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Research Article

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ARCHIVES OF CLINICAL MICROBIOLOGYISSN 1989-8436

iMedPub Journalswww.imedpub.com

DOI: 10.4172/1989-8436.100053

Loolaie M1#, Moasefi N2#, Rasouli H2* and Adibi H3

1 Department of Biology, Science and Research Branch, Islamic Azad university, Tehran, Iran

2 Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

3 PharmaceuticalSciencesResearchCenter, Kermanshah University of Medical Sciences, Kermanshah, Iran

# Thefirsttwoauthorshaveequallycontributioninthiswork

*Corresponding author: Hassan R

Hrasouli@kums.ac.ir, hadibi@kums.ac.ir

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah,Iran.

Citation: LoolaieM,MoasefiN,RasouliH, Adibi H (2017) Peppermint and ItsFunctionality:AReview.ArchClinMicrobiol.Vol.8No.4:54

Peppermint and Its Functionality: A Review

AbstractPeppermint (Mentha piperita L.), is a medicinal plant that has received moreattention from both food and pharmaceutical industries because of its healthbenefits for human society. Herein, the chemical structure of peppermintcompounds evaluated using theoretical studies. Indeed, the health benefitsof peppermint were reviewed. Our molecular docking showed that amongpeppermaint compounds, cineol and menthyl acetate apparently bound to the active site of arylamine N-acetyltransferase enzyme. This type of interactionindicatestheinhibitoryeffectsofthesecompoundsagainstthisenzyme.Quantumstudies revealed that menthol (Egap=16.9eV)andpulegone(Egap=12.6eV)arestableandunstablecompoundsinthisplant.Finally,ourtheoreticalresultsaresimilarto experimental investigations that reportedbefore. Summingup, this plant isagoodtargetforresearchandfurtherstudiesshouldbefocusonevaluatingofpeppermintinpreventionofhumandiseases.

Keywords: Peppermint; Human diseases; Peppermint oil; Quantum chemistry;Moleculardocking

Received: July 06, 2017; Accepted: July 31, 2017; Published: August05,2017

AbbreviationsPO: Peppermint oil; WHO:WorldHealthOrganization;HOMO:The highest occupied molecule orbital LUMO: The lowestun-occupied molecular orbital; MEP: Molecular electrostaticpotentials; NAT: Arylamine N- acetyltransferase; SD: Standarddeviation; IBS: Irritable bowel syndrome; HSV=Herpes simplexvirus(DNAvirus);VACV=Vacciniavirus

IntroductionMedicinal plants have receivedmoreattentionbecauseoftheirhealthbenefits,suchasanti-infectiousproperties,sinceancienttimes[1-6].Thetermofmedicalplantsisreferredtothenaturalremediesthathaveusedfortreatmentofhumandiseases[4,7-10]. These medicinal plants can be considered as a valuablesource of ingredientswhich can be used in drug development[5,11-13]. On the other hand, medical plants significantlyaffectedthehumanlifeacrosstheentireworld[5,7,14,15].Theuseofherbalmedicine is leadingmodality, followed inMiddleEast, Europe and certain other advance countries, in order to treat of catastrophic humandiseases [16]. Basedon theWHOreports, the advanced countries have used medicinal plant for bothclinicaltherapyandfoodindustriessignificantly[16,17].

Medicinalplantshavesignificantpotentialsforhumansocietiesandconsumedbypeopleacrosstheentireworld.Althoughmost

of theirhealthbenefitshavenotinvestigatedyet,theirmedicalactivitiescanbeconsideredinthetreatmentofpresentorfuturediseases[7].Currently,morethan80%oftheworldpopulationusethetraditionalmedicineandmedicinalplants(especiallyplantextractsandessentialoils) for theirprimaryhealthneeds [18].Peppermint or mint (Mentha piperita L.), a perennial aromaticherb belonging to the Lamiaceae (Labiatae) family, is a natural hybridbetweenspearmint (Mentha spicata L.)andwatermint(Mentha aquatic L.)[19,20].AlthoughitisanativegenusoftheMediterraneanregions,itcultivatedallovertheworldforitsuseinflavor,fragrance,medicinal,andpharmaceuticalapplications[21]. Members of the mint genus are characterized by theirvolatileoilswhichareofgreateconomicimportance,beingusedbytheflavor,fragrance,andpharmaceuticalindustries[22].

Thisplantiswidelyusedinfolkremediesandtraditionalmedicinefortreatmentofdigestivedisordersandnervoussystemactionsbecause of its antitumor and antimicrobial properties, chemo-preventive potential, its renal actions, antiallergenic effects,andalsoforlesseningcramping,digestivecomplaints,anorexia,

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nauseaanddiarrhea[23,24].Preparationsofpeppermintincludeleafs, leaf extracts andwater, however, the plant is cultivatedmainlyforitsessentialoil,whichisobtainedbydistillationfromfreshlygroundedleaves[25-28].POiscomposedofmentholandmenthone together with several other minor constituents,including pulegone, menthofuran and limonene, and its chemical compositionmayvarywithplantmaturity,geographical regionandprocessingconditions[28-30].

Mentholoccursnaturallyasacolorlesscrystalorpowder[31].Itisgreatlyresponsibleforthespasmolyticnatureofpeppermint[32].Mentholhasreportedtostimulatebileflow[33],reducingthe tone in the esophageal sphincter [34], facilitating belching[35],aswellashavingantibacterialproperties[36].Inaddition,peppermint is also a rich source of polyphenolic compounds and hencethestrongantioxidantproperties[8,22,26,28,37].Amongallcountriesintheworld,Indiaisthelargestproducer,exporter[38] and consumerofmintoil [39]. CurrentlyChina is amajorimporterofpeppermint[39].

HOMO(highestoccupiedmolecularorbital)andLUMO(lowestunoccupied molecular orbital) orbitals are very important parametersusedinquantumchemistry[40-42].Basedontheircharacteristics,itcanbespecifiedhowamoleculewouldinteractwithothermolecules[40].TheHOMOorbitalscanbeconsideredasanelectrondonorgroup,whiletheLUMOorbitalsasfreesitesabletoacceptthem[40,43-46].EnergyoftheHOMOorbitalscanbedirectlylinkedtotheionizationpotential,whereastheLUMOorbitalenergycanbeassociatedwiththeelectronaffinity[40,44].ThedifferencebetweentheorbitalenergiesofHOMOandLUMOis referred to as energy gap (ΔE)whichisanimportantparameterthatcandeterminethereactivityorstabilityofmolecules[40,44-46]. Since quantum chemistry and molecular docking studieshave not been reported, the present study aims at determining the optimized molecular geometry, HOMO-LUMO energies ofpeppermintmain compounds, usingHartree-Fock, 3-21Gbasicset and also indicates the binding mode of these compounds into aselectedreceptor.Also,themostabundantmedicinalbenefitsof peppermint have reviewed.

MethodsHereinthetherapeuticapplicationofvolatileoilofpeppermintis discussed and also chemical descriptors are calculated to determine the electron parameters of peppermint activeconstituentstosearchforbiologicalactivitiesofthesecompounds.

Molecular quantum studiesAll computational calculationswereperformedat theHartree-FockmodelonaPentium IV/2.8GHzpersonal computerusingSpartan 10 softwareWavefunction, Inc. [47]. The geometry ofthepeppermint active constituents in the ground state is fullyoptimized.

Molecular dockingThe3DstructureofNATenzyme(PDBID:2IJA)wasobtainedfromPDB database (http://www.rcsb.org/pdb/home/home.do) and selectedas receptor against peppermint chemical compounds.The molecular docking (blind docking) was done by Molegro

virtualDocker4.2.0version.Visualizationofdockingresultswasperformed by MOE software (https://www.chemcomp.com/MOE-Molecular_Operating_Environment.htm).

Nomenclature, botany and cultivationPeppermint hasmorethan101localnamesindifferentcountries(Table 1)[48-51].Theprincipleofnamingofmintisconsideredbasedonlocalcultureandcustoms.

In botany, Mentha piperita L.isthecommonnameforgenusofpeppermint [19]. The genusMentha includes 25 to 30 species[52]whichisaperennialherbandnativetoEurope,naturalizedinthenorthernUSAandCanada,andcultivatedinmanypartoftheworld[53,54].

The mint is a sterile hybrid of spearmint (Mentha spicata) and watermint(Mentha aquatica) from the Lamiaceae family (Figure 1)[20,27].

Themostrelevantofmintspecieswithcommercialormedicinalusage are listed in (Table 2).

Peppermint grows particularly well in lands with high water-holding capacity soil [55-70].All commercialmint varieties areseed sterile and are propagated using the underground stolons (runners or rootstock) produced by existing plants [71]. Thestolons can’t be stored for more than a few days since theydeterioraterapidlyduetoheatordehydration[71]. Ingeneral,mintstolerateawiderangeofconditions,andcanalsobegrowninfullsun[72].

Chemical properties Many studies showedthatpeppermintessentialoiliscomposedof various secondary metabolites [27,28,31,33,34,38,53,54,73,74]. Themint main chemical compounds consist of limonene, cineole, menthone, menthofuran, isomenthone, menthyl

Country Local nameIran Nanafelfeli

Brazil NortelapimentoUSA Lab Mint, mint

Norway PeppermyntePoland PepparmuntaSpain Mentainglesa

Portugal Hortelana pimentosaSwedish Pepparmynt

China Po HoIndia Urdu, mint, Pudina, Pudyana, PuthinaTurkey NanaRussia Myata perechnaya

Uruguay MentaFrench MentheIraq Nana

Bogota Yerba BeunaDenmark PebermynteGermany PeppermintEngland Brandy MintMexico Menta piperita

Table 1Themostabundantlocalnamesofmintaroundtheworld.

