w ww.e l s e v i e r . c o m / l o c a t e / b j p
Review
Antimicrobial
properties
of
the
mushroom
Agaricus
blazei
–
integrative
review
Cristiane
U.J.O.
Lima
a,
Eliana
F.
Gris
b,
Margô
G.O.
Karnikowski
a,b,∗aProgramadePós-graduac¸ãoemCiênciasdaSaúde,UniversidadedeBrasília,Brasília,DF,Brazil bFaculdadedeCeilândia,UniversidadedeBrasília,Ceilândia,DF,Brazil
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received26January2016 Accepted3May2016
Keywords: Agaricusblazei
Antibiotic Antimicrobial Antimicrobialagents Infection
a
b
s
t
r
a
c
t
Infectiousdiseasesassociatedwithantimicrobialresistanceareconsideredtorepresentanimportant publichealthproblem.Inthisregard,themushroomAgaricusblazeiMurrillcontainsseveralbioactive substancesthatpromotesignificantfunctionalproperties,amongthem,antimicrobialactivity,whichhas attractedtheinterestofthescientificcommunity.Thus,theaimofthisstudywastodeterminewhether evidenceoftheantimicrobialactionofA.blazeihasbeenreportedintheliterature.Inthisintegrative review,manuscriptsheldinresearchdatabasesavailableonlinewereexaminedwithaviewtoanswering thequestion“DoesthemushroomA.blazeiexertantimicrobialactivityagainstGram-negativeand/or Gram-positivebacteria?”Onlyeightscientificarticlesthathaveaddressedtheantimicrobialproperties ofA.blazei,invitroandinvivo,werefound,allcharacterizedaspre-clinical,i.e.,withlevelVIIevidence. MostauthorshavefoundthattheA.blazeiextractpromotesanantimicrobialeffectagainstperitonitis,as wellasdeadlyoralinfections,especiallythosecausedbyGram-positivebacteria.However,thescientific datacurrentlyavailablearenotsufficienttoverifytheantimicrobialaspectofthemushroomA.blazei andthusfurtherinvestigationisrequired.
©2016SociedadeBrasileiradeFarmacognosia.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Infectiousdiseaseshavebecomeamajorpublichealthproblem
worldwide.Inrecentyears,antibioticshavebeeninstrumentalin
therapyagainstinfectionscausedbyvariouspathogens(Huttner
etal.,2013).However,thereisanincreasingresistanceto
tradi-tionalantibioticsresultinginincreasedmorbidityandmortality,
prolongedhospitalstaysandincreasedhospitalcosts(Daveyand
Marwick,2008;Piddock,2012;Thabitetal.,2015).
Datashowthatapproximately70%ofthebacteriathatcause
hospital-acquiredinfectionsareresistanttoatleastoneofthedrugs
mostcommonlyusedforthetreatment(Lambertetal.,2010;Mertz
etal.,2015).Inmostcountries,thisriseinantimicrobialresistance
hasbeenfoundnotonlyinrelationtohospital-acquiredbutalso
community-acquiredinfections(OdonkorandAddo,2011;Abella
etal.,2015;Fistaroletal.,2015).
Theemergenceofantimicrobialresistanceisfacilitatedby
sev-eralfactors,whichare relatedtobacteriaorhumans.Antibiotic
resistance is related to particular aspects associated with the
∗ Correspondingauthor.
E-mail:margo@unb.com.br(M.G.Karnikowski).
overallprogressofbacteriaandthesecannotgenerallybe
inter-ruptedbyhumans,forinstance,themutationofbacteria,whichis
oneofthedeterminingfactorsofresistance(Licking,1999;Mah
andO’Toole,2001;StokesandGillings,2011;ArenzandWilson,
2016).However,theinadequateapplicationofdrugtherapywith
antibioticsinhumans,withalackofappropriatecriteriaor
incor-rectdose,treatmentperiod,activeagentetc.,candirectlyinfluence
thebacterialresistancetothistypeofdrug(Morganetal.,2011;
Meyeretal.,2013).
