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Abstract and Figures

Honey, propolis, bee pollen, bee bread, royal jelly, beeswax and bee venom are natural products which have been used in medicine since ancient times. Nowadays, studies indicate that natural bee products can be used for skin treatment and care. Biological properties of these products are related to flavonoids they contain like: chrysin, apigenin, kaempferol, quercetin, galangin, pinocembrin or naringenin. Several pharmacological activities of phenolic acids and flavonoids, and also 10-hydroxy-trans-2-decenoic acid, which is present in royal jelly, have been reported. Royal jelly has multitude of pharmacological activities: antibiotic, antiinflammatory, antiallergenic, tonic and antiaging. Honey, propolis and pollen are used to heal burn wounds, and they possess numerous functional properties such as: antibacterial, anti-inflammatory, antioxidant, disinfectant, antifungal and antiviral. Beeswax is used for production of cosmetics and ointments in pharmacy. Due to a large number of biological activities, bee products could be considered as important ingredients in medicines and cosmetics applied to skin.
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Molecules2020,25,556;doi:10.3390/molecules25030556www.mdpi.com/journal/molecules
Review
BeeProductsinDermatologyandSkinCare
AnnaKurekGórecka
1,
*,MichałGórecki
2
,AnnaRzepeckaStojko
2
,RadosławBalwierz
1

andJerzyStojko
3
1
SilesianAcademyofMedicalSciencesinKatowice,Mickiewicza29,40085Katowice,Poland;
radoslaw.balwierz@gmail.com
2
DepartmentofDrugTechnology,FacultyofPharmaceuticalSciencesinSosnowiec,MedicalUniversityof
Silesia,Jedności8,41200Sosnowiec,Poland;mgorecki@sum.edu.pl(M.G.);
annastojko@sum.edu.pl(A.R.S.)
3
DepartmentofToxycologyandBioanalysis,FacultyofPharmaceuticalSciencesinSosnowiec,Medical
UniversityofSilesia,Ostrogórska30,41200Sosnowiec,Poland;jstojko@sum.edu.pl
*Correspondence:akurekgorecka@interia.pl
AcademicEditors:RaffaeleCapassoandLorenzoDiCesareMannelli
Received:date;Accepted:date;Published:28January2020
Abstract:Honey,propolis,beepollen,beebread,royaljelly,beeswaxandbeevenomarenatural
productswhichhavebeenusedinmedicinesinceancienttimes.Nowadays,studiesindicatethat
naturalbeeproductscanbeusedforskintreatmentandcare.Biologicalpropertiesoftheseproducts
arerelatedtoflavonoidstheycontainlike:chrysin,apigenin,kaempferol,quercetin,galangin,
pinocembrinornaringenin.Severalpharmacologicalactivitiesofphenolicacidsandflavonoids,and
also10hydroxytrans2decenoicacid,whichispresentinroyaljelly,havebeenreported.Royal
jellyhasmultitudeofpharmacologicalactivities:antibiotic,antiinflammatory,antiallergenic,tonic
andantiaging.Honey,propolisandpollenareusedtohealburnwounds,andtheypossess
numerousfunctionalpropertiessuchas:antibacterial,antiinflammatory,antioxidant,disinfectant,
antifungalandantiviral.Beeswaxisusedforproductionofcosmeticsandointmentsinpharmacy.
Duetoalargenumberofbiologicalactivities,beeproductscouldbeconsideredasimportant
ingredientsinmedicinesandcosmeticsappliedtoskin.
Keywords:beeproducts;flavonoids,phenolicacids;skincare;therapeuticproperties
1.Introduction
Nowadays,alternativemedicine,whichemploysnaturalbiologicallyactivesubstancesobtained
frombeeproducts,isgettingmoreandmoreattention.Beeproductshavebeenusednotonlyin
treatment,butalsoforskincareasingredientsofcosmetics.Theeffectofbeeproductsontheskin
hasalsobeenprovedbynumerousstudies,andtheuseofhoney,propolis,beepollenandbeevenom
inwoundhealinghighlightstheircurativevalue[1–4].Eachbeeproductpossessesspecificactive
substanceswhichdetermineitsuseforvariousskinproblems.Honey,propolis,beepollen,beebread,
beeswaxandbeevenomarethebeeproductswhichareusedformedicinalpurposesandcosmetic
production.