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acetate, isopulegol, menthol, pulegone and carvone (Figure 2 and Table 3)[38,74].

Other constituents include flavonoid glycoside (eg. Narirutin,Luteolin-7-o-rutinoside, Isorhoifolin and Hesperidin etc) [75]polyphenols (e.gRosmaricacid,Eriocitrin,Cinamicacid,Caffeicacid and Narigenin-7-oglucoside); luteolin-diglucoronide anderiodictyolglucopyranosyl-rhamnopyranosidewerealsopurifiedfromaerialpartsofmint[75-79].

The amount of peppermint compounds is different in variousspecies [80]. Various factors including physiological variations,environmental conditions, geographic differences and geneticfactorscausedifferencesinchemicalcompositionoftheseplants[80].

The most abundant chemical compounds that isolated form peppermint are largely classified into monoterpenes [81].Currently, peppermint is the best model system for the study of monoterpene metabolism [82]. The pathway of monoterpenebiosynthesis in peppermint has been well characterized by in vivo and systems biology studies (Figure 3) [83-85]. and all of

the enzymes involved have been described [81,84]. Accordingto the traditional view [86,87]monoterpenesareamongst themajor constituents of essential oils and common secondarymetabolites of plant metabolism, and as such they generally havebeenregardedasmetabolicdeadlock[83,84,87].Asshownin figure 3, the peppermint monoterpene-derived compoundsseparate from primary metabolism by conversion of isopentenyl diphosphateanddimethylallyldiphosphate,viatheactionoftheprenyltransferasegeranyldiphosphatesynthase(EC2.5.1.29),togeranyl diphosphate, which undergoes subsequent cyclizationbylimonenesynthase(EC4.2.3.16)to(4S)-(-)-limonene[84,88].In peppermint a microsomal cytochrome (Cyt) P450 limonene-3-hydroxylase (EC 1.14.13.47) adds an oxygen molecule in anallylic location to produce (-)-trans-isopiperitenol and therebyestablishestheoxygenationpatternofallsubsequentderivatives[81,88,89].

AsolubleNADP-dependentdehydrogenase(EC1.3.1.82)oxidizes

Figure 1 Aschematicillustrationofpepperminthybrid.

Mentha spicata Mentha aquatica

Mentha piperita

Species Usage ReferencesMentha spicata L. Medicine [55]

Mentha suaveolens OrnamentalConsumption [56]Mentha requienii Benth. OrnamentalConsumption [57]

Mentha pulegium L. Medicine [58]

Mentha piperita L. Medicine,Ornamentalconsumption,commercial

[59-61]

Mentha citrata Ehrh Medicine [62]Mentha longifolia L Medicine, Commercial [63,64]

Mentha cardiaca Medicine [65]Mentha arvensis Medicine [66]

Mentha canadensis Weed [67]

Mentha flavouring Ornamentalconsumption,Medicine [68,69]

Table 2Thelistofthemostabundantmintspeciesandtheirfunctions.

Figure 2 Representation of the most abundant chemicalcompoundsofPO.

Compounds IUPAC name Percentage(%) References

Limonene1-Methyl-4-(1-methylethenyl)-

cyclohexene1to5 [38]

Cineole 1,3,3-Trimethyl-2-oxabicyclo[2,2,2]octane 3.5to14 [23,76]

Menthone (2S,5R)-2-Isopropyl-5-methylcyclohexanone 14to32 [31]

Menthofuran 3,6-Dimethyl-4,5,6,7-tetrahydro-1-benzofuran 1to9 [23,28]

Isomenthone(2R,5R)-5-methyl-2-

propan-2-ylcyclohexan-1-one

1.5to10 [27]

Menthyl acetate

Aceticacid[(1R,2S,5R)-2-isopropyl-5-

methylcyclohexyl]ester2.8to10 [77]

Isopulegol 5-methyl-2-prop-1-en-2-ylcyclohexan-1-ol 0.2 [73]

Menthol (1R,2S,5R)-2-Isopropyl-5-methylcyclohexanol 30to55 [23,31,33,

38,49,53,77]Pulegone p-Menth-4(8)-en-3-one 4 [78]

Carvone 2-Methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one 1 [79]

Table 3 ThemostabundantactivecompoundsofMentha spp.

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chemistrycalculations[95,96].TheHOMOenergydeterminestheelectrondonatingabilitywhiletheLUMOdesignatestheelectronaccepting ability and the HOMO–LUMO energy gap () ( [97,98] is an important value for stabilityindex [96,99]. A large implies a good thermodynamic stabilityofthecompound,inthesenseofitslowerreactivityinchemical reactions [100,101]. However, the magnitude of theHOMO-LUMO gap has very important chemical implications,evenifqualitativelyevaluated[102].Todeterminestabilityandreactivity of peppermint main chemical compounds accordingto Hartree-Fock model 3-21G basis set calculation for watersolution,thegapenergiesweremeasured(Table 4).

Based on table 4 data, menthol, cineole and isopulegol havehigherstabilitythanothercompounds.Theincreaseofstabilitythat showed by promotes the low reactivity of thesecompounds in a chemical reaction. The relationship between

energy,stabilityandreactivityiswellknowndescribedinmanystudies[103-105].AccordingtoHartree-Fock,3-21Gbasicset calculation, the highest and lowest gap energies is relatedtomenthol(16.9eV),pulegone(12.6eV)andcarvone(12.6eV)respectively.Our result about stability ofmenthol is similar toresultthatreportedbyHarlodandcoworkers[106].Froehlichetal. reported that in the aqueous ethanolic solutions, pulegonewas unstable and it can be degraded to other products [107].Thiscaseconfirmedourmolecularorbitalsanalysisforpulegone.Also,surfacesforthefrontierorbitalsweredrawntounderstandthe bonding scheme of present compounds. The features ofthese molecular orbitals can be seen in (Figure 4).

the alcohol to a ketone, (-)-isopiperitenone, thereby activatingthe adjacent double bond for reduction by a soluble, NADPH-dependent,regiospecificreductasetoafford(+)-cis-isopulegone.An isomerase next moves the remaining double bond into conjugation with the carbonyl group, yielding (+)-pulegone. ANADPH-dependent reductase then converts (+)-pulegone to(+)-isomenthoneand(-)-menthone,whichpredominates[89].

Finally, two stereo-selective NADPH-dependent reductasesconvert (-)-menthone and (+)-isomenthone to (-)-mentholand (+)-neoisomenthol, respectively, and (-)-menthone and(+)-isomenthone to (+)-neomenthol and (+)-isomenthol,respectively[81,88,89].Inthesepathways,(-)-limoneneisthefirstcommittedintermediateforbiosynthesisofothercompoundsinthepeppermintspecies.However,productionofmonoterpenesin peppermint id restricted to developing oil glands of young leaves [88,90,91], and the correlationbetween in vitroactivityfortheseveralenzymaticstepsofmentholbiosynthesisandtherate of biosynthesis measured in vivo suggests that monoterpene productioniscontrolledbythecoordinatelyregulatedactivityofrelevantbiosyntheticenzymes[82,90,92].Asmentionedabove,(-)-Mentholgreatlyimportantamongthementholisomers(oftenexceeding50%oftheessentialoil)and isprimarilyresponsibleforthecharacteristicflavorandcoolingsensationofpeppermint[31,89,93,94].

HOMO and LUMO orbitals analysisTheHOMOandLUMOorbitals arevery important inquantum

Figure 3 Aschematicillustrationofmetabolicpathwayforbiosynthesisofpeppermintchemicalcompounds(ThepathwayistakenfromKEGGdatabase:http://www.genome.jp/kegg/).

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MEP analysisTheelectrostaticpotentialof amolecule is anestablished toolinmedicinalchemistry,modeling,andcomputationalchemistry[108,109]. The MEP employed abundantly for predictingpotentials have been and interpreting the reactive behaviorof a wide range of chemical system in both electrophilic andnucleophilic reactions, the study of biological recognitionprocesses and hydrogen bonding interactions [109-111]. Topredictreactivesitesforelectrophilicandnucleophilicattackforthe peppermint chemical compounds, MEP was calculated atHartree-Fock,3-21Gbasicsetoptimizedgeometries.Inthemostof theMEP,while themaximumnegative sitewhichpreferredregion for electrophilic attack indications as red color, themaximumpositive regionwhich preferred site for nucleophilicattacksymptomsasbluecolor[112,113].Inthepresentstudy,3Dplotofmolecularelectrostaticpotentialof studiedcompoundshasbeendrawnin(Figure 5).Inthisplotthedifferentvaluesofelectrostatic potential at surface are represented by differentcolors.Potentialincreaseinorderred<orange<yellowgreen<blue[113].

Asshownin(Figure 5),theregionshavingthenegativepotentialare over the electronegative atom oxygen, respectively. Thus,itwouldbepredicted thatanelectrophilewouldpreferentiallyattack peppermint compounds at the oxygen positions. Inaddition,wefoundthepositiveregionsoverhydrogenatomsofmethylgroupofpeppermintcompoundsandindicatingthatthesesitescanbethemostprobablyinvolvedinnucleophilicprocesses.Red and blue colors in peppermint compounds map refer to the regions of negative and positive potentials and correspond toelectron rich and electron-poor regions, respectively, whereasthegreenregionssignifytheneutralelectrostaticpotential.TheMEP surface map of peppermint compounds provides necessary informationabout reactivesites.Theseresultscanbeused fordesignanddevelopmentofthestablepeppermint-deriveddrugs.TheimportanceandapplicationofMEPmapindrugdevelopmentisdiscussedinmanystudies[114-117].