StudiessuggestthatthemushroomAgaricusblazeiMurrill,
cul-tivatedinBrazil,containsseveralbioactivesubstancesresponsible
foritsmedicinalproperties(Kasaietal.,2004;Kawamuraetal.,
2005;Ellertsen et al.,2006;Cordeiro and Bach, 2006;Smiderle etal.,2011;Firenzuolietal.,2007;Machadoetal.,2007;Hsuetal., 2008;Padilla et al.,2009; Jumeset al., 2010;Ishii et al.,2011; Carneiroetal.,2013;Uyanogluetal.,2014;Bertélietal.,2014),
notablyglucanswhich,inadditiontopromotingan
immunomodu-latoryresponse,caninduceanincreaseintheantimicrobialaction
ofthisfungus(Ohnoetal.,2001;Sorimachietal.,2001;Smyth
etal.,2002;Shimizuetal.,2002;Kanenoetal.,2004;Takimoto etal.,2004;Kasaietal.,2004;Kawamuraetal.,2005;Ellertsen et al., 2006; Yuminamochi et al., 2007; Smiderle et al., 2011).
Somestudiescarried outinanimalsand invitrohaveindicated
thatpro-inflammatorymediatorscaninducethephagocytosisof
http://dx.doi.org/10.1016/j.bjp.2016.05.013
StaphylococcusaureusandMycobacteriumtuberculosis,respectively (Riollet et al., 2000; Kisich et al., 2002). It hasbeen suggested
thattheinterpretationoftheseresultscouldbeextrapolatedto
A.blazeibecausethismushroompromotesthegrowthofvarious
cytokines,particularlypro-inflammatories.Thus, theserum
lev-elsresultingfromtheuseofchemokinesobservedinstudieson
A.blazei(Sorimachietal.,2001;Bernardshawetal.,2005;Ellertsen etal.,2006;Chanetal.,2007;Johnsonetal.,2009)couldenhance
thephagocytepowerofimmunecellsandpromotethe
effective-nessoftheresponsetoinfectionbypathogenicmicroorganisms.
Thesignificantincrease inthenumberof bacteriawhichare
resistanttoa broadspectrumantibiotics hasbecomeanurgent
publichealthproblemworldwide(WHO,2011;Kellyetal.,2016;
Khudaibergenova,2015).Considering therapidspread of
multi-drug resistance, the development of new antimicrobial agents
whichactonnewlyadaptedmicroorganismshasbecomea
prior-ity(Laxminarayanetal.,2013;Torjesen,2013).Someresearchers
havefocusedonthedevelopmentofantibioticsfromnatural
prod-uctsthatcancontrolinfectionwithoutencouragingtheemergence
ofresistantbacterialstrains(Gilbertetal.,2010; Sokovi ´cetal.,
2014).Mushroomscanbeconsideredasourceofnatural
antibi-oticsduetothepresenceofcertaincompoundsofinterest,suchas
terpenes,sesquiterpenes,steroids,anthraquinoneandderivatives
ofbenzoicacid,quinolines,oxalicacid,peptidesandproteins(Alves
etal.,2012).
Evenbeforetheadvent oftheresistanceofmicro-organisms
toconventionalantibiotics,therewasconsiderableinterestinthe
studyofnaturalproductsforthetherapeutictreatmentof
infec-tionspromotedbytheseorganisms.Inthiscontext,theaimofthis
reviewpaperistodeterminewhetherthereisscientificevidence
availabletosupporttheantimicrobialactionofthemushroomA.
blazei.
Methods
This study is characterized as an integrative review of the
scientific literature and the aim was to answer the
follow-ingquestion:“Does themushroomAgaricusblazeiMurrillexert
antimicrobialactivityagainstGram-negativeand/orGram-positive
bacteria”?
Thesurvey was conductedconsidering publications indexed
inthefollowing databases:BiremeLibrary,Cochrane,
Homeoin-dex, Lilacs, Pubmed/Medline, SciElo and ScienceDirect, using
‘antimicrobial agents’ as controlled descriptors and ‘medicinal
mushrooms’and‘AgaricusblazeiMurrill’asuncontrolled
descrip-tors. Thesedescriptors wereused in theirPortuguese language
versionsintheLilacsandSciElodatabases.Subsequently,areverse
lookupwasheldbyconsideringthereferencescitedinthearticles
researched.Scientificresearchpublicationsreportingthe
antimi-crobialaction ofthemushroomA.blazeiMurrill, inPortuguese,
EnglishorSpanish,regardlessoftheyearofpublication,adopting
anykindofmethod,weredefinedasinclusioncriteria.
