pancreatic200gana-894

Review1PlantsoftheGenusZingiberasSourceof2AntimicrobialAgents:fromTraditiontoPharmacy3MehdiSharifi-Rad1,ElenaMariaVaroni2,BahareSalehi3,*,JavadSharifi-Rad4,*,KarlR.
4Matthews5,SeyedAbdulmajidAyatollahi4,6,FarzadKobarfard4,7,SalamA.
Ibrahim8,Dima5Mnayer9,ZainulAmiruddinZakaria10,11,MajidSharifi-Rad12,ZubaidaYousaf13,MarcelloIriti14,*,6AdrianaBasile15,DanielaRigano16,*71DepartmentofMedicalParasitology,ZabolUniversityofMedicalSciences,Zabol61663-335,Iran;8mehdi_sharifirad@yahoo.
com92DipertimentodiScienzeBiomediche,ChirurgicheedOdontoiatriche,UniversitàdegliStudidiMilano,Italy;10elena.
varoni@unimi.
it113ZabolMedicinalPlantsResearchCenter,ZabolUniversityofMedicalSciences,Zabol,Iran;12bahar.
salehi007@gmail.
com134PhytochemistryResearchCenter,ShahidBeheshtiUniversityofMedicalSciences,Tehran,Iran;14javad.
sharifirad@gmail.
com155DepartmentofFoodScience,RutgersUniversity,NewBrunswick,NJ08901,NewJersey,USA;16bijan@sebs.
rutgers.
edu176DepartmentofPharmacognosy,SchoolofPharmacy,ShahidBeheshtiUniversityofMedicalSciencesTehran,18Iran;majid_ayatollahi@yahoo.
com197DepartmentofMedicinalChemistry,SchoolofPharmacy,ShahidBeheshtiUniversityofMedicalSciences,20Iran;farzadkf@yahoo.
com218FoodMicrobiologyandBiotechnologyLaboratory,171CarverHall,CollegeofAgricultureand22EnvironmentalSciencesNorthCarolinaA&TStateUniversityGreensboro,NC27411-1064;23ibrah001@ncat.
edu249FacultyofAgriculturalEngineeringandVeterinaryMedicine,LebaneseUniversity,Dekwaneh,Beirut6573,25Lebanon;d_mnayer@yahoo.
fr2610DepartmentofBiomedicalSciences,FacultyofMedicineandHealthSciences,UniversitiPutraMalaysia,27Selangor,43400Serdang,Malaysia;dr_zaz@yahoo.
com2811IntegrativePharmacogenomicsInstitute(iPROMISE),Level7,FF3Building,UniversitiTeknologiMARA,2942300PuncakAlam,Selangor,Malaysia;dr_zaz@yahoo.
com3012DepartmentofRangeandWatershedManagement,FacultyofNaturalResources,UniversityofZabol,31Zabol98615-538,Iran;majid.
sharifirad@gmail.
com3213DepartmentofBotany,LahoreCollegeforWomenUniversity,JailRoadLahore,Pakistan;33mussabuswaeshal@hotmail.
com3414DepartmentofAgriculturalandEnvironmentalSciences,MilanStateUniversity,Milan,Italy;35marcello.
iriti@unimi.
it3615DepartmentofBiologicalSciences—PlantBiologySection,UniversityofNaples"FedericoII",Naples80126,37Italy;adbasile@unina.
it3816DepartmentofPharmacy,UniversityFedericoIIofNaples,viaD.
Montesano49,CAP80131,Naples,Italy;39drigano@unina.
it4041*Correspondences:42bahar.
salehi007@gmail.
com(B.
S.
);javad.
sharifirad@gmail.
com(J.
S.
-R.
);marcello.
iriti@unimi.
it(M.
I.
);43drigano@unina.
it(D.
R.
);Tel.
:+98-22-51-790(B.
S.
);Tel.
:+98-88-200-104(J.
S.
-R.
);Tel.
:+39-02-5031-6766(M.
I.
);44Tel.
:+39081679897(D.
R.
)454647484950Preprints(www.
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org)|NOTPEER-REVIEWED|Posted:16November2017doi:10.
20944/preprints201711.
0102.
v12017bytheauthor(s).
DistributedunderaCreativeCommonsCCBYlicense.
Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
3390/molecules221221452of23Abstract:PlantsofthegenusZingiber(FamilyZingiberaceae)arewidelyusedthroughouttheworld51asfoodandmedicinalplants.
Theyrepresentverypopularherbalremediesinvarioustraditional52healingsystems;inparticular,rhizomeofZingiberspp.
plantshasalonghistoryofethnobotanical53usesbecauseofaplethoraofcurativeproperties.
Antimicrobialactivityofrhizomeessentialoilhas54beenextensivelyconfirmedinvitroandattributedtoitschemicalcomponents,mainlyconsistingin55monoterpeneandsesquiterpenehydrocarbonssuchasα-zingiberene,ar-curcumene,β-bisabolene56andβ-sesquiphellandrene.
Inaddition,gingerolshavebeenidentifiedasthemajoractive57componentsinthefreshrhizome,whereasshogaols,dehydratedgingerolderivatives,arethe58predominantpungentconstituentsindriedrhizome.
Zingiberspp.
maythusrepresentapromising59andinnovativesourceofnaturalalternativestochemicalfoodpreservatives.
Thisapproachwould60meettheincreasingconcernofconsumersawareofthepotentialhealthrisksassociatedwiththe61conventionalantimicrobialagentsinfood.
Thisnarrativereviewaimsprovidingaliterature62overviewonZingiberspp.
plants,theircultivation,traditionaluses,phytochemicalconstituentsand63biologicalactivities.
64Keywords:Zingiber;ginger;essentialoil;rhizome;herbalremedies;traditionalhealingsystems;65foodpreservatives66671.
Introduction68Today'sconsumersarebecomingmoreawareofthelinkbetweendietandhealth.
Forinstance,69Mediterraneandiet,possessesaplethoraofbioactivephytochemicals,e.
g.
polyphenolsand70melatonin[1,2],whichcancontributetoitsbeneficialeffectsagainstchronic-degenerativedisorders,71includingcancer,cardiovasculardiseasesanddiabetes[3-5].
Thistrendisleadingtoincreasing72demandfortheuseofnaturalingredientsasfoodsupplementsandpreservatives.
Inaddition,73increasingnumberofmicroorganismsthatarenotonlyantibioticresistant,butaremoretolerantto74existingpreservativetechniquesisofworldwideconcern[6].
Plantderivedextractsthathave75biologicalactivities,suchasantimicrobial,antidiabeticorantihypertensiveeffectshavethepotential76tofulfilltheneedforsafenaturalpreservatives[7-12].
Therefore,muchemphasishasbeenfocused77ontheinvestigationofplantderivednaturalsourcesofantimicrobials,compoundsthatcould78potentiallyreplacechemicalpreservativesandsyntheticantimicrobialingredients[13-17].
79Herbsandspices,whichareimportantpartofthehumandiet,havebeenusedforthousandsof80yearstoenhancetheflavor,colorandaromaoffood.
Inadditiontoboostingflavor,herbsandspices81arealsoknownfortheirpreservative,antioxidant,antimicrobialandothermedicinalproperties82[8,16,18].
ThegenusZingiber,belongingtothefamilyZingiberaceae,comprisesabout85speciesof83herbsmostlygrowninAsia,Central,SouthAmericaandAfrica[19].
Althoughdifferentmembersof84thisgenusaresomewhatsimilarinmorphology,theydifferwidelyintheirpharmacologicaland85therapeuticproperties[20].
86Themostpopularspice,ginger,comesfromtheundergroundstemsorrhizomesoftheplant87ZingiberofficinaleRoscoe.
Ithasbeenwidelyreportedinliteraturethatgingerisconsumedworldwide88asaspiceandflavoringagentandisattributedtohavemanymedicinalproperties[19,21-23].