Antiviral ActivityNowadays, the development of phytotherapies aiming atthe inhibition of viral diseases [118], in combination with

classical anti-viral therapies, is among the most intensively studied approaches for the treatment of pathogenic viruses [119]. Infectiousviraldiseases remainan importantworldwideproblem, since many viruses have resisted prophylaxis or therapy longer than othermicroorganisms [120]. At themoment, onlyfeweffective antiviral drugs are available for the treatmentofviraldiseases[121].Thereisneedtofindnewcompoundswithnot only intracellular but also extracellular antiviral properties[122].Thereareseveralreportsshowedthatvariouspeppermintextracts has significant antiviral activities [123-126]. It seems,peppermint helps to immune system and protect the body from viruses [127-137]. Table 5 presents a comprehensive list of antiviruseffectofpeppermintextracts.

Antibacterial PropertiesMedicinal plants have been broadly used in common medicine and therefore, plant secondary metabolites are increasingly of interest as antimicrobial agents today [138,139]. Currently,biologically active compounds from peppermint sourceshave always been a great interest for scientists working oninfectious diseases [140]. PO and extracts showed a goodantimicrobialactivityagainst:1)Escherichia coli, 2) Salmonella pullorum, 3) Comamonas terrigena, 4)Streptococcus faecalis, 5)Acinatobacter sp, 6) Streptococcus thermophiles, 7) Lactobacillus bulgaricus, 8) Staphylococcus pyogenes, 9) Staphylococcus aureus, 10) Streptococcus pyogenes, 11) Serratia marcescens, 12) Mycobacterium avium, Salmonella typhi, 13) Salmonella paratyphi A/B, 14)Proteus vulgaris, 15)Enterobacter aerogenes, 16) Yersinia enterocolitica and 17) Shigella dysenteriae [131,141-143]. Studies showed that the antibacterial activityof peppermint leaves extract against Gram negative bacilliwashigher thanof its stemextract [131].Anumberofstudiesdemonstrated that essential oil from leaves of peppermintexhibited thehighest antibacterial activitywith 11.58 to 17.24mm±0.87SD,zoneofinhibition[1,62,125,133],whiletheeffectof extract obtained from the stem of peppermint is an average zoneofinhibition15.82mm±3.56SD,respectively[131].Ontheotherhand,POhasstronglyeffectsagainstEnterococcus faecium ATCC10541,Salmonella choleraesuis, Staphylococcus aureus and Bacillus subtilis[140-144]. Therearedifferencesinthechemicalcompositionofpeppermintessentialoil fromdifferentpartsofits structure [131]. As mentioned above, this differences canbeeffectonantibacterial activityof peppermint species [133].Generally, mint oil and menthol have moderate antibacterialeffects against both Gram-positive/negative bacteria [131].It seems peppermint can become a novel target for synthesis of plant-derived drugs against a large spectrum of multidrugresistance bacteria.

Antifungal ActivityIn-vitrodatasuggestedthatPOandextractsaregoodfungicidalagainst Candida albicans, Aspergillus albus and dermatophyticfungi[145].TheleaveoilsofMentha spicata exhibited moderate activityagainstAspergillus fumigatus (with16mm±0.5SD,zoneofinhibition)and A. niger (with14mm±0.5SD)[146].

Compounds HOMO(eV) LUMO(eV) (eV)Limonene -9.1 5.0 14.1

Cineole -10.1 6.3 16.4Menthone -10.6 4.2 14.8

Menthofuran -8.4 4.8 13.2Isomenthone -10.3 4.4 14.7

Menthyl acetate -11 5.0 16.0Isopulegol -9.7 5.0 14.7Menthol -10.9 6.0 16.9Pulegone -9.3 3.3 12.6Carvone -9.6 3.0 12.6

Table 4 HOMOandLUMOorbitalsenergyvaluesforpeppermintmainchemical compounds in water, calculated with Spartan 10 V1.1.0,software,Hartree-Fock,3-21Gbasicset.

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Figure 4 Theatomicorbitalcompositionofthemolecularorbitalofpeppermint-derivedcompounds.Forinterpretationofthereferencesto

colorinthisfigure,thereaderisreferredtothewebversionofthisarticle.

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Limonene Cineole Menthone

Menthofuran IsomenthoneMenthyl acetate

Isopulegol Menthol Pulegone

Carvone

Figure 5 Molecularelectrostaticpotentialsurfaceofpeppermintactivecompounds.(Forinterpretationofthereferencestocolorinthisfigure,thereaderisreferredtothewebversionofthisarticle).

Allelopathic EffectsAllelopathy isonekindof stress thatplaysa significant role inagro-ecosystems, and affects the growth, quality and quantityof the crops [147,148]. It was reported that water extract ofpeppermint (at concentration 10% v/v) is able to inhibits thegrowthofthetomatoseedlings[149].SkrzypekandCoworkers[150], demonstrated that aqueous extracts of peppermint (atconcentration 15% v/v) decreases non-photochemical and

photochemicalquenchingandvitalityindexofphotosystemIIinsunflower.

Medicinal Uses Currently,POhasbecomemostconsideredagentastreatmentforalargebodyofhumandiseases[38].ThemajorhealthbenefitsofPOareshownin(Figure6).Inadditiontomedicinaluses,itsextract isbroadlyusedasflavoring in food industries [151].Asmentionedinpervioussections,amongallchemicalcompounds

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thatpurified fromPO[31],menthol iscommon ingredientandwidely is used for respiratory congestion [152,153], headache[154],andskeletalmusclepain[155].ThebestdosageofPOforconsumption in adult was reported 0.2 to 0.4mL of oil threetimesdailyinenteric-coatedcapsules[156].

Anti-angiogenic/Inflammatory effectsAngiogenesis, the formation of new arterioles from pre-existingvessels, isamultistepevent involvingdegradationandremodeling of the underlying basement membrane and the surrounding extracellular matrix with subsequent proliferationand migration of vascular endothelial cells into the tissue tobe vascularized [157-159]. Inflammation is regarded as animportant baseline reaction responsible for manifestations ofvariouschronicdiseasessuchascancer,septicshock,diabetes,atherosclerosisandobesity[18,160].Recentdatahaveexpandedtheconceptthatinflammationisacriticalcomponentoftumorprogression [143]. There are several reports that peppermintcompoundshavecrucialrolesinpreventionofinflammationandangiogenesis [161-163]. Methanol extract of peppermint hascytotoxiceffectonL1210cancercells [164].Linandcolleagues[165]showedthatapparentlymenthol, inhigherdoses,effectsonNATactivity in the human liver tumor cell line J5 [166].TheNAT is responsible for thebiotransformationofnumerousarylaminedrugsand carcinogens [141]. This enzymehas threecritical residues consist of Cys68, His107 and Asp122 [167]. Theseresidues corresponding to active site of NAT enzyme [142].Herein,weperformedamoleculardocking tofind thebindingmodeofpeppermintcompounds intoNATenzymeasreceptor(Figure 7).

Docking results showed that cineole and menthyl acetateinteractwithHis107 residue and therefore, they are able to inhibit NATenzymeactivity (Figure 7A and 7C). Thedockingenergiesfor cineole, menthol, menthyl acetate, isopulegol, menthone and carvonewere -11.2, -13.4, -11.91, -9.82, -7.83 and -10.11kcal/mol, respectively. The His107 is one of critical residues intheactivesiteofNATenzymeanditisimportantforitsactivity[168].LinandCo-workers[165]reportedthatmentholapossibleuncompetitiveinhibitortoNATactivityincytosols.Ourdockingresultshowedthatmentholisabletointeractwithtworesidues(Tyr94 and Thr96) from NAT enzyme with a great probability(Figure 7B). In other hand,menthonwas also able to interact

Figure 6 ThemajorhealthbenefitsofPO.

Main Idea

Ulcer healing

Anti-spasmodic effects

Anti-bloat effects

Anti-lipid peroxidation

Anti-obesity

Anti-cancer

Anti-diabetic activity

Peppermintoil

Immunomodulation

Reducing irritable bowel syndrome

Reducing symptoms of non-ulcer dyspepsia

Anti-headache

Reducing gastrointestinal complications

Figure 7 Representation of peppermint compounds dockedwithNATenzymeasareceptor.(A)Cineole(B)Menthol(C) Menthyl acetate (D) Isopulegol (E) Menthone and (F)Carvone.

CineoleHis107

Menthol

Tyr94

Thr96

Menthyl acetate

His107

Gly124

Isopulegol

Thr289

A B

C D

Menthone

Tyr94

Thr96Carvone Gly124

E F

with these two residues from NAT enzyme (Figure 7E). Otherdocked compounds (i.e. isopulegol and carvone) interact withdifferentresiduesofreceptor(Figure 7D and 7F).

Antispasmodic effectsPO relaxes gastrointestinal smooth muscle [169] by reducingcalciuminfluxinbothlargeintestineandjejunum[170].POandmenthol are inhibitor for calcium channel activity in rats and

Extracts Virus References

Aqueous

HSV-1/2 [128,129]HIV-1 [130]

InfluenzaAvirus [131]Newcastlediseasevirus [132]

VACVinegg [132]SemlikiForest [133]

WestNileviruses [133]

AlcoholInfluenzaAvirus [134]

HSV [135]

EssentialoilHSV-1 [122,136,137]HSV-2 [122,137]

Table 5 Antiviralactivityofdifferentpeppermintextracts.

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guinea pig atrial and papillary muscle, rat brain synaptosomes, andchickretinalneurons[171,172].