Honeyisanaturalproductwhichismadebybeesfromnectarandhoneydew.Honeyisa
supersaturatedsolutionofcarbohydrateswithnumerouspropertiesandwideuse.Propolis,also
calledbeeglue,isaresinoussubstancecollectedbybeesfrombudsoftrees,shrubs,andgreenplants.
Both,propolisandhoneywereusedinantiquityforembalmingbodies,whereasfolkmedicineused
honeyforwoundhealingandpainrelief[5].
Beepolleniscollectedfromplantsandtransportedto
thehiveinformofpollenloads.Theformationofloadsinvolvesmoisturizingpollenwithnectaror
honey.Pollenforwintersupplies,whichisdepositedinthehoneycombcells,undergoeslactic
fermentationandproducesbeebread.Beebreadandbeepollenarebactericidalandbacteriostatic
agents[6,7].
Beeswaxisasubstanceproducedbyglandslocatedinthebeeabdomen.Waxobtained
Molecules2020,25,5562of17
fromhoneycombsconstitutesavaluableingredientusedincosmetologyandpharmacy.Beevenom
alsocalledapitoxinproducedbyhoneybee.Itconsistsacomplexmixtureofdifferentpeptidesand
mastcelldegranulatingpeptide,whichtherapeuticandcosmeticpropertiesareusedinmanyareas
[8].
2.SelectedCompoundsofBeeProducts
Thechemicalcompositionofbeeproductsisquitediversified,anddependsonthebotanical
composition,geographicalorigin,timeofcollectionandenvironmentalconditions[9–11].However,
eachproductmadebybeeshasaspecifiedcompositionandcontentofbiologicallyactivesubstances,
whichgivespecificpropertiestoeachbeeproduct.Thechemicalcompositiondeterminesthecurative
andpropertiesoftheseproducts.
Honeycontainsatleast181ingredients[12].Honeyisasupersaturatedcarbohydratessolution
containingmainlyglucoseandfructose[13].Moreover,honeycanhaveinitscompositionofsucrose,
rhamnose,trehalose,nigerobiose,isomaltose,maltose,maltotetraose,maltotriose,maltulose,
melezitose,melibiose,nigerose,palatinose,raffinose,anderlose[14,15].Italsocontainsenzymes,
namely,glucoseoxidase,amylase,catalase,peroxidase,invertase,andlysozyme.Glucoseoxidase
produceshydrogenperoxidewhichisoneofresponsiblesubstancesforthebactericidalactivityof
honey[16].Honeycontainsalsoorganicacids:gluconicacid,citricacid,malicacid,lacticacid,
succinicacid,oxalicacid,tartaricacid,formicacid,aceticacid,benzoicacid,andpyromucicacid.The
acidsoriginatefrombeebodiesandenzymaticconversionswhichoccurduringhoneyproduction.
Thecontentoftheseacidsishigherinmaturehoneys.Phenolicacidsandflavonoids,whichare
responsibleformanybiologicalpropertiesandhaveantioxidativeactivity,arealsoimportant
ingredientsofhoney.Thegroupofphenolicacidsincludesderivativesofhydroxycinnamicacidand
hydroxybenzoicacid.Thederivativesofhydroxycinnamicacidarepcoumaricacid,caffeicacid,
ferulicacid,andsinapicacid.Whereas,thederivativesofhydroxybenzoicacidincludep
hydroxybenzoic,vanillic,syringic,salicylicandgallicacidsandellagicacidasadimerofgallicacid
[15].Inhoney,flavonoidsarerepresentedbynaringenin,hesperetin,pinocembrin,chrysin,galangin,
quercetinandkaempferol.However,asignificantdecreaseintheconcentrationofgalangin,
kaempherol,andmyricetinisobservedafterhoneyhasbeenheated,whilepasteurizationcausesa
substantialdecreaseinmyricetinconcentration[17].Honeycontainsalsoessentialoils,whose
compositionincludesterpenes(thymol,bisabolol,farnesol,andcineol).Othercomponentsofhoney
comprisewater,aminoacidsandproteins.Proline(50–80%)dominatesamongaminoacids,andits
increasedpresenceindicateshoneymaturity[14].Vitaminsconstituteasmallgroupofcompounds
presentinhoney,andtheyaremainly:thiamine,riboflavin,pyridoxine,paminobenzoicacid,folic
acid,pantothenicacid,andvitaminsA,C,E.Honeycontainsalsominerals:phosphorus,potassium,
calcium,magnesium,sulfur,iron,copper,manganese,andzinc.Althoughthereisonlyasmall
amountoftraceelementsinhoney,theyarehighlybioavailable.Itwasreportedthatcopper,calcium,
zinc,iron,manganeseandmagnesiumfromhoneyarecharacterizedabioavailabilityof80–90%[18].