89Theessentialoil(EO)fromZingiberrhizomeispaleyellowtolight-amber,containsboth90aromaticandpungentcompoundsandcanbeextractedwithyieldsrangingfrom1.
5-3.
0%,91dependingonthequalityofthecrop[24].
92PhytochemicalinvestigationoftherhizomesofseveralZingiberspp.
hasrevealedthepresence93ofbioactivecompoundssuchasgingerols,shogaols,diarylheptanoids,phenylbutenoids,flavanoids,94diterpenoidsandsesquiterpenoids[22].
Thegingerolsareidentifiedasthemajoractivecomponents95inthefreshrhizomeoftheplant.
Inaddition,shogaols,dehydratedgingerolderivatives,arethe96predominantpungentconstituentsindriedginger[25].
97Zingiberplantspossessvariouspharmacologicalandphysiologicaleffectsandarecommon98ingredientsintraditionalmedicines.
Therhizomeshavebeenshowntobeeffectiveinthetreatment99ofseveralmedicalconditionsincludingstomachproblems,nausea,vomiting,epilepsy,sorethroat,100Preprints(www.
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v1Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
3390/molecules221221453of23cough,commoncold,bruises,wounds,livercomplaints,rheumatism,muscularpains,101atherosclerosis,migraineheadaches,highcholesterol,ulcers,andstomachdiscomfort[26].
In102addition,phenoliccompounds,especiallythegingerols,ingingerroot,havebeenshowntohave103chemopreventiveeffectsthathavebeenassociatedwiththeirantioxidantandanti-inflammatory104activities[26].
105TheEOsofZingiberrhizomesareusedforpreservingvariousfoodsagainstautoxidationand106microbialspoilagebecauseoftheirantioxidantandantimicrobialproperties[24,27,28].
Manyinvitro107studiesdemonstratedtheantimicrobialpotentialofZingiberplantextractsagainstbothgrampositive108(Bacilluscereus,Staphylococcusaureus)andgramnegative(Escherichiacoli,Salmonellatyphi,109Pseudomonasaeruginosa,Klebsiellapneumonia)bacteria[29].
TheEOsalsoexhibitedsignificant110antifungalactivityagainstCandidaglabrata,C.
albicansandAspergillusniger[19].
Theseresultssuggest111thatEOofZingiberplantcouldbeusedinthetreatmentofmanybacterialandfungaldiseasesaswell112asinfoodpreservationasnaturalpreservative[20,24].
Themainaimofthispaperistoprovidean113overviewofthebiologicalactivityoftheZingiberspp.
EOsandtheircomponents,focusingonthe114potentialapplicationofZingiberplantsasnaturalpreservativesforfoods.
1151162.
GenusZingiberPlantCultivation117MostZingiberspp.
plantsarearomatic,perennialherbswiththecharacteristicofgrowing118horizontalorfibrousrhizomes.
Theyarecultivatedinmanycountries,thoughtheseplantsprefer119moist,tropicalconditions.
Gingerthrivesinwelldrainedsoilslikesandyloam,clayloam,redloam120orlateriticloam.
AfriableloamwithapHof6.
0to6.
5richinhumusisoptimalforproductionof121Zingiber.
Thecropprefersatemperaturerangeof19-28°Candahumidityof70-90%[30].
Before122cultivation,thelandneedstobeploughed4to5times.
Gingerispropagatedbyportionsofrhizomes123knownasseedrhizomes.
Preservedseedrhizomesarecarefullycutintosmallpiecesof2.
5-5.
0cm124lengthweighing20-25g;eachofthepieceshouldhaveoneortwobuds.
China,Indonesia,Nigeria,125Philippines,ThailandandIndiaarethemaingingerproducers.
Gingerreachesfullmaturityin210-126240daysafterplanting.
Harvestingofgingerforvegetablepurposestartsafter180daysbasedonthe127demand.
Asgingerisusedinmanydifferentformsandhighamountsareconsumedinthecountries128whereitisgrownorisusedtoprovideseedsforthenextcrop,itisdifficulttogetaccuratefiguresof129tradeofZingiber[31,32].
Toenhancetheproductivityofcrop,insomecountries,atthetimeof130planting,peopleusedecomposedcattlemanureorcompostat25-30tons/ha,eitherbybroadcasting131overthebedspriortoplantingorappliedinthepitsatthetimeofplanting.
Rhizomeseedgeneration132isdifficultandexpensive.
Therefore,peoplearelookingforothertechniquestocultivateZingibercost133effectively.
Atransplantingtechniqueingingerbyusingsinglebudsprouts(about5g)is134recommendedtoproducehighqualityplantingmaterialwithreducedcost.
Thetechniqueinvolves135raisingtransplantsfromsinglesproutseedrhizomesinthepro-trayandplantinginthefieldafter30-13640days.
Thistechniqueisgreatlyusefultoreducethequantityofrhizomeseed[30].
Toimprovethe137quality,insomecountries,croprotationandintercroppingtechniquesarealsoused.
Gingerisusually138intercroppedincoconut,arecanut,coffeeandorangeplantationsinKeralaandKarnataka[30].
139Changesinsoilfertilityforimprovedgrowthofgingerunderdifferentquantityofpigeonpea140hedgerowalleymanagementgavesignificantincreaseingingeryield[33].
Anotherimportant141techniqueispropagationbyusinginternodalcuttings[34].
Aeroponiccultivationofgingerhasalso142beenintroduced[35],aswellasmicropropagationandcytogeneticassessment[36].
1431443.
ChemicalCompositionofEssentialOilsObtainedfromGenusZingiberPlants145Preprints(www.
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v1Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
3390/molecules221221454of23ThegenusZingiberiswidelyusedintheworldforitsmedicinalandbiologicalproperties[37].
146Amongthisgenus,Z.
officinale(ginger)iswellknownandmostlystudiedforitshealthbenefits147[38,39].
148Aspreviouslyintroduced,thecolorofZ.
officinaleEOvariesfrompaleyellowtolightamberand149theextractionyieldrangesfrom1.
5to3%[40].
Differentstudieshavedocumentedtheirbiological150propertiessuchasantimicrobial,antioxidant,cytotoxic,insecticidal[41,42],anti-inflammatoryeffects151[39]aswellasfoodpreservativecharacteristics[43].
152ThesepropertieshavebeenattributedtothechemicalcomponentsofZ.
officinaleEO,mainly153consistinginmonoterpeneandsesquiterpenehydrocarbons(Fig.
1)[42].
Themostabundant154compoundsareα-zingiberene,responsibleforthedistinctiveflavorandaroma,geranial,ar-155curcumene,β-bisabolene,β-sesquiphellandreneandneral[27,44-46].
Otherpungentconstituents156foundinloweramountaregingerolandshogaol[47].
157However,theamountandthecompositionofthebioactivesubstancesmayvaryamong158differentZingiberspecies,andaccordingtodifferentfactorssuchastheextractionmethods,the159geographicandthegrowingconditions,theharvesttimeetc.
[46-49].
Table1showsthemajor160constituentsofEOsfromdifferentZingiberspecies,theextractionmethodsusedandtheirbiological161activities.
162Z.
officinaleEOwasobtainedusingdifferentextractionmethodsincludingconventional163hydrodistillation,microwave-assistedhydrodistillation,solventfreemicrowavehydrodistillation164andimprovedsolvent-freemicrowaveextractionwiththreetypesofmicrowave-absorptionmedium.
165Resultsshowedthatα-zingiberenewasthemostabundantcompoundfoundinallEOsstudied166rangingfrom17.
4to25.
4%,followedbyar-curcumene(14.
1-16.
4%),β-bisabolene(9.
9-12.
5%)andβ-167sesquiphellandrene(9.
7-13.
4%)[46].