Treating Irritable Bowel Syndrome IBS is defined as a chronic disorder of altered bowel functioncharacterized by symptoms of diarrhea, constipation, oralternatingbowelhabitsaccompaniedbypainordiscomfortandmay include a constellation of other symptoms, e.g., bloating,urgency, and incomplete evacuation [156,171,173-175]. Thissyndromeaffects9 to23%of thepopulationacross theworld[176].ItwasreportedthatPOisasafeandeffectiveshort-termtreatmentforIBS[177,178].Also,POactsasinhibitorforcalciumchannelactivityintheintestineandthereforeitcanabletoreducesymptomsof IBS [31].Otherpostulatedmechanisms forPO intreatmentofIBSincludeinhibitionofpotassiumdepolarization-inducedandelectricallystimulatedresponsesintheileum[179].Also, itwas reported that POhas crucial effects onhistamine,serotonin,andcholinergicreceptorsinthegastrointestinaltractmayalsomediatesomeofitsantiemeticeffects[180].Cappelloet al. showed that a fourweeks treatmentwith PO improvedabdominal symptoms in patients with IBS [181]. The similarresultsalsowerereportedinotherstudies[176,182-184].Takentogether, peppermint is the most encouraged plant for treatment ofgastrointestinaldisorders.

Anti-headache activitySinceancienttimes, herbal therapy has been used as treatment forheadachedisorders [185].Consumptionofpeppermintandderivativesisthebesttargetforheadachetherapy[186].Gobeletal.showedsomebenefitfrompeppermintandeucalyptusoilincombinationinrelievingpatients’headachepain[186].Also,similarresultwasreportedbyLevin[187].

Effect on hepatic enzymesMaliakal and Wanwimolruk reported that aqueous extract ofpeppermint (atconcentration2%v/v)canmodulateofphase IandphaseIIdrugmetabolizingenzymes[188].InphaseI,avarietyofenzymesacttointroducereactiveandpolargroupsintotheirsubstrates[189].PhaseIIbiotransformationreactionsgenerallyserveasadetoxifyingstepindrugmetabolism[190].Khodadustetal.showedthatpeppermintalcoholicextractamelioratedtheadverseeffectsofCCl4ongrowthperformanceandliverfunction,thereforetheyindicatedthatitmightbeusefulforthepreventionofoxidativestress-inducedhepatotoxicityinbroilers[191].

Radioprotective EffectsThe radioprotective activity of peppermint oil and aqueousextract has well been documented [192,193]. Kaushik et al.demonstratedtheeffectivenessofpeppermintalcoholicextractagainst radiation induced morbidity and mortality using theoptimum dose of 100 mg/kg for 3 consecutive days [192].Samarth and Coworkers suggested the antioxidant and free

radical scavenging activities of leaf extract of peppermint aredirectly relatedto itsmechanismof radiationprotection [193].Severalmechanismssuchasantioxidantactivity,immuneresponse,andenhancedrecoveryofbonemarrowhavebeensuggestedforchemopreventionandradioprotectionofpeppermintextracts[194].

Side Effects and ToxicityAlthough peppermint is a considered medicinal plant for treatment of humandiseases, itwas reported that in rats, POcausedcyst-likechanges inthewhitematterofthecerebellumand nephropathy at doses of 40-100mg/kg per day for 28-90days[195].

AdversereactionstoentericcoatedPOcapsulesarerare[174],but may include hypersensitivity reaction, contact dermatitis,abdominal pain, heartburn, perianal burning, bradycardia and muscletremor[175,196].

Inpatientswithchroniccough,pre-inhalationofmentholreducescoughsensitivitytoinhaledcapsaicinandinfluencesinspiratoryflows[197].Inrats,dosesof80and160mgofpulgeonefor28days caused atonia, weight loss, decreased blood creatininecontent,andhistopathologicalchangesintheliverandthewhitematterof thecerebellum[198].Mentholcauseshepatocellularchangesinrats[195].

MarketingThemarket forPO in theentireworld isdivided into localandinternational buyers. The local buyers included small buyersand companies from chemical and pharmaceutical, as wellas food and flavoring industries. The international buyers aredividedintoflavorandfragrancehouses,cosmeticsandpersonalhealthcare,aromatherapyandfoodmanufacturerswhobuyinlarge quantities [199]. The peppermint industry is the largestcommercialherbindustryintheUnitedStates(morethan4000tonsperyear).Keepinginviewmultiplebenefitsofpeppermint,various dosage forms are available inmarket for treatment ofvarious human lifestyle diseases (Figure 8).

Conclusion RemarksRegardingtohealthbenefitsofpeppermint,itcanbeconcludedthat this plant has great potentials for treatment of humandiseases and also it has strong future in theworldmarketing.Furtherstudiesareneedtoexplorationofcellularandmolecularmechanismsofpeppermintanditscompoundsonhumanbody.Althoughpeppermintplanthasgreatbeneficialandeconomicalrole in human society, researches must be considered its minor side effects and toxicity. The future in vivo human studies areneededtodeterminethemolecularmechanismofPOinhumanhealth.CurrentlyPOismostfrequentlytradedessentialoilintheentireworldandinmanydevelopedanddevelopingcountriesitconsideredasavaluabletargetforbothfoodandpharmaceuticalstudies.

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PO capsules

PO tabletes

PO gel and cr eams

Figure 8 DifferentdosageformsofPOaloneorincombinationwithotherchemicalingredientsareavailableinmarket.

AcknowledgmentHereby,theauthorswouldliketoexpresstheirgratitudetotheResearch Council of Kermanshah University of Medical Science (KUMS)fortheirsupportofthiswork.Also,wegratefullythankYoshihiro Kawaoka (editor in chief of Journal of Archives of

ClinicalMicrobiology)forhiskindinvitationtowritethecurrentmanuscript

Conflicts of InterestAuthorscertifythatnoactualorpotentialconflictofinterestinrelationtothisarticleexists.

References1 Nabavi SM,Marchese A, IzadiM, Curti V, DagliaM, et al. (2015)

Plantsbelongingtothegenusthymusasantibacterialagents:Fromfarmtopharmacy.FoodChem 173:339-347.

2 AkbariM,RasouliH,BahdorT(2012)Physiologicalandpharmaceuticaleffectoffenugreek:Areview.IOSRPHR2:49-53.

3 WangJ,YangD,WangZ,ChenB,YaoS(2009)Simultaneousofillegaladditivesindietarysupplementsandtraditionalmedicinesbyhigh

performance liquid chromatography–electrospray ionization massspectrometry.FoodChem113:227-232.

4 Xiao J (2016) Report of the international symposium onphytochemicalsinmedicineandfood.FoodChem204:497-498.

5 JaberianH, Piri K,Nazari J (2013) Phytochemical composition andin vitro antimicrobial and antioxidant activities of somemedicinalplants.FoodChem136:237-244.

6 Rezaie-Tavirani M, Fayazfar S, Heydari-Keshel S, Rezaee MB,Zamanian-Azodi M, et al. (2001) Effect of essential oil of rosa

2017Vol. 8 No. 4:54

ARCHIVES OF CLINICAL MICROBIOLOGYISSN 1989-8436

11© Under License of Creative Commons Attribution 3.0 License

damascenaonhumancoloncancercell linesw742.GastroenterolHepatolBedBench6.

7 HassanBAR (2012)Medicinalplants(importanceanduses).PharmAnalActa3:1000-1139.

8 WongCC, LiHB, ChengKW,Chen F (2006)A systematic surveyofantioxidantactivityof30 chinesemedicinalplantsusing the ferricreducingantioxidantpowerassay.FoodChem 97:705-711.

9 Rasouli H, Farzaei MH, Mansouri K, Mohammadzadeh S, Khodarahmi (2016) R Plant cell cancer: May natural phenolic compounds prevent onsetanddevelopmentofplantcellmalignancy?Aliteraturereview.Molecules21:1104.

10 Farzaei MH, Bahramsoltani R, Rahimi R, Abbasabadi F, Abdollahi (2016)MAsystematicreviewofplant-derivednaturalcompoundsforanxietydisorders.Curr.Top.Med.Chem16:1924-1942.

11 EdeogaHO,OkwuDE,MbaebieBO(2005)Phytochemicalconstituentsofsomenigerianmedicinalplants.AfrJBiotechnol 4:685-688.

12 daSilvaDX,deSouzaMW,CorrêaCdS,MoyaHD(2013)Acriticalstudyof use of the fe(ii)/3-hydroxy-4-nitroso-2,7-naphthalenedisulfonicacid complexes in the quantification of polyphenols in medicinalplants.FoodChem138:1325-1332.

13 Li Y, ZhouYC,YangMH,OuYangZ(2012)Naturaloccurrenceofcitrinininwidelyconsumedtraditionalchinesefoodredyeastrice,medicinalplantsandtheirrelatedproducts.FoodChem132:1040-1045.

14 Farnsworth NR, Akerele O, Bingel AS, Soejarto DD, Guo Z (1985)Medicinalplantsintherapy.BullWorldHealthOrgan 63:965.

15 Zamaninan Azodi M, Ardeshirylajimi A, Ahmadi N, Rezaee MB,JalilianFA,etal. (2013)Antibacterialeffectsofscrophulariastriataseedaqueousextractonstaphilococcusaureus.JPharmSci4:1-11.

16 AhmadR,AhmadN,NaqviA.A,ShehzadA,Al-Ghamdi(2016)M.S.Roleoftraditionalislamicandarabicplantsincancertherapy. J Tradit ComplementMed1-10.

17 Hong Kong S (2013) Traditional medicine strategy. World HealthOrganization:China20:113.

18 McKay DL, Blumberg JB (2006) A review of the bioactivity andpotential health benefits of peppermint tea (mentha piperita l.).Phytother Res 20:619-633.

19 Khalil AF, Elkatry HO, El Mehairy, HF (2015) Protective effect ofpeppermint and parsley leaves oils against hepatotoxicity on experimentalrats.Ann.Agric.Sci60:353-359.