DatawerecollectedduringtheperiodofSeptember–December
2014.Thedocumentswerefoundbywayofaliteraturereviewand
accessedincollectionsavailableonline.Theselectedarticleswere
readinfullforthepurposeoffurthercriticalanalysisand
catego-rization.Datarelatingtothejournal,authorandtypeofstudywere
alsoevaluated.Thestudieswerethencategorizedbasedonthelevel
ofevidence:Level1:systematicreview;Level2:randomized
clin-icaltrial;Level3:cohortstudy;Level4:case–controlstudy;Level
5:seriesofcases;Level6:expertopinion;Level7:pre-clinicaltrial
(invivo/invitro)asdescribedbyBork(2005).Theimpactfactorof
thejournalsinwhichtheresearchincludedinthisstudywas
pub-lishedwasidentifiedusingdatafromtheJournalCitationReports
(JCR).
Results
The total number of published manuscripts addressing the
antimicrobialactionofthemushroomA.blazeiwereeight,from
theyears1994–2014.Theimpactfactorsofthejournalsinwhich
thesepublicationsappeared,determinedfortheyear2014,ranged
from0.263to3.045(Table1).Regardingthecategoryofthe
stud-ies,accordingtothedesignadopted,itwasfoundthatallwere
pre-clinicaltrials;sevenperformedinvitroandtwoofthestudies
includedinthesamplegroupinvolvedresearchonanimals.Only
thestudybyBernardshawetal.(2005)involvedbothmethodscited
above,thatis,invivoandinvitro.Itshouldbenotedthatallinvivo
studieswerepredominantlycarriedoutonmice,withtheinclusion
ofacontrolgroupbesidesthetestgroup.
With regard to the types of A. blazei mushroom extracts
evaluated, it was observed that in two studies a commercially
available aqueous solution was evaluated, that is, AndoSanTM
(ImmunopharmaAS,Høvik,Norway)composedofA.blazei
mush-rooms(82%), Hericeumerinaceus(15%)andGrifola frondosa(3%)
(Bernardshawetal.,2005,2006).Theotherauthorsusedextracts
obtainedfrommushroomsinnatura,specificallythefruitingbodies
oftheBasydiomicetes,usingassolvents:hexane,chloroformand
methanol(Osakietal.,1994);waterandethanol(ZhuqiuandZhang,
2001);ethanol(Lundetal.,2009);methanol(Stojkovicetal.,2014.);
andwater(Sokovi ´cetal.,2014).Mazzuttietal.(2012)investigated
theuseofthesupercriticalfluidextractionprocesstoobtainthe
A.blazeiextractusingethanolasacosolventwithcarbondioxide
(CO2)andsubsequentlycomparedthismethodwithother
conven-tionalextractionprocedures(extractionbymacerationfollowedby
liquid–liquidpartition,hexaneandhydrodistillation)usingother
solvents,suchashexane,dichloromethane,ethylacetate,ethanol
andwater.
In studies which included animals in the sample group the
use of an orogastric intubation catheter was found to be the
administrationroutefortheA.blazeiextracts(Bernardshawetal.,
2005,2006).Therewasavarietyofmicroorganismstestedinthe
studiesanalyzed, witha predominanceof Gram-positive
bacte-ria:Salmonella typhi (Osakiet al.,1994); Staphylococcus aureus,
Bacillussabtilis,Escherichiacoli(ZhuqiuandZhang,2001); Strepto-coccuspneumoniaeserotype6Bpneumococus(Bernardshawetal.,
2005);coliforms (enterococci,a-hemolytic, hemolyticand
non-hemolyticstreptococci)(Bernardshawetal.,2006);oralmutans
streptococci(StreptococcusmutansUA159andStreptococcus
sobri-nus6715)(Lundetal.,2009);Staphylococcusaureus,Bacilluscereus,
EscherichiacoliandPseudomonasaeruginosa(Mazzuttietal.,2012);
Listeriamonocytogenes(Stojkovic etal.,2014);and P.aeruginosa
(Sokovi ´cetal.,2014).