Theseresultsareinaccordancewiththoseobtainedfromdried168gingerrhizomeEO,showingthatthemajorcomponentswereα-zingiberene(29.
5%)and169sesquiphellandrene(18.
4%)[50].
Again,α-zingiberenewasreportedasamajorconstituent(28.
62%)170foundinthefreshrhizomeEOofZ.
ofcinale,followedbycamphene(9.
32%),ar-curcumene(9.
09%)171andβ-phellandrene(7.
97%)[45].
172AcomparativechemicalcompositionwasconductedonfreshanddryrhizomeEOsbelonging173toZ.
officinalecv.
Nedumangadu.
α-Zingiberenewasthemajorcompoundfoundbothinfreshand174drygingerEOs(28.
6and30.
9%,respectively).
FreshgingerEOalsocontainedgeranial(8.
5%),ar-175curcumene(5.
6%)andβ-bisabolene(5.
8%),whereasar-curcumene(11%),β-bisabolene(7.
2%),β-176sesquiphellandrene(6.
6%)andgermacrene-D(4.
2%)werepresentinthedrygingerEO.
Freshginger177EOexhibitedhigherantibacterialactivityduetotheoxygenatedcompounds(29.
2%)whicharehigher178thanindrygingerEO(14.
4%)[51].
179ManyZ.
officinalecultivarswerestudiedandcomparedfortheirEOcomposition.
Seventeen180cultivarsfromnorthIndiawerestudiedfortheirchemicalcompositionandthemajorcomponents181werecamphene(8.
49±0.
41%),neral(4.
95±0.
34%),geranial(12.
36±0.
46%),α-zingiberene(20.
98±1822.
34%)andβ-sesquiphellandrene(7.
96±0.
66%)[52].
183ThreesubHimalayangingercultivars,namelyGorubathane,ShingboiandThingriawere184studiedfortheirEOcomposition.
Resultsshowedthatα-zingiberene(32.
2%)andβ-185sesquiphellandrene(10.
9%)werethemajorcompoundsinGorubathaneEO,whereasα-zingiberene186(12.
58%)andar-curcumene(9.
89%)weremostlypresentinThingriaEO.
However,geranial(20.
07%)187andneral(9.
44%)werethemainconstituentsfoundinShingboiEO[44].
188Preprints(www.
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v1Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
3390/molecules221221455of23ThecompositionofEOmayvarynotonlywithindifferentgingercultivars,butalsoaccording189tothepartsoftheplantstudied,asdemonstratedbySivasothyetal.
,[22]whoshowedthatthe190compositionofEOobtainedbyhydrodistillationoftheleavesandrhizomesofZ.
officinalevar.
191RubrumTheiladeweredifferent.
Infact,β-caryophyllene(31.
7%)wasthemajorcompoundfoundin192theleafoil,whilerhizomeoilwaspredominantlyrichinmonoterpenoids,suchascamphene(14.
5%),193geranial(14.
3%)andgeranylacetate(13.
7%).
194Regardingtheextractionmethodsused,waterandsteamdistillationwereusedtoobtainEO195fromVietnameseZ.
officinale.
ThemainEOcomponentsobtainedbywaterdistillationwereα-196cucurmene(11.
7%)andβ-bisabolene(4.
1%),whilethoseobtainedbysteamdistillationwerear-197curcumene(12.
6%),α-zingiberene(10.
3%),β-bisabolene(8.
1%)andβ-sesquiphellandrene(7.
4%).
The198differenceinthecompositioncanbebecause,duringwaterdistillation,therawmaterialwasin199contactwithwater,whichisnotthecaseduringsteamdistillation.
Asaresult,theextractionmethod200usedmayaffectthecompositionoftheEOreleased[48].
ThechemicalcompositionoftheZ.
officinale201EOspreviouslycitedisinaccordancewithanumberofstudieswhichreportedthepresenceofthese202majorcompounds,thoughfoundindifferentamounts[28,39,53].
203GingerEOrichinconstituentssuchasβ-sesquiphellandrene(27.
16%),caryophyllene(15.
29%),204α-zingiberene(13.
97%),α-farnesene(10.
52%)andar-curcumene(6.
62%)showedhighantimicrobial205andantioxidantactivities[28].
Z.
officinaleEOrichinar-curcumene(59%),β-myrcene(14%),1,8-cineol206(8%),citral(7.
5%)andα-zingiberene(7.
5%)exhibitedhighanti-inflammatoryeffects[54].
GingerEO207containinggeranial(25.
9%),α-zingiberene(9.
5%),(E,E)-α-farnesene(7.
6%),neral(7.
4%)andar-208curcumene(6.
6%)asmajorcomponentswasaneffectiveantibacterialandantifungalagent,aswell209asamorepowerfulantioxidantthanbutylatedhydroxyanisole(BHA)[27].
α-Zingiberene,akey210componentofgingerEO,wasfoundinlowamount(1.
64%)inthestudyconductedbyMesomoetal.
211[37].
Themaincomponentswerear-curcumene(11.
32%),geranial(10.
66%)followedbycamphene212(4.
88%),β-bisabolene(4.
45%)eucalyptol(3.
14%),isobornylformate(1.
95%).
213Apartfromthecommonginger(Z.
ofcinalis),manywildandcultivatedspeciesofthisgenus214havebeenstudiedacrosstheworldandcharacterizedforthebenecialphytochemicalspresentin215rhizomeEO[54].
216ThechemicalcompositionofaspeciesnativetoThailand,ZingibercassumunarRoxb.
,showed217thatmajorcompoundsweresabinene(36.
71-53.
50%),γ-terpinene(5.
27-7.
25%),terpinen-4-ol(21.
85-21829.
96%)and(E)-1-(3-,4-dimethoxyphenyl)butadiene(0.
95-16.
16%).
TheEOyieldrangedfrom1.
26%219to1.
37%[49].
TheseresultsareinagreementwithrecentresultsonZ.
cassumunarrhizomeEOwhere220themajorconstituentswereterpinen-4-ol(40.
5±6.
6%)andsabinene(17.
4±1.
4%)[55].
These221phytochemicalshaveshownvariouspharmacologicalproperties,includinganti-inflammatory,222antifungalandantibacterialeffects[56].
ThechemicalcompositionofZ.
cassumunarEOfromMalysia223showedthat6,9,9-tetramethyl-2,6,10-cycloundecatrien-1-one(60.
77%)andα-caryophyllene(23.
92%)224werethemostabundantcomponents[57].
225Theeffectsofthegrowingconditions,differentcultivationareasandharvesttimewerestudied226tocomparethecompositionofEOsfromZingibermontanumKoenig.
Resultsshoweddifferencesin227theirconstituentsaccordingtotheseexogenousfactors.
Themajorcomponentsmeasuredwere228sabinene(52.
64-56.
34%),terpinen-4-ol(7.
16-10.
17%)and(E)-1-(3-,4-dimethoxyphenyl)butadiene229(10.
88–14.
7%)[58].
230Preprints(www.
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v1Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
3390/molecules221221456of23Coralginger(ZingibercorallinumHance),anherbalremedyintraditionalChinesemedicine,was231studiedforitsrhizomeEO.
Sabinene(53.
38%),α-terpinene(3.
23%),γ-terpinene(2.
16%),terpinen-4-232ol(22.
66%),β-sesquiphellandrene(1.
41%)and1,4-bis(methoxy)-triquinacene(9.
64%)werethemajor233compounds[59].
234ThechemicalcompositionofZingiberzerumbet(L.
)Sm.
var.
DarcyiEOobtainedby235hydrodistillationfromtherhizomeshowedthatzerumbone(69.
9%),αhumulene(12.
9%),humulene236epoxideII(2.
5%),caryophylleneoxide(1.
1%)andcamphene(1.
9%)werethemajorconstituents[60].
237Zingibernimmonii(J.