Intermsofchemicalcomposition,propolisisaverydiverseproduct.Atpresent,atleast300
activecompoundshavebeenidentifiedinit[19].Phenolicacids(caffeic,ferulic,chlorogenic,p
coumaric),benzoicacid,cinnamicacidandflavonoidsarethemostimportantbiologicallyactive
compounds.Amongflavonoids,wecanenumeratechrysin,luteolin,apigenin,galangin,kaempherol,
quercetin,pinostrobin,pinocembrin,andterpenecompounds,whosecontentis0.5%(bisabolol),and
alcohols(cetyl,myricyl,mannitolandinositol)[20–22].Propoliscontainsalsominerals(calcium,
magnesium,manganese,zinc,copper,iron,cobaltandselenium),vitamins(B1,B2,B6,CandE)and
enzymes(succinatedehydrogenase,glucose6phosphatase,adenosinetriphosphatase,acid
phosphatase)[22,23].
Beepollencomprisesatleast200biologicallyactivesubstances.Proteinsconstituteabout22.7%
ofbeepollencomposition,including10.4%essentialaminoacids:methionine,lysine,threonine,
histidine,leucine,isoleucine,valine,phenylalanine,tryptophan.Digestiblecarbohydratesconstitute
30.8%,whilethepercentageofreducingsugarsis25.7%.Amongthefattyacidspresentinbeepollen,
wecanlistacidssuchasgammalinolenicacid,arachidonicacid,andlinoleicacid(0.4%).
Molecules2020,25,5563of17
Additionally,nucleicacidsandnucleosidesarevaluablecomponentsofbeepollen[2,24].Itcontains
alsovitamins(B1,B2,B3,B5,B6,C,H,E)andminerals(potassium,calcium,phosphorus,iron,zinc,
copper,manganese)[9].
Proteincontentinbeebreadis12%lowerthanitscontentinbeepollen.Thecontentofreducing
sugarsincreasesby40–50%,whereasthecontentoflacticacidrisesto3.1%.Beebreadcontains
vitaminKandenzymeswhichcannotbefoundinbeepollen[25,26].Beebreadisalsoagoodsource
ofphenoliccomponents.AmongbeebreadfromdifferentpartsoftheBalticRegionthepcoumaric
acid,ferulicacid,caffeicacid,kaempherol,isorhamnetin,naringeninandquercetinwereidentified
[27].
Royaljellycontainspeptides:jelleinesI,II,III,IV,proteins,carbohydrates,lipids,vitaminsand
minerals[28].Amongproteinswecanlistroyalisinandenzymes:amylase,invertase,catalase,acid
phosphatase,andlysozyme.Proteinsofroyaljellyarerichinexogenousaminoacids.The
carbohydratesinroyaljellyaremainlymonosaccharides:fructose,glucoseandoligosaccharides.
Lipidsplayanimportantroleinroyaljellycomposition[29].10hydroxytrans2decenoicacid,3
hydroxydodecanoicacid,and11oxododecanoicacidcanbeincludedintothemostvaluableones
[28].10hydroxytrans2decenoicacid(10H2DA)isthemainandspecificlipidcomponentofthis
product.10H2DAisusedasamarkertovalidatethequalityofroyaljelly[28,30].Royaljellycontains
alsovolatilecompoundssuchasphenol,guaiacolandmethylsalicylate.Inroyaljelly,therearealso
presenttraceamountsofsuchbioelementsaspotassium,sodium,magnesium,phosphorus,sulfur,
calcium,zinc,iron,andcopper.RoyaljellycontainsmainlyvitaminsfromgroupB:thiamine,
riboflavin,pyridoxine,pantothenicacid,nicotinicacidandbiotinanditisalsocontainsphenolic
compounds:ferulicacid,quercetin,kaempherol,galanginandfisetin,pinocembrin,naringinand
hesperidin,apigenin,acacetin,andchrysin[31,32].