Discussion
Thisresearchidentifiedthatthereiscurrentlyashortageofdata
obtainedfromscientificstudiesontheantimicrobialactionofthe
mushroomA.blazeiavailable.Thisfindingmaybeduetothe
impor-tanceofotherA.blazeiproperties,suchastheimmunomodulatory
andantitumorproperties,reflectinginthescientificliteratureand
increasinglypromptingresearcherstoverifythesefunctionswhen
adopting thevariousdesigns for theirstudies.It is noteworthy
thattherewasagreatdiversityofplaceswherethepublications
thatdealwithantimicrobialactivitywereperformed;however,the
Englishlanguagewaspredominant.ThevaluesfortheISIimpact
factorsofthejournalsinwhichthepublicationsappearedreveal
thatthereisqualityinthemethodologyemployedbytheauthors,
promotinga reduction in thebiaswhich couldinterferein our
Table 1
Distributionofmanuscriptsaccordingtotheidentification,typeofstudy,levelofevidence,publicationyear,journalfeaturesandantimicrobialactionofAgaricusblazei.
AntimicrobialactionAgaricusblazei Typeof
study/levelof evidence
Manuscript authors
Journal JournalCitation Reports(2014)
BactericidalactionagainstSalmonellatyphi. Preclinical study (ani-mals/invitro)
Osakietal., 1994
Yakugaku Zasshi
0.263
ExtractsofA.blazeiandaqueousethanol,didnotexercise antimicrobialactivityagainstthestrainstested(S.aureus,B. sabtilis,E.coli).
Preclinical study (ani-mals/invitro)
Zhuqiuand Zhang,2001
JournalFood Science
2.203
ProtectiveeffectagainstS.pneumoniae6Binfection(24hwhen administeredbeforeortogetherwiththeinoculation).No effectonantibioticpneumococciinvitro.
Preclinical study (ani-mals/invitro)
Bernardshaw etal.,2005
Scandinavian Journalof Immunology
1.739
Reductioninbacteremiaandincreasedsurvival(↓lethal septicemia)inmicewithfecalperitonitis.
Preclinical study (ani-mals/invitro)
Bernardshaw etal.,2006
Shock 3.045
Theethanolextract(100%)inhibitedthegrowthof
StreptococcusmutansUA159andStreptococcussobrinus6715 usingthediffusionmethodinagar.
IntestsofMICandMBC,thethreeextracts(50%,75%and 100%)hadantimicrobialproperties.
Preclinical study (ani-mals/invitro)
Lundetal., 2009
Pharmaceutical Biology
1.241
A.blazeiextractsobtainedfromlowpressuretechniques(using varioussolvents)aswellasbysupercriticalfluidextraction hadahigherantibacterialactivitytowardGrampositive bacteria(S.aureusandB.cereus).However,theextracts testedagainstGram-negativebacteria(E.coli,P.aeruginosa) canbeclassifiedasweakinhibitors.
Preclinical study (ani-mals/invitro)
Mazzuttietal., 2012
Thejournalof supercritical fluids
2.371
EthanolextractofA.blazeishowedgreaterantimicrobial activityagainstthegrowthofListeriamonocytogeneswhen comparedtoothermushrooms.
Preclinical study (ani-mals/invitro)
Stojkovicetal., 2014
FoodFunct 2.791
AqueousextractofA.blazeicausedasignificantreductionin virulencefactors(pyocyaninproduction,motility)and biofilmformationofPseudomonasaeruginosa.
Preclinical study (ani-mals/invitro)
Sokovi ´cetal., 2014
Molecules 2.416
MIC,minimalinhibitoryconcentration;MBC,minimalbactericidalconcentration;JCR,JournalCitationReports. ThearrowsindicatestimulationorinhibitionpromotedbyA.blazei.
Thecategorizationofallstudiesaspreclinicaltrials,together
withthesmallnumberofarticlespublishedinthescientific
litera-ture,suggeststhatthereisaneedformoreresearchtoaddressthe
antimicrobialfunctionofA.blazei,includingtheadoptionofother
methods,especiallyinvivotesting.
TheantimicrobialpropertiesofA.blazeihavebeenconfirmed
in most research studies using in vitro methods (Osaki et al.,
1994; Lundet al., 2009; Mazzutti et al., 2012; Stojkovic et al., 2014; Sokovi ´c et al., 2014) and in vivo testing mice, noting
thatinthis samplegroupthemushroomextractexertedaction
against microorganisms that cause lethal infections caused by
pneumococci (Bernardshaw et al., 2005) and fecal peritonitis
(Bernardshawet al., 2006).However, Zhuqiuand Zhang (2001)
found no antibacterial effects of A. blazei against four
differ-enttypes ofmicroorganismsanalyzedemployingtheminimum
inhibitory growth method. In addition, other researchers have
foundthattherewasnoantimicrobialeffectofA.blazeiusingan
invitromethod,althoughtheydidobservethispropertyinmice (Bernardshaw et al.,2005).The reason for the negativeresults
obtainedinthesetwostudiesisprobablybasedonthefactthatthe
antimicrobialmechanismofactionofbioactivesubstancespresent
inthemushroomrequiresengagementwiththeimmunesystem,
especiallytheinnateimmune system,which cannotbe
demon-stratedinvitro(Lulletal.,2005).