Graham)DalzellisanendemicspeciesfromtheWesternGhats,inSouth238India.
ThemajorcomponentsoftherhizomeEOweredifferentfromtherhizomeEOobtainedfrom239otherspecies.
Themajorconstituentsweremyrcene(5.
1%),β-caryophyllene(26.
9%),α-humulene240(19.
6%)andα-cadinol(5.
2%)[61].
TheseresultsarealsoinaccordancewithSabulaletal.
[19]who241showedthatZ.
nimmoniiEOisauniquecaryophyllene-richnaturalsource.
242Zingibermoranisalocalgingervarietyendemictonorth-eastIndianregion,richincamphene,243citral,andlinalool[54].
Zingiberwrayivar.
HalabalaC.
K.
Lim,alocalherbfromtheBalaForestin244Narathiwat(Thailand),wasinvestigatedforitsEOcomposition.
Fourcompoundsincludingtrans-245anethole(96.
5%),estragol,camphorandm-phenylphenol[62].
246247248249250Figure1.
ChemicalstructuresofmajorcomponentsofZ.
officinale.
251252253Preprints(www.
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v1Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
3390/molecules221221457of23Table1:Extractionmethods,majorconstituentsandbiologicalactivitiesofZingiberspp.
essentialoils.
254PlantExtractionmethodsMajorcompoundsBiologicalactivitiesReferencesZofficinaleHydrodistillationar-curcumene(11.
32%),geranial(10.
66%),camphene(4.
88%),eucalyptol(3.
14%),isobornylformate(1.
95%),α-zingiberene(1.
64%)Antibacterial[37]Z.
officinaleHydrodistillation,microwaveassistedhydrodistillation,solvent-freemicrowavehydrodistillation,improvedsolvent-freemicrowaveextractionα-zingiberene(17.
4-25.
4%),ar-curcumene(14.
1-16.
4%),β-bisabolene(9.
9-12.
5%),β-sesquiphellandrene(9.
7-13.
4%)NR*[46]Z.
officinaleHydrodistillationGeranial(25.
9%),α-zingiberene(9.
5%),(E,E)-α-farnesene(7.
6%),neral(7.
4%),ar-curcumene(6.
6%)Antibacterial,antifungal,antioxidant[28]Threesub-HimalayanZ.
officinaliscultivars(Gorubathane,ShingboiThingriaHydrodistillationGorubathane:α-zingiberene(32.
2%),β-sesquiphellandrene(10.
9%);Thingria:α-zingibirene(12.
58%),ar-curcumene(9.
89%);Shingboi:geranial(20.
07%),neral(9.
44%)NR[44]FreshanddryZ.
officinalevar.
NedumangaduHydrodistillationFreshginger:α-zingiberene(28.
6%),geranial(8.
5%)ar-curcumene(5.
6%),β-bisabolene(5.
8%);Dryginger:α-zingiberene(30.
9%),ar-urcumene(11%),β-bisabolene(7.
2%),β-sesquiphellandrene(6.
6%),germacrene-D(4.
2%)Antibacterial,antifungal[51]Z.
officinaleHydrodistillationα-zingiberene(28.
62%),camphene(9.
32%),ar-curcumene(9.
09%),β-phellandrene(7.
97%)Antifungal,antioxidant[45]Preprints(www.
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v1Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
3390/molecules221221458of23Z.
officinaleHydrodistillationβ-sesquiphellandrene(27.
16%),caryophyllene(15.
29%),zingiberene(13.
97%),α-farnesene(10.
52%),ar-curcumin(6.
62%)Antibacterial,antioxidant[28]Z.
montanumHydrodistillationSabinene(52.
64-56.
34%),terpinen-4-ol(7.
16-10.
17%),(E)-1-(3-4-dimethoxyphenyl)butadiene(10.
88-14.
7%)NR[58]Z.
cassumunar(threenativecultivars)HydrodistillationSabinene(36.
71-53.
50%),γ-terpinene(5.
27-7.
25%),terpinen-4-ol(21.
85-29.
96%),(E)-1-(3-4-dimethoxyphenyl)butadiene(0.
95-16.
16%)NR[49]Z.
cassumunarSteamdistillation6,9,9-tetramethyl-2,6,10-cycloundecatrien-1-one(60.
77%),α-caryophyllene(23.
92%)Slightantimicrobial[57]Z.
officinaleSteamdistillationar-curcumene(59%),b-myrcene(14%),1,8-cineol(8%),citral(7.
5%),andα-zingiberene(7.
5%)Inflammatoryeffects[39]Z.
zerumbetvar.
DarcyiHydrodistillationzerumbone(69.
9%),α-humulene(12.
9%),humuleneepoxideII(2.
5%),caryophylleneoxide(1.
1%),camphene(1.
9%)NR[60]Z.
corallinumSteamdistillationSabinene(53.
38%),ɑ-terpinene(3.
23%),γ-terpinene(2.
16%),terpinen-4-ol(22.
66%),β-sesquiphellandrene(1.
41%),1,4-bis(methoxy)triquinacene(9.
64%)NR[59]Z.
nimmoniiHydrodistillationMyrcene(5.
1%),β-caryophyllene(26.
9%),α-humulene(19.
6%),α-cadinol(5.
2%)Larvicidalandrepellent[31]Z.
nimmoniiHydrodistillationβ-caryophyllene(42.
2%),α-humulene,α-caryophyllene(27.
7%)Antimicrobial[19]Z.
moranHydrodistillationCamphene,citral,linaloolCytotoxic[54]Z.
wrayivar.
Halabala,SteamdistillationTrans-anethole(96.
5%)Antibacterial[62]*NR,notreported255256Preprints(www.
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org)|NOTPEER-REVIEWED|Posted:16November2017doi:10.
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3390/molecules221221459of232574.
ThegenusZingiberinTraditionalHealingSystems2582594.
1.
MedicinalUsesofGinger260Ginger(Z.
officinale)isanimportantplantwithseveralmedicinal,ethnomedicinaland261nutritionalvalues.
Amongdifferentbiologicalactivities,gingerhasdemonstratedanti-inflammatory,262antioxidant,anti-emetic,analgesic,andantimicrobialactivities.
Overall,theycanbemainlyascribed263to6-gingeroland6-shogaol,whichrepresentthemajorcompoundsingingerrhizomes,among264hundredsofmoleculesisolated[63,64].
265Accordingtorecentliterature,gingeranti-inflammatorypropertiesaremediatedbythe266inhibitionof5-lipoxygenaseorprostaglandinsynthetase,whichreducesbiosynthesisof267prostaglandins,leukotrienesandpro-inflammatorycytokinessuchasIL-1,IL-8;TNF-α,andNFκB268[63].
Oneclinicaltrial,indeed,reporteditsbeneficialeffectsinreducingpro-inflammatorycytokines269ofpatientssufferingfromosteoarthritis[65].
Inaddition,theantioxidantactivityoftheZ.
officinale270extract[66]hasbeeninvitrodemonstratedtoinhibitthehydroxylradicalsandthelipidperoxidation271products.
Thiswasconsistentwithfurtherstudiesinanimalmodels,whichrevealedasitactedby272enhancingantioxidantenzymedefensesandserumglutathione[67].
Similareffectswereattributed273togingersingleconstituents,namely6-gingerol,8-gingerol,10-gingerol,and6-shogaol[68]aswell274asgeranialandneral,α-zingiberene,camphene,α-farnesene,β-sesquiphellandrene[69]and275zingerone[67].
6-Shogaol,inparticular,showedthemostpotentantioxidantandanti-inflammatory276properties,duetothepresenceofα,β-unsaturatedketonemoiety[67],whilezingeroneexhibited,in277mice,protectionagainstradiation-inducedtoxicity,increasingantiapoptoticmolecules(Bcl-2)while278reducingtheproapoptoticones(Bax)[70].