Estersofacidsandfattyalcoholsaremainconstituentsofbeeswaxandsubsequentcomponents,
inrespectofamount,arefreefattyacids[33].Amongthelatter,10hydroxytrans2decenoicacid
(10H2DA)exhibitsantibacterialeffect,whichisimportant.Beeswaxiscomposedofhydrocarbons
andfreefattyalcohols[34,35].Freefattyalcoholssuchastriacontanol,octacosanol,hexacosanol,and
tetracosanolareantioxidativeandantiinflammatory.Othersubstancesaretriterpenes,βcarotene,
volatilecompoundsandphenoliccompounds.Amongflavonoids,themainroleisplayedbychrysin,
whichrelievesinflammation,hasantimicrobialandregenerativeeffects.Sterolshavearegenerative
effect,whereasanantisepticeffectisprovidedbythreecomponents:10hydroxytrans2decenoic
acid,chrysin,andsqualene[34,36].
Beevenomcontainsdifferentpeptidesincludingmelittin,apamine,adolapin,sekapin,
prokaminandmastcelldegranulatingpeptide[37].Peptidesaremaincomponentsofbeevenom.
Amongpeptidesespeciallymelittinplaysimportantroleininducingreactionsassociatedwithbee
stings.Melittininducesmembranepermeabilizationandlysescells.Itpossessesalsobiologically
activeamineslikehistamine,epinephrine,dopamine,norepinephrineandenzymeslike
phospholipaseA2,hyaluronidase,acidphosphomonoesterase,lysophospholipase.Beevenomhas
anothercomponentsthanpeptidesincludinglipids,carbohydratesandfreeaminoacids[8,38,39].
3.BeeProductsasRawMaterialforMedicinesandCosmeticsProduction
Honeyincosmeticsisnamed“Honey”or“Mel”accordingtotheInternationalNomenclatureof
CosmeticIngredient(INCI),itisanemollientorhumectant,andexhibitsmoisturizingproperties.
Somecosmeticscontainderivativesofhoney,definedintheINCIas“MelExtract”withmoisturizing
properties,“HydrogenatedHoney”whichishumectant,andantistatic“Hydroxypropyltrimonium
Honey”.Hydroxypropyltrimoniumhoneyisusedinshampoosandhairconditioners.Moreoftenthe
concentrationofhoneyincosmeticsisupto10%.Higherconcentrations(upto70%)areobtainedby
dispersinginoils,gelsorpolymerentrapment[40].
Mostfrequently,propolishasaformofaqueousorethanolextracts.AccordingtotheINCI
nomenclature,incosmeticswecanfinditunderthefollowingnames:propolisandpropolisextract.
Ethanolextractsofpropolisaremostfrequentlyused.Toobtainthem,propolisisextractedwith70%
ethanol,andthentheextractisconcentratedinreducedpressureconditions[41].Anaqueousextract
Molecules2020,25,5564of17
ofpropolisisusedinantifungalcosmetics,whilepropolisdissolvedinfatsisusedtoproduce
lipsticks.
Royaljellycanmostfrequentlybefoundincosmeticsinalyophilizedform,andthehigher
percentagecontentoflyophilizedroyaljellyis,thelessviscouscreambecomes.However,royaljelly
contentdoesnotaffectemulsionstability.Preparationswithahighercontentofroyaljellyarewell
absorbed,anddonotleavegreasyfilm.Creamswithroyaljellyhavemoisturizingproperties
especiallyinconcentrationof0.5%and1%[42].