The results for research which confirmed the antimicrobial
activityofextractsof themushroomA. blazeimostly identified
greaterinhibitionfortheGram-positivebacteria(comparedwith
Gram-negativebacteria),suchas Salmonellatyphi,Streptococcus
pneumoniae,Streptococcusmutans,Streptococcussobrinus, Staphy-lococcusaureus,B.cereus,L.monocytogenesandcoliforms.Koneman etal.(1999)suggestthatthehypothesiswhichexplainsthesedata
isbasedonthestructuraldifferencespresentedbyGram-negative
microorganisms,suchasagreaternumberofflowpumpsorthe
presenceofanoutermembraneonthethinpeptidoglycanlayer
(Schweizer,2003;Listeretal.,2009;Breidensteinetal.,2011).
Thescientificevidenceobtainedfromallstudiesanalyzedin
this review is closely related to thetype of mushroom extract
adopted.Duetothesignificantinfluenceofcertain
environmen-talandmethodologicalfactors,thetypeandquantityofbioactive
constituents of A. blazei may vary according to the cultivation
method,climaticand soilconditions, useofraw ordehydrated
mushrooms,useofdryextract,typeofsolventextraction,
method-ologyemployedforthepreparationofthesolutionsandstorage
procedure(Daietal.,2010;Limetal.,2012;Montoyaetal.,2013).
Itisimportanttonotethatinthetwostudieswheretheinvivo
antimicrobialeffectofA.blazeiwasobserved(Bernardshawetal.,
2005,2006),acommercialaqueousextractwasusedasthereagent.
AlthoughthisproductiswidelyusedbytheJapanesepopulation,
thedescriptionofthechemicalcompositionofthisextractishighly
relevantinordertoidentifythepossiblecompoundsresponsible
fortheantibacterialpropertyandguidefutureresearch,andthis
wasnotcarriedoutinthestudiesinwhichitwasusedasareagent
(Stojkovicetal.,2013;Suetal.,2016).
Alveset al. (2012) conducted a review in order todescribe
the antimicrobial properties of extracts obtained from various
mushroomsandhighlightsomeoftheactivecompounds
identi-fied,includingcompoundsoflowandhighmolecularweight.The
researchersfoundthatmushroomshaveseveralantimicrobial
sub-stancesrepresentedbylowmolecularweightcompoundswhich
are mostly secondary metabolites, such as terpenes,
sesquiter-penesandothersteroids,anthraquinones,benzoicacidderivatives
andquinoline,aswellasprimarymetabolitessuchasoxalicacid.
However,peptidesandproteinsareconsideredtobethemajor
antimicrobial compounds of high molecular weight present in
mushrooms. Data in the literature indicate greater
However,inthisresearchthemushroomA.blazeiwasnot men-tioned.
Currently, it is well established in the literature that the
basiodimyceteA.blazeicontainsvariousbioactivecompoundsthat
promote a variety of functional properties, acting individually
and/orsynergistically.Thus,itisimportanttounderstandwhich
activesubstancesplayaroleintheantimicrobialaction.However,
thescientific literature doesnot provideinformation onwhich
bioactivecompoundinA.blazeiexercisesthisfunctionoronthe
mechanismofaction.However,amongthehypothesessuggested
byresearcherssomecompoundsarenotable,suchas-glucans
(Gonzagaetal.,2009;Yamanakaetal.,2012),antioxidants(Silva etal.,2009;Mourãoetal.,2011;Carvajaletal.,2012;Jiaetal., 2013;Hakime-Silvaetal.,2013;Wuetal.,2014),ergosterol(Zou, 2006;Gaoetal.,2007;HongandGu,2007;Hetlandetal.,2008;Shu
andLin,2011),tocopherol(Tsaietal.,2007),agaritine(Endoetal.,
2010),phenoliccompounds(Soaresetal.,2009)andnucleotides
andnucleosides(Oliveiraetal.,2010).