279Together,theabovereportedantioxidantandanti-inflammatorypropertiesofgingersupport280itspreventiveroleagainstaplethoraofchronic-degenerativediseases[71],includingcancer,281cardiovasculardisorders,anddiabetes.
282Althoughstillunderdebate,anticanceractivityofgingeris,asmentionedabove,mainlyrelated283tothehighcontentof6-gingeroland6-shogaol.
Gingerandrelatedbioactivemolecules,indeed,are284effectiveincontrolling,invitro,viabilityandinvasivenessofcolorectal,gastric,ovarian,liver,skin,285breast,andprostatecancercells[67].
Recentevidencesupports,inparticular,theroleofzingerone286supplementationaschemopreventiveagent,reducingcancerincidenceindimethylhydrazinetreated287rats;themechanismincludedtheinhibitionofcellproliferation,theinductionofcellapoptosis,and288thesuppressionofNF-κBandhemeoxygenase(HO)-1expression[70].
Theproapoptoticeffectand289thepromotionofcellcyclearrestinhepatomaandprostatecancercellswereascribedtotheactivation290ofcaspasecascadeandtheimpairmentofthenucleartranslocationofNF-κB,particularlyby6-291gingerol[70],whichwasalsoabletoinhibitangiogenesisandinvasivenessinthemurinecancer292models[70].
Anti-angiogeneticactivityof6-gingeroloccursbytheinhibitionofthevascular293endothelialgrowthfactor(VEGF),whileitsanti-metastaticactivitycouldbeascribedtoregulationof294matrixmetalloproteinases2/9transcription[64].
Anotheractivecompoundcontainedingingeris295zerumbone,whichinducedapoptosisinpancreaticcarcinomacells,throughp53signalpathwayand296increasingtheactivityofcaspase-3[70].
Inhumans,thechemopreventiveeffectofgingerhasbeen297mainlyinvestigatedagainstcolorectalcancer,invirtueofitsanti-inflammatoryeffects,similarlyto298Preprints(www.
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GingersignificantlyloweredCOX-1proteinexpressioninpatientsatincreasedrisk299forcolorectalcancer[72],butwithnoeffectoneicosanoidlevels[73].
300Theroleofgingerinreducingcardiovasculardiseasesanddiabetesishighlyrelatedtoitsability301incontrollingbodyweight,andreducingserumlevelsofglucoseandlipids.
Indeed,astudyshowed302thatgingersignificantlydecreasedglucose,totalcholesterol,triglycerides,freefattyacids,LDLand303VLDL,whilstraisedHDLinserumofratswithdiabeticorfedwithahighfatdiet[67].
Theseeffects304aremainlyrelatedtozingerone[70],andlesstoshogaols[64].
Recently,inhighfatdietfedanimals,305zingeroneand6-gingerolbothpossessedhighlipolyticactivity:theformerbyincreasingtheactivity306ofnorepinephrine-sensitivelipases,enhancingbasallipolysisandisoprenaline-inducedlipolysisin307adipocytes[64],whilethelatterbyreducingthelevelsoffattyacidsynthaseandadipocyte-specific308fattyacidbindingprotein[64].
Inaddition,6-gingerolcouldpreventdiabetesviatheimprovement309ofadipocytedysfunction,sinceitcausedtheinhibitionoftheTNF-αmediateddown-regulationof310adiponectinexpression,aswellasarachidonicacidpathwayinturninhibitinganti-platelet311aggregation[64].
Aclinicaltrialshowedthatgingerconsumptionenhancedthermogenesisand312reducedfeelingofhunger,suggestingapotentialroleinweightcontrol[74].
Inpatientswithtype2313diabetes,gingerimprovedglycemicindex,totalantioxidantcapacity[75],insulinsensitivityandlipid314profile,reducingc-reactiveproteinandprostaglandinE[76,77].
Inperitonealdialysispatients,for315whomoneofthemajorriskfactorsforcardiovasculardiseaseisserumtriglycerideconcentration,the316latterresultedreducedbydailyadministrationof1,000mgginger[78].
317Asantimicrobialagent,gingerextractexhibitedhigherantifungalthanantibacterialeectsin318vitro,showinganti-Candidaactivityagainststrainsisolatedfrompatients.
Thisfindingwasrelatedto319thehighanti-biofilmactivityagainstC.
albicans,atconcentrationsrangingfrom0.
625mg/mLto5320mg/mL[79].
Gingerwasalsoeffectiveagainstotherfungalstrains,suchasFusariumspp,andit321inhibitedthegrowthoffungithatwereresistanttoamphotericinBandketoconazole[80-82].
Among322bacteria,itshowedefficacyagainstPseudomonaaeruginosa,Staphylococcusaureus,Acinetobacter323Baumannii[79],EscherichiaColi,BacillussubtilisandSalmonellaTyphi[83].
Furthermore,6-gingeroland32412-gingerolshowedantibacterialactivityagainstperiodontalbacteria[83],sothataclinicaltrialwas325performedtotestapolyherbalmouthwashcontaining,amongtheothers,thehydroalcoholicextract326ofZ.
officinale;noteworthy,itwaseffectiveinreducinggingivalandplaqueindicessimilarlyto327chlorhexidinemouthwash[84].
Ontheotherhand,theantidiarrhealactivityof6-gingerolhasbeen328accreditedtoitsabilitytobindtothetoxinproducedbyVibriocholera,ratherthanduetodirect329antibacterialactivity[64].
330Nauseaandemesisareamongthemostcommonadverseeffectsofchemotherapeuticsaswell331asfrequenteventsduringpregnancyandpost-surgeryanesthesia.
Atpreclinicallevel,6-gingerol332showedefficacyinratsagainstcisplatin-inducednauseaandvomiting[64].
Alongtheselines,a333numberofclinicaltrialsandrelatedsystematicreviewsandmeta-analysisnowsupporttheefficacy334ofgingerinreducinghyperemesisduringpregnancy[85,86]aswellasinalleviatingnauseaand335vomitingduringchemotherapy,especiallyforbreastcancer[87].
Similarly,gingerappearedtoreduce336post-anesthesiaemesisingynecologicalsurgery[88]andafterantitubercolosisdrugadministration337[89].
338Analgesicandantipyreticactivitiesofgingercanbeascribedto6-gingerol,asshowninrats[64].
339Injectionof10gof6-gingerolintotheratspinalcordwasfoundtobeeffectiveinameliorating340neuropathicpain,viavanilloidreceptor-mediatedpathway[64].
Inhumans,gingerintakeproduced341Preprints(www.
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3390/molecules2212214511of23painreliefinprimarydysmenorrheasimilarlytoconventionalanalgesicdrugs[90,91],while342remainingcontroversialincaseofostheoartritis[92,93].
Inaddition,itshowedabortiveeffectagainst343migraine[94]particularlywhenadministeredearlyandinpresenceofmildmigraine[95].
344Furtheractivitiesincludegastroprotective,immunomodulatory,anti-allergyand345hepatoprotectiveproperties,inallcasesmainlyrelatedto6-gingerol[64].
Inparticular,ginger346reducedthegastropathyinducedbysomedrugs,suchasanti-tuberculosisagents[96]andnonsteroid347anti-inflammatorydrugs[97]348Duetotheseoverwhelmingactivitiessupportedbypreclinicalevidences,peopleofdifferent349cultureshavetraditionallyappliedgingerasmedicinalagentsincealongtimeago.
Avastbodyof350anecdotalevidence,whichcanbeusedtosupportgingerusesandefficacy,canbefoundinvarious351traditionalsystemsofmedicinebelongingtoIndian,Unani,Chinese,Japaneseandothercultures352[98].
3533544.
1.
2.
GingerintheIndianSystemofMedicine355GingerplaysanimportantroleintraditionalIndianmedicine.