20 Spirling LI, Daniels IR (2001) Botanical perspectives on healthpeppermint:More than just an after-dinnermint. J R Soc PromotHealth121:62-63.

21 Iscan G, KIrimer N, Kürkcüoglu Mn, Baser HC, DEMIrci F (2002)Antimicrobialscreeningofmenthapiperitaessentialoils.JAgriFoodChem 50:3943-3946.

22 DormanHD,KosarM,KahlosK,HolmY,HiltunenR(2003)Antioxidantproperties and composition of aqueous extracts from menthaspecies,hybrids,varieties,andcultivars.JAgriFoodChem51:4563-4569.

23 Keifer D, Ulbricht C, Abrams TR, Basch E, Giese N, et al. (2008)Peppermint (mentha xpiperita) an evidence-based systematicreviewbythenaturalstandardresearchcollaboration.JHerbMed 7:91-143.

24 SaeidniaS,GohariAR,YassaN,ShafieeA(2005)Compositionofthevolatileoilofachilleaconfertadc.Fromiran.DARU13:34-36.

25 Cosentino M, Bombelli R, Conti A, Colombo ML, Azzetti A, et al.(2009) Antioxidant properties and in vitro immunomodulatoryeffectsofpeppermint(menthaxpiperital.)essentialoilsinhumanleukocytes.JPharmSciRes1:33-43.

26 MairapetyanS,MamikonyanV,AlexanyanJ,TovmasyanA,DaryadarM(2016)Productivity,biochemicalindicesandantioxidantactivityofpeppermint (menthapiperita l.)andbasil (ocimumbasilicum l.) inconditionsofhydroponics.JAquacResDevelopment7:2.

27 UribeE,MarínD,VegGálvezA,Quispe-FuentesI,RodríguezA(2016)Assessmentof vacuum-driedpeppermint (menthapiperita l.) as asourceofnaturalantioxidants.FoodChem 190:559-565.

28 RiachiLG,DeMaria(2015)C.A.B.Peppermintantioxidantsrevisited.FoodChem176:72-81.

29 AnsariM, Vasudevan P, TandonM, Razda R (2000) Larvicidal andmosquito repellent action of peppermint (mentha piperita) oil.BiosciRep71:267-271.

30 Chen H, Zhong Q (2015) Thermal and uv stability of β-carotenedissolved in peppermint oil microemulsified by sunflower lecithinandtween20blend.FoodChem174:630-636.

31 Hawthorn M, Ferrante J, Luchowski E, Rutledge A, Wei X, et al.(1988) The actions of peppermint oil and menthol on calciumchannel dependent processes in intestinal, neuronal and cardiacpreparations.AlimentPharmacolTher2:101-118.

32 PeatJ,FrazeeC,KearnsG,GargU(2016)Determinationofmentholinplasmaandurinebygaschromatography/massspectrometry(gc/ms)205-211.

33 Arab Ameri S, Samadi F, Dastar B, Zerehdaran S (2016) Effect ofpeppermint (mentha piperita) powder on immune response ofbroilerchickensinheatstress.IranianJAppAnimSci6:435-445.

34 Oktemer T, Ipçi K,Muluk NB, Cingi C (2015) A pastille combiningmyrrh tincture, peppermint oil and menthol to treat the upperairway.ENTUpdates5:128.

35 BabaeianM, NaseriM, KamalinejadM, Ghaffari F, Emadi F, et al.(2016)Park JWTheefficacyofmentha longifolia in the treatmentof patients with postprandial distress syndrome: A double-blindrandomizedclinicaltrial.Iran.Red.Crescent19.

36 ChoiO,ChoSK,KimJ,ParkCG,KimJ(2016)Antibacterialpropertiesandmajor bioactive componentsofmenthapiperita essential oilsagainstbacterialfruitblotchofwatermelon.ArchPhytopathPlantProtect49:325-334.

37 LvJ,HuangH,YuL,WhentM,NiuY,etal.(2012)Phenoliccompositionandnutraceuticalpropertiesoforganicandconventionalcinnamonandpeppermint.FoodChem132:1442-1450.

38 AlankarS(2009)Areviewonpeppermintoil.AsianJPharmClin Res 2:27-33.

39 NairPS,RamanathanHN(2012)Thefutureofindianmint-astudytoforecastthemintexportsfromindia.JSCM1:10.

40 StachowiczJ,KrajewskaKułakE,ŁukaszukC,NiewiadomyA(2014)Relationship between antifungal activity against candida albicansand electron parameters of selected n-heterocyclic thioamides.‎IndianJPharmSci76:287.

41 AiharaJi(1999)Weightedhomo-lumoenergyseparationasanindexofkineticstabilityforfullerenes.Theor.Chem.Acc102:134-138.

42 RakhiR,SureshCH(2016)Adftstudyondihydropyrazineannulatedlinear polyacenes: Aromaticity, stability and homo–lumo energymodulation.Phys.Chem.Chem.Phys18:24631-24641.

2017Vol. 8 No. 4:54

12 This article is available from: www.acmicrob.com

ARCHIVES OF CLINICAL MICROBIOLOGYISSN 1989-8436

43 Janjua MRSA, Yamani ZH, Jamil S, Mahmood A, Ahmad I, et al.(2016)Firstprinciplestudyofelectronicandnon-linearoptical(nlo)propertiesof triphenylaminedyes: Interactivedesign computationofnewnlocompounds.AustJChem69:467-472.

44 Buyukuslu H, Akdogan M, Yildirim G, Parlak C (2010) Ab initiohartree-fockanddensityfunctionaltheorystudyoncharacterizationof3-(5-methylthiazol-2-yldiazenyl)-2-phenyl-1h-indole.SpectrochimActaMolBiomolSpectrosc75:1362-1369.

45 FukuiK(1982)Roleoffrontierorbitalsinchemicalreactions.Science218:747-754.

46 Yamaguchi K,HommaT,Nomi Y,Otsuka Y (2014)Characterisationofmaillard reactionproductsderived from lekfd–apentapeptidefound in β-lactoglobulin sequence, glycated with glucose – bytandemmass spectrometry,molecular orbital calculations and gelfiltration chromatography coupled with continuous photodiodearray.FoodChem145:892-902.

47 ShaoY,Molnar LF, JungY,Kussmann J,OchsenfeldC,etal. (2006)Advancesinmethodsandalgorithmsinamodernquantumchemistryprogrampackage.PhysChemChemPhys8:3172-3191.

48 Anjali J, Nardev SA (2016) Review on natural additives used incosmeticpreparations.WorldJPharmSci 5:630-648.

49 Rita P, Animesh DK (2011) An updated overview on peppermint(menthapiperital.).IntResJPharm 2:1-10.

50 Anonymous(2016)Mentha3:126.

51 Katzer G (2016) Peppermint (mentha piperita l). Journal ofPharmacology121.

52 HawryłM,NiemiecM,SłomkaK,Waksmundzka-HajnosM,SzymczakG (2016)Micro-2d-tlc separation of phenolics in some species ofmintandtheirfingerprintsondiolbondedpolarstationaryphase.ActaChromat28:119-127.

53 HockingGM,EdwardsLD(1955)Cultivationofpeppermintinflorida.Economic Botany 9:78-93.

54 KavrayanD,AydemirT(2001)Partialpurificationandcharacterizationof polyphenoloxidase from peppermint (mentha piperita). FoodChem 74:147-154.

55 Fitsiou E, Mitropoulou G, Spyridopoulou K, Tiptiri-Kourpeti A,Vamvakias M, et al. (2016) Phytochemical profile and evaluationof thebiological activitiesof essential oils derived from the greekaromaticplantspeciesocimumbasilicum,menthaspicata,pimpinellaanisumandfortunellamargarita.Molecules21:1069.

56 Wang J, Li R, Tan J, Jiang ZT ( 2016) Chemical composition ofessentialoil of grapefruitmint (mentha suaveolens×piperita) fromchina.JEssentOilBearPlant19:1047-1050.

57 Gaurav N (2016) An experimental text book on phytochemicalanalysisandantimicrobialactivityofmenthapiperita.Onlinegatha:

58 Nogueira MVC, de Lima Castro SAB, de Amorim AM, Maia RM,Paulillo LCMS ( 2016) Ethnobotanical survey of plants from the caatingawithpossibletherapeuticuses.Int.J.Curr.Microbiol.App.Sci5:767-772.

59 ÇobanÖ,BaydarNG(2016)Brassinosteroideffectsonsomephysicalandbiochemicalpropertiesandsecondarymetaboliteaccumulationinpeppermint(menthapiperital.)undersaltstress.IndCropsProd86:251-258.

60 MallickB,SinhaS,RoyD(2016)Evaluationofantioxidativepotentialoffieldgrownandtissueculturederivedmenthapiperital.Plants.IntJCurrMicrobiolAppSci5:382-391.

61 Gras A, Garnatje T, BonetMÀ, Carrió E,MayansM, et al.( 2016)Beyond food andmedicine, but necessary for life, too:Other folkplantusesinseveralterritoriesofcataloniaandthebalearicislands.JEthnobiolEthnomed12:23.

62 BokhariN,PerveenK,AlKhulaifiM,KumarA,SiddiquiI(2016)Invitroantibacterialactivityandchemicalcompositionofessentialoilofmenthaarvensislinn.Leaves.JEssentOilBearPl19:907-915.

63 MahmoudiR,KatiraeeF,TajikH, AbbasA (2016) Inhibitoryeffectofmentha longifolia l. Essentialoil against listeriamonocytogenesusingtransmissionelectronmicroscopy.IntJVetSciRes17:14-23.

64 Diop SM, Guèye MT, Ndiaye I, Hadji E, Fauconnier GL( 2016)Chemicalcompositionofessentialoilsandfloralwatersofmenthalongifolia(l.)huds.Fromsenegal.AmJEssentOilsNatProd4:46-49.

