulcer formation.43

Additionally, studies have also shown that ginger oil (0.5 and 1 gkg�1) was effective in preventing against pyloric-ligationinduced gastric ulceration and to mediate these effects byinhibiting gastric acid secretion, by increasing mucus wallthickness and reducing the levels of serum g-GTT.45

5.4.6 Ginger protects against ethanol-induced ulcer in rat.Ethanol is an important gastric ulcerogen and causes ulcers bygenerating free radicals.52 Animal studies with laboratory ratshave shown that oral administration of acetone extract of ginger(1000 mg kg�1), zingiberene (100 mg kg�1) and 6-gingerolsignicantly inhibited gastric lesions induced by HCl/ethanol.53

Animal studies have shown that oral pretreatment with gingerextract (500 mg kg�1) orally exert signicant cytoprotectionagainst 80% ethanol, 0.6 M HCl, 0.2 M NaOH and 25% NaClinduced gastric lesions.43 Aqueous extract of ginger rhizome(200 mg kg�1) is also reported to protect ethanol stress-inducedulcers in rats by recovering gastric mucus damage.54

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Additionally, recent studies also indicate that rats fed withspicy diet containing ginger (0.05% for 8 weeks) were protectedagainst ethanol-induced gastric and intestinal mucosal injuryby signicantly enhancing the activities of antioxidant enzymesSOD, CAT, GPrx and GST.55 The ginger phytochemicals like b-sesquiphellandrene, b-bisabolene, ar-curcumene and 6-shogaolhave also been shown to possess gastroprotective effect againstHCl/ethanol-induced gastric lesions.53

5.4.7 Ginger protects against swim stress-induced ulcer inrat. Stresses resulting from physiological and psychologicalfactors are shown to cause gastric ulcers by affecting gastroin-testinal defense and increasing accumulation of acid in thelumen. Pretreatment with aqueous extract of ginger (200 mgkg�1) protected rats against the gastric ulcers induced by swimstress by aiding recovery of gastric mucus damage andnormalizing the depleted antioxidant enzymes.54

5.4.8 Ginger protects against acetic acid-induced ulcer inrat. Acetic acid (50–60%) is an important experimental ulcer-ogen and has been regularly used to study the gastroprotectiveeffects of investigatory molecules. Administration of acetic acidincreases the XO activity, platelet aggregating factor formationand ROS all of which contribute to the pathological events.56,57

Ko and Leung,58 investigated the gastroprotective effects ofginger against the acaetic acid-induced ulcerogenesis andobserved that the cohorts pretreated with ginger extract hadreduced gastric ulcer area. Dose-dependent protective effectswere seen and biochemical studies showed to be mediated byattenuation of XO and MPO and reducing the levels of MDA inthe ulcerated mucosa.58

5.4.9 Effect of ginger against Helicobacter pylori infection.Helicobacter pylori amicroaerophilic bacterium is categorized asa group I carcinogen59 and a major contributor (70–80%) forpeptic ulcer and gastric cancer.59,60 Innumerable preclinicalstudies have shown the various extracts of ginger, the oil ofginger, gingerol containing fractions were effective in inhibitingthe growth of H. pylori,61–64 including against the highly virulentCagA+ strains.61 Seminal studies by Siddaraju and Dharmesh64

have also shown that the ginger-free phenolic and hydrolysedphenolic fractions inhibitedH. pylori growth and the effect to bebetter than that of lansoprazole.64 The ginger-free phenolic andginger-hydrolysed phenolic fractions are also reported topossess inhibitory effects on the growth of H. pylori, to scavengefree radicals, possess reducing power abilities, protects DNAand to inhibit lipid peroxidation.64 Laboratory studies have alsoshown that the pretreatment with the standardized gingerextract (100 mg kg�1) decreased H. pylori load, and reducedboth acute and chronic muscosal and submucosal inamma-tion, cryptitis, as well as epithelial cell degeneration and erosioninduced by H. pylori in mice.65

6 Effect of ginger on hyperglycaemia-induced gastric dysrhythmias

In people with diabetes, dyspepsia and other gastric ailmentsdue to gastropathy are common and these disturbances affecttheir quality of life. The pathogenesis of diabetic gastropathy ismultifactorial and is predominantly characterized by motor