Someresearchershavesuggestedthattheantimicrobialaction
promotedbyA.blazeimushroomextractscanbeexplainedbased
onthepremisethat-glucansstimulatethesynthesisandsecretion
ofcytokinesbymacrophages(Sorimachietal.,2001),especiallythe
pro-inflammatorycompounds,andactivatethecomplement
sys-tem(Shimizuetal.,2002).A.blazeicontainasignificantamount
of-glucans(Hetlandetal., 2000;HetlandandSandven,2002;
Godshalletal.,2003)which,inadditiontostimulatingtheinnate
immunesystem,exertanantimicrobialeffect(Shinetal.,2005;
Chanetal.,2009).
Recently, Hetland et al. (2013) published a review which
aimedtocomparetheantimicrobialeffectsofthefollowingtypes
of polysaccharides: -glucans, pectin and commercial A. blazei
mushroomextract(AndoSanTM).Theseresearchersdemonstrated
that-glucansarepresentinthestructure ofyeastsand
mush-rooms and that pectin is present in Plantago major L., these
havinganti-infectionpropertiesinvariousmodelsofmiceagainst
microorganisms,includingbacteria.
The antimicrobial property of -glucans has been verified
invitroinmacrophagesinfectedwithM.tuberculosis(Hetlandand Sandven,2002)andinvivoinmiceinfectedwithMycobacterium bovis(Hetlandetal.,1998).The-glucanspromotethestimulation
oftheinnateimmunesystemthroughtheirconnectionwith
cer-tainspecificreceptorsonimmunecells,suchasToll-likereceptor2
(TLR2),dectin-1andCD11b/18.However,mushroomsmaycontain
molecularsubstances otherthan -glucans, whichcansimilarly
activateaninnateimmuneresponse(Dalonsoetal.,2015).
TheAndoSanTMextractcontainingA.blazei,aswellastwoother
typesofmushroom,initscomposition,hasbeenanalyzedintwo
studies (Bernardshaw et al., 2005, 2006), and its antimicrobial
actionhasbeenconfirmed.Thisisprobablyexertedbythe
mush-roomA.blazei,sinceitispresentingreaterquantityinthisextract
whencomparedtotheotherfungi.
Theprobablemechanismofactionassociatedwiththe
antimi-crobial effects of A. blazei mushroom extract (AndoSanTM) is
increased serum levels of pro-inflammatory cytokines MIP-2,
whichisequivalenttointerleukin-8(IL-8)inhumans,andtumor
necrosisfactor(TNF-␣)inmicethatreceivedA.blazeimushroom
extract(Bernardshawetal.,2005).Alternatively,this protective
effectcouldbepromotedbyA.blazei-mediatedinnateimmunity.
InastudybyBernardshawetal.(2006)usingamodelof
peri-tonitisinmiceitwasfoundthattheAndoSanTMextractexertedan
antimicrobialactionandtheresearcherssuggestedthatthe
mech-anismisbasedontheinhibitoryactionofTLR-4receptor-mediated
cellstimulationofNF-kBactivationviaTLR-2.Thismechanismmay
explaintheprotectiveeffectoftheextractinthismodelof
sep-sisinducedbyGram-negativemicroorganisms(Tryggestadetal.,
2013).
Accordingto Hetlandet al. (2013), this extract wasnotable
amongtheotherpolysaccharidesinvestigatedinthisstudy,that
is, -glucans and pectin, since it was more effective in terms
ofitsantimicrobialaction, basedonpreviouslyreportedresults
(Bernardshawetal.,2005,2006).
However,Sokovi ´c etal.(2014) hypothesizedthat the
mech-anism of action associated with the antimicrobial property
promotedbythemushroomA.blazeiisnotbasedonthestimulation
ofinnateimmunity,butcouldbeexplainedbytheinductionof
anti-quorum(anti-QS).Anti-QSdetectioncompoundshavebeenshown
todisrupttheformationofbiofilmsandconsequentlymakethem
moresusceptibletoantibioticbacteria.Thesecompoundsarealso
abletoreducethevirulencefactorofthebacteriaandpromotethe
eliminationofbacteriainanimalmodels(TaandArnason,2016).