Incosmeticmanufacturing,beepollenisusedinaformofaqueous,lyophilizedandlipid
extracts.Activesubstancescanbeextractedwithwater,propyleneglycols,glycerinandoils.Bee
pollenextactsareusedincosmeticinconcentrations0.5–5%[43].Innaturalcosmetics,driedgrains
ofbeepollenmicronizedandaddedtocosmeticsarealsoused.
Beeswaxisusedincosmeticsafterhoneyhasbeenremovedfromhoneycombs,waxhasbeen
melted,andimpuritieshavebeenseparated.Todothis,varioustypesofwaxextractorsareused:
solar,electricorsteamones.Yellowwax(Ceraflava)orwhitewax(Ceraalba)isusedtoproduce
cosmetics[34].
AccordingtoINCI,beevenomorapitoxinaredefinedasbeevenompowder.Itisyellowlight
powderobtainedbycollectingalargeamountofbeevenombyelectricstunningwithusingabee
venomcollectorwithoutharmingthehoneybee.Thenbeevenomhastobepurifiedunderstrict
laboratoryconditions.Innextsteppurifiedbeevenomisdilutedinwater,centrifuged,lyophilized
andrefrigeratedforuseascosmeticingredient[44].Itisusedasacosmeticingredientswhich
possessesantiaging,antiinflammatoryandantibacterial,antifungalandantiviraleffects.Beevenom
isusedtoproduceantiphotoagingandantiacneproducts[8,44].Beevenomisusedintreatment
psoriasis,atopicdermatitisandalopecia[39].
4.TheEffectofBeeProductsontheSkin
4.1.Honey
Honeyisusedinmedicineincludingduetoitsantimicrobialeffect,whichresultsfromthe
followingfactors:hydrogenperoxide,highosmoticpressure,highacidity,thepresenceofphenolic
acids,flavonoidsandlysozyme[45].Honeyinhibitsthegrowthofbacteriaandfungibyreducing
theirdevelopmentontheskinsurface.Honeyisparticularlysuitableasadressingforwoundsand
burns,andhasalsobeenincludedintreatmentsagainstpityriasis,tinea,seborrhea,dandruff,diaper
dermatitis,psoriasis,hemorrhoids,andanalfissure[40].Pinocembrinandlysozymeareresponsible
forantifungalproperties.Lysozymeinhibitsgrowthofyeastlikefungi[46].Theeffectofhoneyon
healingpostsurgicalwoundswasdocumented[1].Among52patientsincisionsonskinwerecovered
withhoneydressing.Theaestheticoutcomeafterthirdandsixmonthswasrated.Thewidthofthe
scarswassmallerincomparetoconventionaldressing.After5dayapplicationofhoneydressing,an
analgesiceffectwasobtainedandwoundhealingwasacceleratedinwomenafterplasticsurgeries.
HoneyinducedextracellularCa2+entryresultsinwoundhealing.ItissimilartoroleplaysbyCa2+
signalingintissueregeneration[47].Moreoverhoneyregulatestheprocessofepithelial
mesenchymaltransition(EMT)andithasapositiveimpactonwoundhealing.TheeffectonEMT
dependsonthefloralandoriginofthehoney[48].Honeyistheapitherapeuticagentintopical
woundstreatmentduetokillingbacteria,abilitytobacterialbiofilmpenetration,lowingwoundspH,
Reducingpainandinflammation,promotingfibroblastmigrationandkeratinocyteclosure,
promotingcollagendepositionsohoneyhasapotentialroleintheareaoftissueengineeringand
regeneration.Honeyshouldbeconsideredtoincorporateittothebiomaterialtissuetemplatesfor
tissueregeneration.Honeywasusedinelectrospuntemplates,cryogelsorhydrogels[49].Themain
problemofusehoneyintissueengineeringare:cytotoxicityofhighconcentrationsofhoney,thelack
ofprolongedreleaseratesofthehoneyovertime.Sofutureresearchshouldfocusontheseaspects.