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disturbances such as delayed gastric emptying, reduced antralcontractions, decreased fundic tone, pylorospasm, etc. Inpeople with diabetes, the degree of glycaemic control caninuence the magnitude of gastric motor and myoelectricdysfunction. During periods of hyperglycaemia gastricemptying is delayed and gastric slow wave dysrhythmiasbecome prominent.66 Double blind, placebo controlled studieswith healthy volunteers have shown, when compared to aplacebo, the cohorts receiving ginger had decreased theinduction of tachygastria in response to acute hyperglycaemia.66

Additionally, administering ginger did not affect the slow wavedisruptions elicited by 400 mg of misoprostol. These observa-tions clearly indicate that ginger mediates its antidysrhythmiceffects by preventing the production of prostaglandin duringperiods of hyperglycaemia.66

7 Mechanism/s of action7.1 Ginger scavenges free radicals

Free radicals like the ROS and RNS which contain one or moreunpaired electrons are extremely reactive and initiates/contributes to the pathogenesis and toxic effects of radiationand xenobiotic compounds.67–72 Experiments have shown thatginger extracts and its phytochemicals possess free radicalscavenging effects and to scavenge, superoxide, hydroxyl, nitricoxide and ABTS*+ radicals in cell free assays.67,68 The phyto-chemical zingerone was observed to scavenge superoxide,69

peroxyl,70 peroxynitrite71 and to inhibit the formation of perox-ynitrite-mediated tyrosine nitration.71 Another importantphytochemical of ginger,6-gingerol scavenged peroxyl radi-cals,70 and caused a dose-dependent inhibition of NO produc-tion and signicant reduction of iNOS in LPS-stimulatedJ774.1 cells.72

7.2 Ginger prevents oxidative damage to lipids

Free radicals induce damage to membrane lipids, proteins andDNA. Of the various lipid constituents the PUFA are highlyvulnerable to peroxidative attack and damage to these mole-cules alters the cell membrane structure, properties and func-tions.70 Ginger and its phytochemicals 6-gingerol and zingeronehave been shown to prevent/inhibit lipid peroxidationin vitro.70,73–75 Additionally, previous studies have also shownthat the polyphenols prevents lipid peroxidation of the food andto inhibit the absorption of the lipotoxin MDA into the bloodstream and, thereby also prevent atherogenesis.76 It is quitepossible that ginger mediates its protective effects on bothstomach and the vascular system through this mechanism andoffers additional benet to the individual.76

7.3 Ginger enhances antioxidant defense systems in vivo

Eukaryotic cells also contain certain molecules (glutathione,vitamin C, uric acid, albumin, bilirubin, vitamin E, carotenoidsand ubiquinone) and enzymes (SOD, GSH-Px and CAT) todetoxify the free radicals.77,78 Previous studies have shown thatginger reduces the oxidative stress by promoting antioxidantmechanisms.79–81 Ginger extract is shown to ameliorate ethanol-


induced gastric injury,55 indomethacin-induced gastric ulcera-tions43 and acetic acid-induced gastric inammation82 byenhancing the levels of antioxidant molecules and enzymes.

7.4 Ginger possesses anti-inammatory effects

Seminal studies carried out in the recent past indicate thatinammation plays a cardinal role in various pathophysiolog-ical processes and that it is mediated by TNF-a, NF-kb, i-NOSand COX-2, and increased generation of proinammatoryeisonaoids.83 Ginger and its compounds have been studied indetail for its anti-inammatory effects and studies have shownit to suppress synthesis of prostaglandin by inhibiting COX-1,COX-2 and the biosynthesis of leukotriene by inhibiting 5-LOX.84,85 The phytochemicals 8-paradol and 8-shogaol are alsoreported to possess strong inhibitory effects on COX-2 enzymeactivity in vitro.86 Ginger and its phytochemicals are also shownto decrease the levels of pro-inammatory cytokines (TNF-a, IL1b, IL-6 and interferon-g) and to reduce the elevated expressionof NFkB.87 Ginger extract inhibited the activity of COX-2, NF-kBand to inhibit the release of IL-1b, IL-6, IL-8, and TNF-a fromLPS-stimulated human peripheral blood mononuclear cells incombating H. pylori infection.65