65 SajiN(2016)1-vinylcyclohex-3-enecarbaldehydeand4-vinylcyclohex-1-ene carbaldehyde for use in flavour and oral care composition.GooglePatents.

66 BhartiN,BarnawalD,ShuklaS,TewariSK,KatiyarR,etal.(2016)Integrated application of exiguobacterium oxidotolerans, glomusfasciculatum,andvermicompostimprovesgrowth,yieldandqualityofmenthaarvensisinsalt-stressedsoils.IndCropsProd83:717-728.

67 Yingying L, Haitao L, Xiaohua L, Lixia Z ( 2016) Diversity of tropical plant resources in yunnanprovince and its conservation. J LandscRes8:90-92.

68 NairB(2000)Finalreportonthesafetyassessmentofmenthapiperita(peppermint) oil, mentha piperita (peppermint) leaf extract, mentha piperita (peppermint) leaf, and mentha piperita (peppermint) leaf water.intJToxicol20:61-73.

69 Jenner P, Hagan E, Taylor JM, Cook E, Fitzhugh O (1964). Foodflavourings and compounds of related structure i.e. Acute oraltoxicity.FoodCosmetToxicol2:327-343.

70 Wraith JM, Robinson DA, Jones SB, Long DS ( 2005) Spatiallycharacterizingapparentelectricalconductivityandwatercontentofsurfacesoilswithtimedomainreflectometry. Comput Electron Agric 46:239-261.

71 Douhan, LI, Johnson D (2001) Vegetative compatibility andpathogenicityofverticilliumdahliaefromspearmintandpeppermint.PlantDis85:297-302.

72 MaffeiM(1999)Sustainablemethodsforasustainableproductionofpeppermint (mentha xpiperita l.) essentialoil. J EssentOil Res11:267-282.

73 ClarkR,MenaryR(1981)Variationsincompositionofpeppermintoilinrelationtoproductionareas.EconomicBotany35:59-69.

74 Rohloff J (1999) Monoterpene composition of essential oil frompeppermint (mentha×piperita l.) with regard to leaf positionusing solid-phase microextraction and gas chromatography/massspectrometryanalysis.JAgriFoodChem47:3782-3786.

75 AreiasF,ValentaoP,AndradeP,FerreresF,SeabraR(2001)Phenolicfingerprintofpeppermintleaves.Foodchem73:307-311.

76 Umezu T, Sakata A, Ito H (2001) Ambulation-promoting effectof peppermint oil and identification of its active constituents.Pharmacol.Biochem.Behav69:383-390.

77 Clark R, Menary R(1980) Environmental effects on peppermint(menthapiperital.).I.Effectofdaylength,photonfluxdensity,nighttemperatureanddaytemperatureontheyieldandcompositionofpeppermintoil.FunctPlantBiol7:685-692.

2017Vol. 8 No. 4:54

ARCHIVES OF CLINICAL MICROBIOLOGYISSN 1989-8436

13© Under License of Creative Commons Attribution 3.0 License

78 CroteauR,VenkatachalamK(1986)Metabolismofmonoterpenes:Demonstration that (+)-cis-isopulegone, not piperitenone, isthe key intermediate in the conversion of (−)-isopiperitenone to(+)-pulegoneinpeppermint(menthapiperita).AnnuRevPhysChem249:306-315.

79 MascherH,KikutaC,SchielH(2001)Pharmacokineticsofmentholandcarvoneafteradministrationofanenteric coated formulationcontaining peppermint oil and caraway oil. Arzneimittelforschung51:465-469.

80 ParkYJ,BaskarTB,YeoSK,ArasuMV,Al-DhabiNA,etal.(2016)Compositionofvolatilecompoundsandinvitroantimicrobialactivityofninementhaspp.Springerplus5:1628.

81 Gershenzon J, McConkey M.E, Croteau RB (2000) Regulation ofmonoterpeneaccumulation in leavesofpeppermint.PlantPhysiol122:205-214.

82 Mahmoud SS, Williams M,Croteau R (2004)Cosuppressionoflimonene-3-hydroxylase in peppermint promotes accumulation oflimoneneintheessentialoil.Phytochem65:547-554.

83 McGarveyDJ, CroteauR (1995) Terpenoidmetabolism. ThePlantCell7:1015.

84 Mahmoud SS, Croteau RB (2002) Strategies for transgenic manipulationofmonoterpenebiosynthesis in plants. Trends PlantSci7:366-373.

85 Rios-EstepaR,TurnerGW,LeeJM,CroteauRB,LangeBM(2008)Asystems biology approach identifies the biochemical mechanismsregulatingmonoterpenoidessentialoilcompositioninpeppermint.ProcNatlAcadSciUSA105:2818-2823.

86 BurbottAJ, LoomisWD (1969)Evidence formetabolic turnoverofmonoterpenesinpeppermint.PlantPhysiol44:173-179.

87 Tan XC, Chua KH, Ravishankar Ram M, Kuppusamy UR (2016)Monoterpenes:Novelinsightsintotheirbiologicaleffectsandrolesonglucoseuptakeandlipidmetabolismin3t3-l1adipocytes.FoodChem196:242-250.

88 Turner GW, Gershenzon J, Croteau RB (2000) Development ofpeltateglandulartrichomesofpeppermint.PlantPhysiol124:665-680.

89 McConkeyME, Gershenzon J, Croteau RB (2000) Developmentalregulationofmonoterpenebiosynthesisintheglandulartrichomesofpeppermint.PlantPhysiol122:215-224.

90 MahmoudSS,Croteau,RB(2003)Menthofuranregulatesessentialoil biosynthesis in peppermint by controlling a downstreammonoterpenereductase.ProcNatlAcadSciUSA100:14481-14486.

91 Turner G, Gershenzon J, Nielson EE, Froehlich JE, Croteau R(1999)Limonenesynthase,theenzymeresponsibleformonoterpenebiosynthesis in peppermint, is localized to leucoplasts of oil gland secretorycells.PlantPhysiol120:879-886.

92 LangeBM,MahmoudSS,WildungMR,TurnerGW,DavisEM,etal.( 2011)Improvingpeppermintessentialoilyieldandcompositionbymetabolic engineering. Proc.Natl. Acad. Sci.USA 108: 16944-16949.

93 FigueroaPérezMG,Rocha-GuzmánNE,Mercado-SilvaE,Loarca-Piña G, Reynoso-Camacho R(2014) Effect of chemical elicitorson peppermint (mentha piperita) plants and their impact on the metabolite profile and antioxidant capacity of resulting infusions.FoodChem156:273-278.

94 MortonC,GariochJ,ToddP,LameyP,ForsythA(1995)Contact

sensitivity to menthol and peppermint in patients with intra-oralsymptoms.ContactDermatitis32:281-284.

95 Chaitanya K (2012) Molecular structure, vibrational spectroscopic(ft-ir, ft-raman), uv–vis spectra, first order hyperpolarizability, nboanalysis, homo and lumo analysis, thermodynamic properties ofbenzophenone 2, 4-dicarboxylic acid by ab initio hf and densityfunctional method. Spectrochim. ActaMol Biomol Spectrosc 86:159-173.

96 EndoA, Sato K, Yoshimura K, Kai T, Kawada A,etal. (2011)Efficient up-conversion of triplet excitons into a singlet state anditsapplicationfororganiclightemittingdiodes.ApplPhysLett98:083302.

97 MillsNS,LevyA,PlummerBF(2004)Antiaromaticityinfluorenylidenedications.Experimentalandtheoreticalevidencefortherelationshipbetween thehomo/lumogapandantiaromaticity. JOrgChem69:6623-6633.

98 Cunha JD, Lavaggi ML, Abasolo MI, CerecettoH, GonzálezM(2011)2d-and3d-quantitativestructure-activityrelationshipstudiesforaseriesofphenazinen,n’-dioxideasantitumouragents.ChemBiolDrugDes78:960-968.

99 VennilaP,GovindarajuM,VenkateshG,KamalC(2016)Molecularstructure,vibrationalspectralassignments(ft-irandft-raman),nmr,nbo, homo-lumo and nlo properties of o-methoxybenzaldehydebasedondftcalculations.JMolStruct1111:151-156.

100 PrabavathiN,NiluferA,KrishnakumarV(2012)Molecularstructure,vibrational, uv, nmr, hyperpolarizability, nbo and homo–lumoanalysis of pteridine2, 4-dione. Spectrochim. Acta Mol BiomolSpectrosc99:292-302.

101 ZhouZ,ParrRG(1990)Activationhardness:Newindexfordescribingtheorientationof

102 electrophilicaromaticsubstitution.JAmChemSoc112:5720-5724.

103 Ruiz-Morales Y (2002) Homo-lumo gap as an index of molecularsizeandstructureforpolycyclicaromatichydrocarbons(pahs)andasphaltenes:A theoretical study. I. J. Phys.Chem.A 106:11283-11308.

104 ImH,KimS,ParkC,JangSH,KimCJetal.(2010)Highperformanceorganic photosensitizers for dye-sensitized solar cells. ChemCommun46:1335-1337.

105NakagawaT,KuSY,WongKT,AdachiC(2012)Electroluminescencebased on thermally activated delayed fluorescence generated bya spirobifluorene donor–acceptor structure. Chem Commun 48:9580-9582.

106 GoswamiS,AichK,DasAK,SarkarD,PanjaSA(2013)redfluorescence‘off–on’molecularswitchforselectivedetectionofal3+,fe3+andcr 3+: Experimental and theoretical studies along with living cellimaging.Chem.Commun49:10739-10741.