Itisalsousedasaningredientin356traditionalIndiandrinks.
Freshgingerisoneofthemainspicesusedformakingdishes,both357vegetarianandnon-vegetarianfoods.
IntheAyurvedasystemofmedicine,ginger,eitherfreshor358dry,hasbeenwidelyusedasacommonhouseholdremedyforvariousillnesses[99,100].
Commonly,359bothtypesofginger,whichhavesimilarproperties,actasanappetizer,carminative,andstomachic360[101].
Otherthanthat,gingerisacrid,analgesic,antirheumatic,antiphlegmatic,diureticand361aphrodisiac.
Gingerisalsousedtotreatasthma,bronchitis,piles,eructation,andascites,tohelp362cleansesthethroat,isusefulforthevoice(correctiveoflarynxaffections),subsidesvomiting,relieves363flatulenceandconstipation,actsasaremedyforcoughandrelievesneckpain.
Inaddition,the364Ayurvedasystemalsocitedthatgingerhasanti-inflammatoryandanti-edematousactivities.
Dueto365itshotproperty,gingercancausedrynessand,thus,isantidiarrheal[30].
Moreover,gingerisapplied366externallytoboilsandenlargedglands,andinternallyasatonicinCambodia[102].
Accordingto367Nadkarni[103],gingeralsostrengthensmemoryandremovesobstructioninthevessels,incontinence368ofurine,andnervousdiseases.
369Specifically,thefreshgingerisusedtogetherwithhoneyandgheeasaremedyforcoughor370aloneasaremedyforacuteasciteswithdropsyarisingfromlivercirrhosis.
Additionally,thejuiceis371appliedasastrongdiuretic[102].
Theouterskinofgingerisusedasacarminativeandissaidtobe372aremedyforopacityofcornea.
Ontheotherhand,thedrygingerhasbeenreportedtopossess373antiarthriticandantifilarialactivities[102]whilethepasteofdrygingerwithwateriseffectivein374recoveringfromfaintingandisalsoappliedexternallytotheeyelids.
Inaddition,thegingerpowder375canalsobeusedasasnuff.
Thedryginger,incombinationwithdryrocksalt,longpepperandblack376pepperispowderedandthenmixedwithfreshgingerjuiceandusedasagargle,andforthe377treatmentofphlegmaticaffectionsoftheheart,head,neck,andchest.
Moreover,thecombinationcan378alsoexertremarkableeffectsagainstalltypesofseverefeversandtheirassociatedsymptoms.
379Otherthanitsusestotreathumanaffections,gingerisusedofinveterinaryasastimulantand380carminative,inindigestioninhorsesandcattle,inspasmodiccolicofhorses,andtopreventgripping381bypurgatives[104].
382383Preprints(www.
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org)|NOTPEER-REVIEWED|Posted:16November2017doi:10.
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1.
3.
GingerintheChineseandJapaneseSystemsofMedicine384GingerrhizomeisanimportantdrugintheChineseandJapanesemedicinalsystems[98].
In385Chinesemedicine,thefreshginger(RhizomaZingiberisRecens)isusedasanantiemetic,antitussive,386orexpectorant,andisusedtoinduceperspirationanddispelcold,whereasthedriedgingerisused387forstomachache,vomiting,anddiarrheaaccompaniedbycoldextremitiesandfaintpulse[105].
In388ChineseMateriaMedica,BenskeyandGamble[105]citedthatgingerhastheabilityto:i)releasethe389exterioranddispersescold-usedforexteriorcoldpatterns;ii)warmthemiddleburnerandalleviates390vomiting-usedforcoldinthestomach,especiallywhenthereisvomiting;iii)dispersecoldand391alleviatescoughing,usedforcoughingfromacutewind,coldcoughpatterns,andchroniclung392disorderswithphlegm;iv)reducethepoisonouseffectsofotherherbs-usedtodetoxifyortreat393overdosesofotherherbssuchasRadixAconitiCarmichaeliPraeparata(Fuzi)orRhizomaPinelliae394Ternata(BanXia).
3953964.
1.
4.
GingerintheUnaniSystemofMedicine397IntheUnanisystem,gingerisusedforitsanthelmintic,aphrodisiac,carminative,digestive,and398sedativeproperties;inheadache,lumbago,nervousdiseases,pains,andrheumatism;andfor399strengtheningofmemory[103].
Gingerisalsousedinveterinarymedicineinhorsesandcattlefor400rheumaticcomplaints,asanantispasmodicandacarminativeinatonicindigestion[106,107].
4014024.
2.
ExamplesofGingerSpeciesandtheirUsesinTraditionalMedicine403Gingerhasbeenusedastraditionalmedicinesinceancienttimes.
Itisconsideredasamedicinal404plantaswithseveralcurativepropertiesintreatingdifferentdiseases.
Inthefollowingsectionsare405reportedsomegingerspeciesknownfortheirmedicinalproperties.
4064074.
2.
1.
ZingiberofficinaleRoscoe408Z.
officinaleisthebestknownZingiberplantinthegingerfamilyandisalsoreferredtoasgarden409gingerorcommonginger.
ThisgingerisusedinAyurvedaandChinesemedicine,aspreviously410mentioned,inbothfreshanddriedpreparations,forcuringheartproblems,treatstomachupset,411diarrhea,headaches,andnausea.
Otherthanthat,Z.
officinalehasalsobeenusedtopromotethe412releaseofbilefromthegallbladder,reducejointpainfromarthritis,treatheartandlungdiseases;413reliefcoughandcold,throatinfectionandeventheremovalofwartsandcorns.
InboththeChinese414andJapanesesystemsofmedicine,freshgingerisusedforitswarmingpropertiesandasaremedy415forcoughsandnausea,whereasdriedgingerisindicatedforailmentsofthedigestivesystem.
In416aromatherapy,theessentialoilofgingerisusedformuscleandjointpain,sprains,colds,nausea,417diarrhoea,alcoholismandhelpingthehealingofbrokenbones[108-110].
TherhizomeofZ.
officinale418canalsobepreparedasateaforindigestionandincreasingthebloodcirculationandsenseofwell-419being[111].
Inaddition,therhizomeextractshavebeenusedinMalaytraditionalculturetotreat420varioustypesofailmentssuchasinflammatory-andpain-mediateddiseases,worminfestation,and421diarrhea.
4224234.
2.
2.
Zingibermontanum(J.
Koenig)LinkexA.
Dietr.
424TherhizomesofZ.
montanum,alsoknownas"cassumunarginger",areusedthroughouttropical425Asiaprimarilyasacarminativeandstimulantforthestomach,andagainstdiarrheaandcolic426Preprints(www.
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org)|NOTPEER-REVIEWED|Posted:16November2017doi:10.
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v1Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
3390/molecules2212214513of23[112,113].
ThepoundedrhizomeistraditionallyusedinIndonesiaasapoulticeagainstheadache427whiletheMalaysiansusedtherhizomeinternallyasavermifugeandforpostpartummedication.
428Moreover,inLaostherhizomeisappliedagainstabscesses,fever,colic,diarrheaandotherintestinal429disorders,asadepurative,aswellasapoisonantidote,whereas,inThailand,therhizomesaretaken430againstasthmaandusedasthemainingredientinmassageoiltorelievemusclepain[112,114].
Other431thanthat,therhizomepasteisconsumedorallybythepeopleleavinginNortheastIndiatotreat432dyspepsiaandstomachbloating[113,114].
4334344.
2.
3.
Zingibermioga(Thunb.
)Roscoe435AlsoknownasJapanesegingerormyogaginger,thisperennialherbisnativetoJapan,China436andthesouthernpartofKorea.
Thesubterraneanstemandyoungflowerbudsofthisspeciescanbe437usedtocuremenstrualirregularity,leucorrhea,heartdisease,andeyeinflammation.
Itcanalsobe438usedasanexpectorant.