Amongdifferenttypesofhoney,astrongantibacterialeffectwasobservedinmanukahoneywhich
containslargeramountofmethylglyoxalthanEuropeanhoneys[50].Theantibioticactivityof
manukahoneyisestimatedbyUniqueManukaFactor(UMF)andmethylglyoxal(MGO)markers
Molecules2020,25,5565of17
[46].Duetoanincreasedcontentofglucoseoxidase,ahigherlevelofhydrogenperoxidethanin
Europeanhoneyscanbeobserved[51].Hydrogenperoxideisresponsibleforproducefreeradicals,
whichcauseoxidativedamagetobacterialcellwalls.TheantimicrobialeffectofhoneyfromNew
Zealandisalsoevidentinundilutedhoneysanditisnotabolishedbycatalases,whichdifferentiates
manukahoneyfromothertypesofhoney.Thistypeofhoneyisusedinthetreatmentofvarious
wounds,includingburns.TheinhibitionvalueagainstStaphylococcusaureusFDA209Pofmanuka
honeyindilutionsfrom1:2to1:128isdeterminedintherangeof2.0–4.5[50].Manukahoneyisused
inmedicinetohealburns,ulcersandwoundsdifficulttoheal,andbringssatisfactoryresults.Manuka
honeyalsosoothesguminflammation,andinhibitstheformationofdentalplaque,fightsthrush,and
preventsperiodontitis[52].AnothervarietyofhoneywithantibacterialactivityisRevamilfromThe
Netherlands.TheantibioticfactorinRevamilisthepeptidedefensin1[46].Beedefensin1
permeabilizesbacteriaandinhibitstheirRNA,DNAandproteinsynthesis[49].Howeverinother
varietiesofhoneyalsothephenoliccompoundsareresponsibleforantibacterialeffect.
Honeyisabeeproductwithahighnutritionalvalueandregenerativepropertiesthatiswhyit
isusedinskincareproducts.Ahighcontentofcarbohydrates,thepresenceoffruitacidsandtrace
elementsareresponsibleforitsnutritionalandregenerativeeffects.Thankstoosmosis,
microcirculationinthedermaltissueisstimulated,whichresultsinitsbetternutritionand
oxygenation.Inthisway,metabolicprocessesarealsostimulated,whichleadstoeliminatingharmful
metabolites,andincreasingregenerativeprocesses.Additionally,honeyhashygroscopicproperties,
absorbingmetabolites,andcausingdetoxificationofthedermaltissue.Thisresultsinanincreasein
theskintension,improvementofitselasticity,revitalizingitscolor,andsmoothingoutwrinkles[52].
Fruitacids,ashoneycomponents,provideanexfoliatingeffectfordeadskincells.Honeycanbeused
aspeelingagentinasugaredform[53].Asaresult,manyvaluablenutritionalcomponents,including
vitamins,candiffusethroughtheskinmoreeasily.Xerosisisrelievedbyfattyacidsandmineralsalts
inhoney.Honeysoothesskinirritations,itisagoodcosmeticforchappedlips,rough,crackedhands,
andfrostbites.Honeyisusedinbalmsandbathproductsbecauseofitstoning,relaxing,conditioning
effectsrelatedtothehighcontentofsimplesugars,thepresenceofessentialoils,andbioelements
[53].Duetothepresenceofflavonoids,honeycanalsoplayanimportantroleinsunprotectionby
preventingskinirritation[40].
4.2.Propolis
Propolisiswidelyusedinmedicine.Thankstoitsantisepticpropertiesitisusedindermatology
totreatstaphylococcal,streptococcalandfungalinfections.Purulentskininfections,hidradenitis,
intertrigo,cheilosis,andthrush,amongotherthings,aretreatedwithpropolis.AsreportedthePropol
T,whichisapropolispreparation,ishighlyeffectiveintreatmentofskinburns[54].Thereare
comparabletherapeuticeffectswhenpropolisandsulfathiazoleareused,however,beeglueissafer,
andhasfeweradverseeffects.Propolisisnotonlyantimicrobialandantiinflammatorybutalsoit
increasescicatrizationandreducespain.Chrysin,whichisaflavonoid,providesananalgesiceffect.
Propolisusedtotreatburnwoundsinpigsincreasedfibrolastproliferation,activationandgrowth
capacity.Propolisstimulatesglycosaminoglycanaccumulationwhatisneededforgranulation,tissue
growthandwoundclosure.Propolisasapitherapeuticagentismoreeffectivelythansilver
sulfadiazine.AccumulationofcollagentypeIinmatrixofaninjurystimulatestherepairprocess
becausecollagentypeIisindispensableforthekeratinocytemigrationandreepithelization.