107 Nolen IH, FriendDR (1994)Menthol-β-d-glucuronide: A potentialprodrugfortreatmentoftheirritablebowelsyndrome.PharmRes11:1707-1711.

108 FroehlichO,ShibamotoT(1990)Stabilityofpulegoneandthujoneinethanolicsolution.JAgriFoodChem38:2057-2060.

109Wandtke CM, Lübben J, Dittrich B (2016)Molecular electrostaticpotentialsfrominvariompointcharges.Chem.Phys.Chem17:1-10.

110 KumarA,Gadre SR (2016) Exploring the gradient paths and zerofluxsurfacesofmolecularelectrostaticpotential. ‎J.Chem.TheoryComput12:1705-1713.

2017Vol. 8 No. 4:54

14 This article is available from: www.acmicrob.com

ARCHIVES OF CLINICAL MICROBIOLOGYISSN 1989-8436

111 PolitzerP,LaurencePR,JayasuriyaK(1985)Molecularelectrostaticpotentials: An effective tool for the elucidation of biochemicalphenomena.EnvironHealthPerspect61:191.

112 Arabi AA, Matta CF (2016) Electrostatic potentials and averageelectrondensitiesofbioisosteresinmethylsquarateandaceticacid.‎FutureMed.Chem8:361-371.

113 Tao Y, Han L, Li X, Han Y, Liu Z (2016) Molecular structure, spectroscopy (ft-ir,ft-raman),thermodynamicparameters,molecularelectrostaticpotentialandhomo-lumoanalysisof2,6-dichlorobenzamide.JMolStruct1108:307-314.

114 Balachandran V, Santhi G, Karpagam V, Revathi B, Karabacak M(2015) Spectroscopic investigation, natural bond orbital analysis,homo–lumoandthermodynamicfunctionsof2-tert-butyl-5-methylanisole using dft (b3lyp) calculations. Spectrochim. Acta Mol.Biomol.Spectrosc136:451-463.

115 PolitzerP, TruhlarDG (2013)Chemical applicationsof atomicandmolecularelectrostaticpotentials:Reactivity,structure,scattering,and energetics of organic, inorganic, and biological systems.SpringerScience&BusinessMedia.

116 Naray-SzaboG,FerenczyGG(1995)Molecularelectrostatics.ChemRev95:829-847.

117 BeckeA,MattaCF,BoydRJ(2007)Thequantumtheoryofatomsinmolecules:FromsolidstatetoDNAanddrugdesign.JohnWiley&Sons.

118Honig B, Nicholls A (1995) Classical electrostatics in biology andchemistry.Science268:1144.

119NawawiAA,NakamuraN,HattoriM,KurokawaM,ShirakiK(1999)Inhibitoryeffectsofindonesianmedicinalplantsontheinfectionofherpessimplexvirustype1.PhytotherRes13:37-41.

120 Fiore C, EisenhutM, Krausse R, Ragazzi E, Pellati D et al. (2008)Antiviral effects of glycyrrhiza species. Phytother Res 22: 141-148. Hall CB, Powell KR, MacDonald NE, Gala CL, Menegus MEet al. (1986) Respiratory syncytial viral infection in children withcompromisedimmunefunction.NEnglJMed315:77-81.

121 VijayanP,RaghuC,AshokG,DhanarajS,SureshB(2004)Antiviralactivityofmedicinalplantsofnilgiris.IndianJMedRes120:24.

122 Reichling J, Schnitzler P, Suschke U, Saller R (2009) Essential oilsof aromatic plants with antibacterial, antifungal, antiviral, andcytotoxicproperties–anoverview.Forsch16:79-90.

123 Brand YM, RoaLinares VC, BetancurGalvis LA, DuránGarcía DC,Stashenko E (2016) Antiviral activity of colombian labiatae andverbenaceae family essential oils and monoterpenes on humanherpesviruses.JEssentOilRes28:130-137.

124 SchuhmacherA,ReichlingJ,SchnitzlerP(2003)Virucidaleffectofpeppermint oil on the enveloped viruses herpes simplex virus type 1andtype2invitro.Phytomedicine10:504-510.

125 ShalayelM,AsaadA,QureshiM,ElhusseinA(2016)Anti-bacterialactivity of peppermint (mentha piperita) extracts against someemergingmulti-drug resistanthumanbacterial pathogens. JHerbMed22:152.

126 BekhitAE,ChengVJ,McConnellM,ZhaoJH,SedcoleRetal.(2011)Antioxidant activities, sensory andanti-influenza activityof grapeskinteainfusion.FoodChem129:837-845.

127 FleischnerAM(2001)Dietarysupplementsforeachspecificbloodtype.GooglePatents

128MoradiMT,Rafieian-KopaeiM,KarimiA(2016)Areviewstudyon

theeffectofiranianherbalmedicinesagainstinvitroreplicationofherpessimplexvirus.AvicennaJPhytomed20:1-11.

129 SantoyoS,JaimeL,García-RiscoMR,RodríguezA,RegleroG(2014)Antiviralpropertiesofsupercriticalco2extractsfromoreganoandsage.IntJFoodProp17:1150-1161.

130 GeuenichS,GoffinetC,VenzkeS,NolkemperS,BaumannI(2008)Aqueous extracts from peppermint, sage and lemon balm leavesdisplay potent anti-hiv-1 activity by increasing the virion density.Retrovirology5:1-16.

131 ShaikhS,YaacobHB,RahimZHA(2014)Prospectiveroleintreatmentofmajor illnessesandpotentialbenefitsasa safe insecticideandnaturalfoodpreservativeofmint(menthaspp.):Areview.AsianJBiomedPharm4:1.

132 AroraR,ChawlaR,MarwahR,AroraP,SharmaR(2010)Potentialof complementary and alternative medicine in preventivemanagement of novel h1n1 flu (swine flu) pandemic: Thwartingpotentialdisastersinthebud.JEvidBasedComplementaryAlternMed10:1-16.

133 SinghR,ShushniMM,BelkheirA(2015)Antibacterialandantioxidantactivitiesofmenthapiperital.ArabianJ.Geosci8:322-328.

134 Kunnumakkara AB, Chung JG, Koca C, Dey S (2009)Mint and itsconstituents. InMolecular targetsand therapeuticusesof spices:Modernusesforancientmedicine9:373-401.

135 ReichlingJ,NolkemperS,StintzingFC,SchnitzlerP(2008)Impactofethanoliclamiaceaeextractsonherpesvirusinfectivityincellculture.Forschende Komplementärmedizin/Research in ComplementaryMedicine15:313-320.

136 Edris AE (2007) Pharmaceutical and therapeutic potentials ofessential oils and their individual volatile constituents: A review.PhytotherRes21:308-323.

137 ShaabanHA,GhorabAH,ShibamotoT(2012)Bioactivityofessentialoilsandtheirvolatilearomacomponents:Review.JESSENTOILRES24:203-212.

138Mahboubi M, Kazempour N (2014) Chemical composition andantimicrobialactivityofpeppermint(menthapiperital)essentialoilSJST20:36.

139 AlmajanoMP,CarbóR,JiménezJAL,GordonMH(2008)Antioxidantandantimicrobialactivitiesofteainfusions.FoodChem108:55-63.

140Mucciarelli M, CamussoW,Maffei M, Panicco P, Bicchi C (2007)Volatile terpenoids of endophyte-free and infected peppermint(mentha piperita l): Chemical partitioning of a symbiosis.MicrobEcol54:685-696.

141 Bohnert T, Patel A, Templeton I, Chen Y, Lu C (2016) Evaluationof a new molecular entity as a victim of metabolic drug-druginteractions-anindustryperspective. ‎DrugMetabDisposdmd115:690-696.

142Rodrigues F, Dupret JM (2002) 3d model of human arylamine n-acetyltransferase 2: Structural basis of the slow acetylatorphenotypeofther64qvariantandanalysisoftheactive-siteloop.Biochem.Biophys.Res.Commun291:116-123.

143 SunZ,WangH,WangJ,ZhouL,YangP(2014)Chemicalcompositionand anti-inflammatory, cytotoxic and antioxidant activities ofessential oil from leaves ofmentha piperita grown in china. PloSone9:e114-767.

144 Saeed S, Naim A, Tariq P (2006) In vitro antibacterial activity ofpeppermint.PakJBot38:869.

2017Vol. 8 No. 4:54

ARCHIVES OF CLINICAL MICROBIOLOGYISSN 1989-8436

15© Under License of Creative Commons Attribution 3.0 License

145OumzilH,GhoulamiS,RhajaouiM,IlidrissiA,FaidMetal.(2002)Antibacterial and antifungal activity of essential oils of menthasuaveolens.PhytotherRes16:727-731.

146 Bansod S, Rai M (2008) Antifungal activity of essential oils fromindian medicinal plants against human pathogenic aspergillus fumigatusanda.Niger.WorldJMedRes3:81-88.

147GogaM,AntreichSJ,BačkorM,WeckwerthW,LangI(2016)Lichensecondarymetabolites affect growth of physcomitrella patens byallelopathy.Protoplasma20:1-9.

148 Shah AN, Iqbal J, Ullah A, Yang G, Yousaf M (2016) Allelopathicpotentialofoilseedcropsinproductionofcrops:Areview.EnvironSciPollutRes20:1-14.

149Mahdavikia F, Saharkhiz MJ (2016) Secondary metabolites ofpeppermint change the morphophysiological and biochemical characteristicsoftomato.BiocatalAgricBiotechnol7:127-133.

150 SKRZYPEK E, REPKAP, STACHURSKA SA, BARABASZ KB,MOŻDŻEŃK(2015)Allelopathiceffectofaqueousextractsfromtheleavesofpeppermint(mentha×piperita)onselectedphysiologicalprocessesofcommonsunflower(helianthusannuusl).NotBotHortiAgrobotClujNapoca20:43-48.