Inaddition,Z.
miogaisusedtotreatcoughandrheumatisminChinaand439consumedthroughoutJapantorelieveinsectbites,eyeinflammation,coughandrheumatism440[115,116].
4414424.
2.
4.
ZingiberspectabileGriff.
443NativetomaritimeSoutheastAsiasuchaspeninsularMalaysiaandpeninsularThailand,itisa444speciesofgingercommonlyknowninthewestas"beehiveginger".
DifferentpartsofZ.
spectabileare445widelyusedintheMalaytraditionalmedicinetotreatvariousailments.
Forexamples,thepounded446leavesareusedaspoulticetotreatswellingorappliedtopicallytotherequiredpartofthebodyto447treatburns,backaches,headachesandbackpain[116].
Thejuicefromleaveshasbeenusedbythe448Temuantribe,whichisoneoftheindigenouspopulationsfoundinAyerHitamForest,Perak,449Malaysia,totreateyeinfectionsandtosootheswolleneyes[117].
InThailand,thefreshpoundedleaf450infusioncanbeusedtowashtheinfectedeyelidsortreatinflammationoftheeye[118].
Moreover,451thepasteofZ.
spectabilefreshleavesispatchedontoopenwoundstohealthem,whilethewater452obtainedfromboilingtheleavesissaidtobeeffectiveagainstsinusailments,andisusedasafacial453andnasalwash.
Therhizomesareusedinthetreatmentsofcancer,coughandasthma,asastimulant,454tonicandgermicide.
Z.
spectabileisalsousedinrecipesformedicinalbathbymothersaftergiving455birthandduringthematernityperiod,especiallyforpost-natalbathbyboilingthewholeplant[119].
4564574.
2.
5.
Zingiberzerumbet(L.
)Sm.
458Z.
zerumbet,alsoknownasshampoogingerandnativetoIndia,isfoundinmanytropical459countries.
Therhizomeextractsofthisspecieshavebeenusedtotreatadiverserangeofailments.
460Forexamples,theHawaiiansappliedthefreshpoundedrhizomeasmedicineforindigestionand461otherailments.
Traditionally,thegroundrhizomes,mixedwitharipenoni(MorindacitrifoliaL.
)fruit,462canbeusedtotreatseveresprainswhilethepulp,placedinacloth,canbelooselyboundaroundthe463injuredarea.
Thecookedandsoftenedrhizomecanalsobeusedtotreattoothacheorcariesby464pressingitintothehollowandleftforaslongaswasneeded,whilethegroundandstrainedrhizome465materialismixedwithwateranddrunktotreatastomachache[120].
466Otherthanthat,therhizomeofZ.
zerumbethasbeengenerallycitedtobeusedinthetreatment467ofinflammation,diarrhea,stomachcramps,bacterialinfections,fever,flatulence,allergiesand468poisoning.
Thepowderedrhizomesareusedinthetreatmentofearinfectionsandtoothache,while469Preprints(www.
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org)|NOTPEER-REVIEWED|Posted:16November2017doi:10.
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0102.
v1Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
3390/molecules2212214514of23theteaofZ.
zerumbetrhizomeisusedtotreatstomachdisease.
Inaddition,thejuiceofcooked470rhizomecanbeusedinthetreatmentofworminfectioninchildren.
Theleavesarealsousedin471therapiesforjointpain[121].
4724734.
2.
6.
ZingiberottensiiValeton474InIndonesia,thestemistraditionallyusedaspartofasedativelotionbytheJavanesepeople,475while,inSumatra,thestemisusedaspotherbforpostpartumcare.
Ontheotherhand,thetraditional476midwivesinPerak,Malaysia,usedtherhizomesandleavesasapoulticeappliedonthebodyofthe477womeninconfinement.
Inaddition,theleavesareusedasapoulticeforlumbago[122].
Thepungent478rhizomesarepoundedintoapoulticeandusedbywomenafterchildbirth,orareaddedtoamixture479tomakeasedativelotionoratonic[123].
4804814825.
EssentialOilObtainedfromGenusZingiberPlantsasaFoodPreservative483484Consumersareincreasinglyconcernedwiththeuseofchemicalagentsinfoods.
Thedesireto485seeknovelfoodantimicrobialsisnotoutoffearthatmicrobesinfoodhavedevelopedresistanceto486traditionalfoodantimicrobials.
Traditionalfoodantimicrobialsareprovenandremainextremely487effectiveinachievingshelflifeandfoodsafetygoals.
Whentraditionalantimicrobialsareevaluated488underrealfoodprocessing/handlingconditions,antimicrobialresistancedoesnotappeartobea489majorphenomenon[124].
Theconcernofmanyconsumerscentersonthepotentialhealthrisksthat490maybeassociatedwiththeantimicrobialitselfanditsby-products.
Theconsumertodayvalues491productsthathave"natural"preservativesanda"cleanlabel"orproductswithnoartificial492ingredientsandchemicals.
493Awealthofnewtechnologiesincludinghighhydrostaticpressure,ionizationradiation,and494bioactivepackagingcanreduceoreliminatetheneedforutilizationoftraditionalfoodpreservatives.
495Themajordrawbackofthesetechnologiesisassociatedwithcostandfeasibilityofuseinarangeof496foodproducts.
Inthepastdecade,increasedattentionhasbeenfocusedontheutilizationofplant497essentialoilsasnaturalantimicrobialsinfoods.
Essentialoilshavebeenfoundtoexhibitabroad498rangeofactivityagainstspoilageandpathogenicbacteriaassociatedwithfood.
Essentialoilsderived499fromThymusvulgaris(thyme),Origanummajorana(marjoram),Origanumvulgare(oregano),Ocimum500basilicum(basil),Cymbopogoncitratus(lemongrass),andCaryophyllusaromaticus(clove)havebeen501evaluatedfortheabilitytocontrolorinactivatevariousfoodbornepathogensinvitroorinselectfoods502[125].
Akeyadvantagetotheuseofessentialoilsfromthoseplantsistheyareconsideredgenerally503recognizedassafe(GRAS)foruseinfood.
504Aspreviouslyintroduced,gingerisanimportantspiceusedthroughoutAsiaandhasgained505considerableglobalpopularityasaningredientinfoodduetoitsuniqueflavor.
Theflavorisderived506frombothvolatileandnon-volatilecompounds;theseincludegingerol,shogaol,andzingiberene.
507Compoundsimportanttoantimicrobialactivityincludecamphene,linalool,α-pinene,andborneol.
508AntimicrobialactivityofgingeressentialoilshasbeenevaluatedagainstAeromonashydrophila,509Bacillussubtilis,Bacilluscereus,Listeriamonocytogenes,Salinococcusroseus,Halococcusturkmenicus,510Halococcusmorrhuae,Pseudomonasaeruginosa,Staphylococcusaureus,Salmonellaspp.
,Escherichiacoli,511Preprints(www.
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org)|NOTPEER-REVIEWED|Posted:16November2017doi:10.
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v1Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
3390/molecules2212214515of23Vibriocholera,Vibrioparaheamolyticus,Aspergillusniger,Mucorspp.
,Candidaalbicans,andPenicillium512spp.
[8,125-128].
513Thepartoftheplant(leaforrhizome)utilizedandmethodofextractionofessentialoilscanhave514aprofoundimpactonantimicrobialactivity[37,129].
Muchoftheresearchonantimicrobialactivity515ofessentialoilsofgingerhasbeenconductedinvitrowhichissimilarforessentialoilsfromother516plants.
Althoughthisisagoodstartingpoint,thelevelofantimicrobialactivityobservedmaynotbe517comparableinacomplexfoodmatrix.
Gingeressentialoilsextractedfromleafandrhizomeexhibited518antibacterialactivityagainstB.
licheniformis,B.
spizizenii,S.
aureus,E.
coli,K.
pneumoniae,andP.
stutzeri519(MIC=0.