Moreover,propolisincreasedaccumulationofcollagentypeIIIwhataccelerateshealthyprocess.The
usageofpropolisointmenttotreatburnsasatopicalapitherapeuticproductcouldcontributeto
reepithelization[3].Topicallyappliedpropolisdecreasedpersistentinflammatoryindiabetic
woundsbynormalizingneutrophilandneutrophilelastase.Caffeicacidisresponsibleforanti
inflammatoryeffectofpropolis[55].Genisteinfrompropolisacceleratedwoundhealingand
stimulatedwoundangiogenesisinmicewithdiabetestype1[56].Furthermorepropolismaybe
effectiveinhealingindifferentanimalmodelsincludinganimalswithburnsanddiabeticwounds
[3,55,56].MoreoverpropolisishighlyeffectiveinthetreatmentofAcnevulgaris.Researchers
confirmedthelimitationofoccurrenceofCutibacteriumacnes,i.e.,abacteriumwhichplaysakeyrole
Molecules2020,25,5566of17
inacnevulgarispathogenesis,afterethanolextractofpropoliswasappliedtotheskin[57].The
ethanolextractofpropolisinhibitsalsoStaphylococcusepidermidis.Propolisisusedtomanufacture
cosmeticsfortheskinwithacne,andtoproducedrugsagainstbacterialandfungalinfections[58].
Propolisintheconcentrationof5–20%hasregenerative,repaireffectsandprotectsagainstexternal
factors.Itcanbeusedtoproduceantibedsorespreparations,sinceitfirmsthedermaltissueand
protectsitagainstpathogenicmicrobes[59].Propolisprotectsalsofromultravioletradiation,sinceit
canabsorbUVlightduetothepresenceofcaffeicacid,coumaricacid,andferulicacid.Propolisisa
goodadditivetosunblockers(creams,lotions,sticks,andlipsticks)duetoitspropertiesofanatural
filter,aswellasantioxidative,antiinflammatoryandregenerativeeffects[60].Otherresearchers
showedthatRomanianpropolishadphotoprotectiveeffectsagainstUVBaftertopicalapplicationto
30Swissmice[61].Propolisisalsousedtoproduceprotectivelipsticks.Itisregenerativeandantiviral
incoldsorescausedbyherpexsimplexvirus.Flavonesandflavonolsfrompropolis,especially
galangin,kaempferol,quercetin,haveahighantiviralactivityagainstherpessimplexvirustype1in
vitro[62].Nolkemperetal.observedthatboth,aqueousandethanolextractsofpropoliswere
stronglyantiviralagainstherpessimplextype2(HSV2)[63].Skincarewithproductsbasedon
propolisishelpfulagainstfungalproblemsoftheskinduetothepresenceofflavonoids(pinocembrin
andpinobanksin),phenolicacids(caffeicacid)andterpenes[59].Pinocembrinisolatedfrompropolis
inhibitsthemycelialgrowthofPenicilliumitalicumbyinterferingenergyhomeostasisandcell
membranedamageofthepathogen[64].Shampooswithbeegluecanbeanaturalalternativein
treatmentofdandruffandpreventionofitsrecurrenceduetoitsantifungalandantiseborrheic
properties.Propolishasalsobeenusedformanufacturingtoothpastes.Beeglueinhibitsthe
formationofdentalplaqueandisantimicrobial,therebyitreducesdentalcariesdevelopment.
Propolisethanolextractsinhibitthegrowthofcariogenicbacteria,whichincludemainly
StaphylococcusmutantandStaphylococcussobrinus.Glucosyltransferasemakesbacteriaproduceglucan
theyfeedon,whichisinsolubleinwater.Propoliseliminatescariogenicbacteria,inhibitstheactivity
ofglucosyltransferase,andreducesadherentabilitiesofbacteria[65].Theconductedstudiesshowed
thattheuseoftoothpastewithpropolisreduceddentalplaqueby34.3%annually,whereasnormal
pastereducedtheplaqueby31.9%.Aftertwoyearuseofthepastewithpropolisafurtherreduction
ofplaqueby12.4%wasobserved,whilenormalpastemanagedtoreduceitonlyby5%.Rinsingthe
mouthwithwaterwith0.5%propoliscontentcomplementstheoralcavitycare.After21days,this
solutionwasabletoreducedentalplaqueby18.1%[66].Propolissmoothesoutwrinklesandhas
antiagingproperties.Ahugeroleisplayedherebyantioxidantssuchasphenoliccompoundsand
flavonoidswhichneutralizeanunfavorableeffectoffreeradicalsontheskin.Beegluelightensand
smoothenstheskin,reducessignsoffatigueandmoisturizesit[59].