151 Ashurst PR (1991) Food flavorings. Springer Science & BusinessMedia19:151.

152 EcclesR(1994)Mentholandrelatedcoolingcompounds.JPharmPharmacol46:618-630.

153 EcclesR(2003)Menthol:Effectsonnasalsensationofairflowandthedrivetobreathe.CurrAllergyAsthmaRep3:210-214.

154Haghighi AB, Motazedian S, Rezaii R, Mohammadi F, Salarian L, et al. (2010) Cutaneous application of menthol 10% solution asan abortive treatment of migraine without aura: A randomised,double-blind,placebo-controlled,crossed-overstudy.IntJClinPract64:451-456.

155 PatelT,IshiujiY,YosipovitchG(2007)Menthol:Arefreshinglookatthisancientcompound.JAmAcadDermatol57:873-878.

156 KhannaR,MacDonald JK, LevesqueBG (2014)Peppermintoil forthetreatmentofirritablebowelsyndrome:Asystematicreviewandmeta-analysis.JClinGastroenterol48:505-512.

157WatsonEC,KoenigMN,GrantZL,WhiteheadL,TrounsonE,(2016)Apoptosis regulates endothelial cell number and capillary vessel diameter but not vessel regression during retinal angiogenesis.Development143:2973-2982.

158 Rasouli H, Mansouri K, Mahamed-Khosroushahi L (2014) Anti-angiogenic/inflammatory behavior of mushroom ganodermalucidum extract could be effective for treatment of cornealneovascularization:Ahypothesis.JRepPharmSci3:14-18.

159 RasouliH,ParvanehS,MahnamA,Rastegari-PouyaniM,HoseinkhaniZ,etal.(2017)Anti-angiogenicpotentialoftrypsininhibitorpurifiedfrom cucumis melo seeds: Homology modeling and molecular dockingperspective.IntJBiolMacromolec96:118-128.

160 Ku CM, Lin JY (2013) Anti-inflammatory effects of 27 selectedterpenoidcompoundstestedthroughmodulatingth1/th2cytokinesecretion profiles using murine primary splenocytes. Food Chem141:1104-1113.

161 KaeferCM,MilnerJA(2008)Theroleofherbsandspicesincancerprevention.JNutrBiochem19:347-361.

162 Yadav VR, Prasad S, Sung B, Kannappan R, Aggarwal BB (2010)

Targeting inflammatory pathways by triterpenoids for preventionandtreatmentofcancer.Toxins2:2428-2466.

163 KaleA,GawandeS,KotwalS(2008)Cancerphytotherapeutics:Roleforflavonoidsatthecellularlevel.PhytotherRes22:567-577.

164 Liu X, Sun Z-L, Jia A-R, Shi Y-P, Li R-H, et al. (2014) Extraction,preliminary characterization and evaluation of in vitro antitumorandantioxidantactivitiesofpolysaccharidesfrommenthapiperita.IntJMolSci15:16302-16319.

165 LinJ-P,LiY-C,LinW-C,HsiehC-L,ChungJ-G(2001)Effectsofmentholonarylaminen-acetyltransferaseactivityinhumanlivertumorcells.AmJChinMed29:321-329.

166 Deguchi T, Mashimo M, Suzuki T (1990) Correlation betweenacetylator phenotypes and genotypes of polymorphic arylamine n-acetyltransferaseinhumanliver.JBiolChem265:12757-12760.

167 Payton M, Mushtaq A, Yu TW, Wu LJ, Sinclair J, et al. (2001)Eubacterial arylamine n-acetyltransferases–identification andcomparisonof 18membersof theprotein familywith conservedactivesitecysteine,histidineandaspartateresidues.Microbiology147:1137-1147.

168Upton A, Johnson N, Sandy J, Sim E (2001) Arylaminen-acetyltransferases–of mice, men and microorganisms. TrendsPharmacolSci22:140-146.

169NissenL,LauE (2016)Olddrugnew indication:Antihistamineforthepaininyourstomach?AustralianPharmacist35:32-35.

170 SadraeiH,AsghariG,AlipourM(2016)Anti-spasmodicassessmentofhydroalcoholicextractandessentialoilofaerialpartofpycnocyclacaespitosaboiss.&haussknonrat ileumcontractions.ResPharmSci11:33-37.

171 Harris LA (2016) Treating irritable bowel syndrome: A fresh andmintyapproachtoanoldtherapy.DigDisSci61:334-336.

172 Jain PK, Das D, Jain P, Jain P (2016) Pharmacognostic andpharmacological aspect of bacopa monnieri-a review. Innovare JAyurvedicSci1:7-11.

173 CheyWD,Kurlander,J,EswaranS(2015)Irritablebowelsyndrome:Aclinicalreview.Jama313:949-958.

174 KlineRM,KlineJJ,DiPalmaJ,BarberoGJ(2001)Enteric-coated,ph-dependent peppermint oil capsules for the treatment of irritable bowelsyndromeinchildren.JPediatr138:125-128.

175 ReesW,EvansB,RhodesJ(1979)Treatingirritablebowelsyndromewithpeppermintoil.BMJ2:835-836.

176 Saha L (2014) Irritable bowel syndrome: Pathogenesis, diagnosis,treatment, and evidence-based medicine. World J Gastroenterol20:6759-6773.

177 Korterink JJ, Rutten JM, Venmans L, Benninga MA, Tabbers MM(2015)Pharmacologictreatmentinpediatricfunctionalabdominalpaindisorders:Asystematicreview.JPediatr166:424-431.

178 EganM,ConnorsEM,AnwarZ,WalshJJ(2015)Nature’streatmentforirritablebowelsyndrome:Studiesontheisolationof(−)-mentholfrom peppermint oil and its conversion to (−)-menthyl acetate JChemEduc92:1736-1740.

179 Sagduyu K (2002) Peppermint oil for irritable bowel syndrome.Psychosomatics43:508-509.

180 TateS(1997)Peppermintoil:Atreatmentforpostoperativenausea.J Adv Nurs26:543-549.

2017Vol. 8 No. 4:54

16 This article is available from: www.acmicrob.com

ARCHIVES OF CLINICAL MICROBIOLOGYISSN 1989-8436

181 Cappello G, SpezzaferroM, Grossi L, Manzoli L, Marzio L (2007)Peppermint oil (mintoil®) in the treatment of irritable bowelsyndrome: A prospective double blind placebo-controlledrandomizedtrial.DigLiverDis39:530-536.

182 Akehurst R, Kaltenthaler E (2001) Treatment of irritable bowelsyndrome:Areviewofrandomisedcontrolledtrials.Gut48:272-282.

183 Camilleri M, CHOI MG (1997) Review article: Irritable bowelsyndrome.AlimentPharmacolTher11:3-15.

184MadischA,HoltmannG,PleinK,HotzJ(2004)Treatmentofirritablebowelsyndromewithherbalpreparations:Resultsofadoubleblind,randomized, placebo-controlled, multicentre trial. AlimentPharmacolTher19:271-279.

185 LevinM(2012)Herbaltreatmentofheadache.Headache52:76-80.

186Gobel H, Schmidt G, Soyka D (1994) Effect of peppermint andeucalyptusoilpreparationsonneurophysiologicalandexperimentalalgesimetricheadacheparameters.Cephalalgia14:228-234.

187MaliakalPP,WanwimolrukS (2001)Effectofherbal teasonhepaticdrugmetabolizingenzymesinrats.JPharmPharmacol53:1323-1329.

188WolfKK,GuffordBT,BrantleySJ,WatkinsPB,PaineMF(2016)Drugmetabolism,transport.pharmacogenomics22:626-638.

189 Jancova P, Anzenbacher P, Anzenbacherova E (2010) Phase ii drug metabolizingenzymes.BiomedPapers154:103-116.

190 Khodadust MR, Asadi GH (2015) Effects of peppermint (menthapiperita l.) alcoholic extract on carbon tetrachloride-inducedhepatotoxicity in broiler chickens under heat stress condition.PoultrySciJ3:1-16.

191 KaushikP,MathurM,RawatN,DuttP(2012)Radioprotectiveeffectof alcoholicextractofmenthapiperita(linn)onswissalbinomiceexposedtowholebodygammairradiation:Apreliminarystudy.IntJPharmBioSci3:598-610.

192 Samarth RM, Panwar M, Kumar M, Kumar A (2006) Retracted:Radioprotectiveinfluenceofmenthapiperita(linn)againstgammairradiationinmice:Antioxidantandradicalscavengingactivity.IntJRadBiol82:331-337.

193 Kumar A, Samarth R, Yasmeen S, Sharma A, Sugahara T (2004)Anticancer and radioprotective potentials of mentha piperita.Biofactors22:87-91.

194GardinerP(2000)Peppermint(menthapiperita).LongwoodHerbalTaskForce1-22.

195NashP,GouldS,BernardoD(1986)Peppermintoildoesnotrelievethepainofirritablebowelsyndrome.BrJClinPract40:292-293.

196Millqvist E, Ternesten-Hasséus E, Bende M (2013) Inhalationof menthol reduces capsaicin cough sensitivity and influencesinspiratoryflowsinchroniccough.RespirMed107:433-438.

197 ShahPP,MelloP(2004)Areviewofmedicinalusesandpharmacologicaleffectsofmenthapiperita.NatProdRad3:214-221.

198MitchellAR,CroweFJ(1996)Peppermintoilyieldandcompositionfrommini and industrial distilleries. JHerbs SpicesMedPlants4:81-88.

199Matzat JH(1980)Thepeppermint industry:Situationandoutlookwithemphasisonoregon.Pharmacogenetics1-155.