16-0.
63mg/mL)[22].
Ingeneral,activitywashigheragainsttheGram-positivebacteria520evaluated.
Thesefindingsareinagreementwithothersstudieswheregingeressentialoilswere521evaluatedagainstGram-positiveandGram-negativebacteriausingdisc-diffusionorbrothassays522[24,130,131].
523Theantimicrobialactivityofgingeressentialoiliscomparableorhigherthanessentialoilsfrom524otherplants.
Acomparisonofginger,eucalyptus,andsweetorangeessentialoilsfoundthatginger525essentialoilexhibitedthehighestantibacterialactivity[85].
However,V.
parahaemolyticuswas526resistanttoalltheessentialoilsevaluated.
Ginger,thyme,coriander,marjoram,mustard,chamomile,527licoriceandnigellaessentialoilswereevaluatedfortheiractivityagainstGram-negativeandGram-528positivefoodbornepathogens[132].
Ginger,thyme,andcoriandershowedthehighestantibacterial529inhibitionagainstthestrainsofbacteriatested.
530Yeastsandmoldscanpresentrelevantproblemsinfood.
Yeastsareassociatedwithfood531spoilageandpresentnohumanhealthconcern,whereasmoldsareassociatedwithspoilageandcan532producemycotoxinswhich,intheworstcasescenario,canresultinchronictoxicityanddeath.
533EssentialoilsofgingerexhibitedpooractivityagainstPenicilliumspp.
(MIC=869.
2mg/mL)andno534activityagainstA.
niger[24].
Theseresultsareinagreementwithotherreports[86].
Incontrast,ginger535essentialoilwasreportedtoinhibitthegrowthofFusariumverticilliodes(MIC=2500g/mL)andthe536productionoffumonisinB1andfumonisinB2atconcentrationsof4000and2000g/mL,respectively537[88].
Thegrowthofyeasts,CandidatropicalisandCandidautilis,wasnotinhibitedbyexposureto538gingeressentialoil[131].
539Theantimicrobialeffectofgingeressentialoilagainstmicroorganismsassociatedwithfoodis540clearlydemonstratedthroughinvitrostudies.
However,thedearthofliteratureonevaluationof541gingeressentialoilinfoodissurprising,comparedwithreportsonantimicrobialefficacyinfoodsof542essentialoilsfromotherplants[8,125]Apotentialapplicationofgingeressentialoilisthecontrolof543microorganismsonfreshandfresh-cutfruitsandvegetablesthatareintendedtobeconsumed544withoutacookingstep.
ShreddedgreenorunripepapayaisusedinseveraltypesofAsiancuisine,545includingThaipapayasalad.
Theabilityofthreeamountsofgingeressentialoil(5,10or15L)to546controlbacterial,mold,andyeastgrowthinshreddedgreenpapayastoredat13°Cfor4dayswas547evaluated.
Thepopulationsofbacteriaandyeastswereapproximately3-logloweronshreddedgreen548papayatreatedwiththehighestconcentrationofgingeressentialoilcomparedtotheuntreated549control.
Controlofmoldgrowthcouldnotbeevaluatedsincenoneofthepackagesexhibitedmold550growth[128].
RawpoultrycanbecontaminatedwithSalmonella,Campylobacter,orboth.
Often,551poultrycarcassesarerinsedorimmersedinawaterbathcontaininganantimicrobialchemical(e.
g.
,552chlorine).
Thepracticeisusedinparttoreducethemicrobialload,includingfoodbornepathogens,553onthecarcasspriortopackagingandshipmenttotheconsumer.
Utilizationofessentialoilstocontrol554Preprints(www.
preprints.
org)|NOTPEER-REVIEWED|Posted:16November2017doi:10.
20944/preprints201711.
0102.
v1Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
3390/molecules2212214516of23microorganismsonpoultrycarcasseswouldlikelybemetwithapositiveresponsebyconsumers.
555Chickenbreastandwholelegsampleswereimmersedfor2mininvariousconcentrationsofginger556essentialoil(1:150,1:250and1:550)andthentotalaerobicbacteria,E.
coli,S.
aureusandSalmonella557populationsdetermined[89].
Ahighlysignificantreductioninpopulationoftotalaerobicbacteria,E.
558coli,S.
aureusandSalmonellaoccurredfollowingtreatment.
Indeed,higherthana3-logreductionin559thepopulationsofE.
coliandSalmonellaonthesurfaceofchickenwasachieved.
Theseresultssuggest560gingeressentialcouldbeusedasanalternativetotraditionalantimicrobialchemicalsforthe561treatmentofpoultrycarcasses.
562Onwhatconcernssafetyissue,gingerisincludedamongspicesprovidedfromnaturalsources563generallyrecognizedassafe(GRAS)bytheAmericanFoodandDrugAdministration(FDA)[133].
564Fromclinicaltrials,wecanremarkwhichconcentrationscanbeconsideredofreasonablysafefor565humanconsumption.
Thedailydoseoforaladministrationofgingerrangedfrom500mg/dayto1000566mg/day;attheseconcentrations,adverseeffectswererareandmainlyinformofgastrointestinal567discomfort[85,92].
Consideringgingermetabolites(6-,8-and10-gingerolsand6-shogaols),aclinical568trialonhealthyvolunteersshowednotoxicityupto2000mg[134].
Atpreclinicallevel,usingrat569animalmodel,theacuteorallethaldoseofgingeressentialoilwasfoundover5g/kgofweight,and570certainteratogenicity,embryoniclossandmutagenicitycouldnotbedefinitelyruledout[135,136].
571Theresearchreportedontheefficacyofgingeressentialoiltoinactivateandcontrolmicrobial572populationsinvitroandinassociationwithfoodisencouraging.
Manymorestudiesshouldbe573completedusingessentialoilofgingerinoroncomplexfoodsbeforesolidconclusionscanbe574advancedwithrespecttoitsutility.
Thesestudiesshouldalsoevaluateorganolepticchanges575includingimpactontaste,odor,andcolor.
Akeyfactorinuseofgingeressentialoilasan576antimicrobialinfoodorfoodprocessingwillbecost.
Seismicshiftsinconsumerfoodpreferences577haveoccurredinrecentyears.
Consumeracceptanceoftheessentialoilofgingerasanalternativeto578traditionalfoodpreservativeswilllikelybemetwithenthusiasmevenifthecostoftheproduct579increasesslightly.
5805816.
Conclusions582Indian,Chinese,Japanese,Unanisystemsofmedicineusegingerextractstodealwithpainand583inflammatorydiseasesincedecades.
Attheendofthissurvey,,membersofthegenusZingiber584representapromisingandinnovativesourceofnaturalbioactiveagents,mainlygingerols,shogaols585andzingerone.
586Clinicalevidencesuggeststheirefficacy,inparticular,inmanaginghyperemesisrelatedto587pregnancyorchemotherapy.
Asantimicrobialagents,gingeressentialoilsappearespeciallyeffective588inthemanagementoffoodcontaminations,increasingshelflifeoffood.
Giventheirreasonablesafety589data,membersofthegenusZingibermayconstituteavalidalternativetowardscommondrugsto590managenauseaandvomiting,andtowardschemicalfoodpreservatives.
Thelatterissuemeetsthe591increasingconcernofconsumersawareofthepotentialhealthrisksassociatedwiththeconventional592antimicrobialsinfood.
593594AuthorContributions:Allauthorscontributedequallyinthepreparationofthemanuscript.
595ConflictsofInterest:Theauthorsdeclarenoconflictofinterest.
596597Preprints(www.
preprints.
org)|NOTPEER-REVIEWED|Posted:16November2017doi:10.
20944/preprints201711.
0102.
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v1Peer-reviewedversionavailableatMolecules2017,22,2145;doi:10.
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