7.5 Ginger modulates detoxifying enzymes

The enzymes belonging to the Phase I (Cyto P450, Cyto b5 etc.)and Phase II (GST, UDPGT etc.) categories are important in thedetoxication of xenobiotic compounds that have entered thesystem.88,89 Experimental studies have shown that feedingginger increases the levels of microsomal cytochrome P 450-dependent aryl hydroxylase, Cyto P450, Cyto b5, GST, UGT, arylhydrocarbon and quinone reductase in liver.88–92 Studies havealso shown that ginger oil also possesses benecial effects andto increase the activity of AHH and GST in mouse liver.92

7.6 Ginger modulates muscarinic and 5HT receptors andenhances gastric motility

Muscarinic receptor (M1 and M2) and 5HT are an integral partof the enteric nervous system and inuences GI motility. Ex vivostudies with the rat stomach fundus have shown that thehydromethanolic extract of dried ginger was effective inreversing the spasmogenic effects of Zo$Cr.93 Ginger and itsphytochemical gingerol mediated the anti-spasmogenic activityby inhibiting the butyrylcholinesterase and enhancing themuscaranic activity. Additionally experiments have also shownthat ginger possess calcium antagonistic activity leading tospasmolyis. The enhanced spasmolytic activity prevents thepossible gastric damage and ulcerogenesis by reducing thegastric emptying time and decreasing the contact time of acidicgastric contents with the mucosa.93 Ginger also stimulatessynthesis and secretion of mucin which acts as a buffer andthereby prevents the corrosive damage of HCl on the walls of thepyloric end of the stomach. Together all these observationsindicate that ginger, by stimulating the muscarinic receptorsand inhibiting 5-HT(3) receptors, mediates gastroprotectiveeffects.

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8 Conclusions

Preclinical studies have shown that ginger is effective as a gas-troprotective agent. However, the clinical data is insufficient todraw rm conclusions especially against motion and chemo-therapy-induced nausea and vomiting which may be due to thevariations in the bioactive compounds as these studies wereperformed in different countries. In view of these observationsit is imperative that some quality control is established for thepresence of active phytochemicals at the required levels. Addi-tionally, studies are also required to understand the optimalconcentration that is effective in mediating the optimal bene-cial effects as previous studies have shown that high concen-trations polyphenols act as prooxidants by generatingsuperuous levels of oxidants and that this may act negativelywhen overdosed.94–96 Due to its abundance, low cost and safetyin consumption, ginger remains a species with tremendouspotential and countless possibilities for further investigation.Ginger has the potential to develop as a non-toxic broad spec-trum gastroprotective agent when gaps existing in knowledgeare bridged. The outcomes of such studies may be useful for theapplications of ginger in various gastrointestinal ailments andmay open up newer therapeutic avenues.

Abbreviations

ABTS

852 | Food

2,20-Azinobis(3-ethylbenzothiazoline-6-sulphonicacid)

AHH
Aryl hydrocarbon hydroxylase CAT Catalase CINV Chemotherapy-induced nausea and vomiting COX Cyclooxygenase Cyto b5 Cytochrome b5 Cyto P450
Cytochrome P450

GLP
Glucagon like peptide GSH-Px Glutathione peroxidase GST Glutathione S-transferase H2R Histamine-2 receptors HT Serotonin IL Interleukin i-NOS Inducible isoform of nitric oxide synthase MDA Malondialdehyde MOP Myeloperoxidase NF-kb Nuclear factor kappa-light-chain-enhancer of
activated B cells
NK Neurokinin NSAIDs Non-steroidal anti-inammatory drugs PUFA Polyunsaturated fatty acids RNS Reactive nitrogen species ROS Reactive oxygen species SOD Superoxide dismutase TNF Tumor necrosis factor UDPGT Uridine 50-diphospho-glucuronosyltransferase UGT UDP-glucuronyl transferase XO Xanthine oxidase
Funct., 2013, 4, 845–855

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a review of the gastroprotective effects of ginger (zingiber officinale roscoe)

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