OnestudyinvestigatedtheeffectofanaqueousextractofA.
blazei onthe virulence factorsof the quorumsystem (QS)and
biofilmformationagainstthebacteriumP.aeruginosa.Theresults
showthattheaqueousextractofA.blazeiexhibitedantibacterial
actionandalsoanti-quorumactivity.Theextracthadaneffecton
allmechanismstested,promotingareductioninbiofilmformation
andmotilityanddecreasingthesynthesisofpyocyaninpigment.
Theresearcherssuggestedthatthisdataobtainedfortheaqueous
extractofA.blazeimaybeusedforthepreventionand/orcontrol
ofthegrowthofP.aeruginosa(Sokovi ´cetal.,2014).
One of the substances present in A. blazei is linoleic acid
(Mazzuttietal.,2012),whichisconsideredtobeoneofthebioactive
componentsthatpromotethebactericidalactivityofthis
mush-room(FortesandNovaes,2006).Linoleicacidisconsideredtobe
anessentialunsaturatedfattyacid,becausethehumanbodydoes
nothavethebiologicalcapacitytosynthesizeit(Sanhuezaetal.,
2002).Thisfattyacidhasseveralfunctions,notablyreducingthe
serumlevelsoftriglyceridesandcholesterol,decreasingtherisk
ofallergies,cancerandatherosclerosisandantimicrobialactivity.
Theprobablemechanismofactionoftheantimicrobialactivity
pro-motedbythelinoleicacidistheabilityofthisfattyacidtobreakthe
membranesofbacterialcellsandcausecelllysis(Leeetal.,2002).
Ina recentstudytheantimicrobialactivityofphenolic
com-poundsfromdifferentspeciesofmushroomshasbeenidentified
and quantified. The researchers found that the phenolic
com-pounds2,4-dihydroxybenzoicacidandprotocatechuicacidhave
relativelyhighantimicrobialactivityagainstmostGram-negative
andGram-positivebacteria.Furthermore,inhibitionprovidedby
thephenoliccompoundswasgreaterthanthatoftheantibiotics
used for the treatment of infection promoted by
methicillin-resistantStaphylococcus aureus (MRSA).MRSA wasinhibitedby
2,4-dihydroxybenzoic,vanillic,syringic(MIC=0×5mgml−1)and
p-coumaric (MIC=1mgml−1) acid. Based on these results the
researchersconcludedthatthepresenceofcarboxylicacid(COOH),
twohydroxyls(OH),groupsintheorthopositionsofthebenzene
ringandalsoamethoxylgroup(OCH3)inthemetapositionappears
tobeimportantinrelationtotheanti-MRSAactivity(Alvesetal.,
2013).
Ontheotherhand,A.blazeicontainsavarietyofother
com-pounds, suchasergosterol(Takakuet al.,2001), othertypesof
fattyacids(Huangetal.,2011),polysaccharides(Huetal.,2015)
andalkalinesubstances (Ohnoet al.,2001)whichcanalsoplay
an importantrole in thesynergisticantimicrobial action.
How-ever, only one of the studies analyzed in this review reported
the isolation and identification of the bactericidal substance
13-hydroxy-cis-9,trans-11-octadecadienoic(13ZE-LOH)extracted
fromthefruitingbodyofA.blazeiusingchloroform-methanolasa
solvent(Osakietal.,1994).
Anotherissuetobeclarified,basedonscientifictheory,isrelated
to which route for the administration of the A. blazei extracts
employed favorsgreater absorptionofthe bioactivesubstances
thisregard,studiesbyBernardshawetal.(2005,2006)have
con-firmedthattheoraladministrationoftheA.blazeiextractinmice
promotedantimicrobialaction.However,somestudiesinhumans
(Johnsonetal.,2009;Limaetal.,2012)inwhichotherA.blazei
mushroompropertieswereevaluateddidnotidentifyanyeffect
whenadministeringtheextractofthisfungusorally.
Basedonthedatapresenteditappearsthatthereisstillnot
suf-ficientscientificevidencetosupporttheantimicrobialactionofA.
blazeimushroom.Thefavorableresultsobtainedinthemajorityof
invitroandinvivostudiesregardingthispropertyhaveattractedthe
interestofthescientificcommunityencouragingfurtherresearch.
Authors’contributions
Allauthorscontributedincollectingandanalyzingdatabesides
draftingparts of thepaper.All theauthorshave read the final
manuscriptandapprovedthesubmission.
Conflictsofinterest
Theauthorsdeclarenoconflictsofinterest.
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