4.3.RoyalJelly
Royaljellyhasabroadspectrumofbiologicalactivitieswhichdeterminetheeffectofroyaljelly
ontheskin,namely,antibacterial,antiinflammatory,immunomodulatory,antiallergic,antioxidant,
toning,moisturizing,andantiaging[67].Royaljellyisabeeproductwithstrongantimicrobialactivity
withinskintissue,whichisalreadyevidentin20%concentration.Duetoitsantiinflammatory
activity,royaljellyrelievesperiodontaldiseases,inflammationoftheoralcavity,tongueandthroat.
Antiinflammatoryactivityandwoundhealingresultsfromitsabilitytoinhibittheproductionof
proinflammatorycytokines(TNF‐α,IL6,IL1).Royaljellyhasaprotectiveeffectonbloodvessels
andrelieveshemorrhoids,andvaricoseveinsofthelowerextremities.Itisusedtotreatlichen,ulcers,
burns,bedsores,shingles,inallcaseswheretheregenerationofepidermisisexpected,wound
epithelialization,nutritionaleffect,healingandantimicrobialactivity.Theeffectof5%royaljellyon
ulcersonthediabeticfoothasbeenstudied.Thetreatmentlasted3monthsandinvolveddressing
thewoundwith5%sterileroyaljelly3timesaweek.Amongeighttreatedulcers,sevenwerecured,
andinonecaseanimprovementwasobserved[68].Royaljellypromoteswoundreepithelization.
ThekeratinocytesareresponsiblefortheelevatedproductionofMMP9(matrixmetalloproteinase
9)afterincubationwithawaterextractofroyaljelly.Afterapplyingwaterextractofroyaljelly
increasedkeratinocytemigrationandwoundclosurerates.Thecomponentofroyaljellyresponsible
Molecules2020,25,5567of17
forstimulatingMMP9productionisdefensin1.Moreoverdefensin1promotesreepithelizationand
woundclosure.Similarlyasinhoney,defensin1isresponsibleforcutaneouswoundclosureby
enhancingkeratinocyteandMMP9secretion[69].Royaljellyiseffectiveinthetreatmentofwounds,
andissuccessfullyusedincosmeticsforproblemskincare.Royaljellyisaningredientof
preparationsnormalizingsebumsecretion,forseborrheicskin,acneproneskinwherefrequently
skinlesionsandsmallwoundsoccur[31].Duetostimulatingmetabolismintissues,royaljelly
improvesregenerativeprocessesoftissues.Regenerative,nutritionalandhealingpropertiesareused
inbalms,creams,andlotions.Immunomodulatoryandantiallergenicactivitiesofroyaljellyare
relatedtothepropertiesoffattyacids,isolatedfromit.Both,10HDAand310dihydroxydecanoic
acidmodulateimmuneresponseandlowertheconcentrationofIL2andIL10.Antiinflammatory
andimmunomodulatoryactivitiesofroyaljellywereusedtotreatatopicdermatitis,hypertrophy,
hyperkeratosisandepidermisanddermisinflammation,possiblythroughablendofTNFspecific
lowadjustmentofIFNgammaspecificproductionandhighadjustmentofnitricoxidesynthase
(NOS)expression[70].10hydroxytrans2decenoicacid,whichispresentinroyaljelly,stimulates
fibroblastproductionofcollagenbyinductingtheproductionoftransforminggrowthfactor.Asa
result,royaljellyaffectstheproductionofcollagen,whichisanimportantfactorthatsupportsthe
skin[28].Royaljellyishighlymoisturizing,andaffectshydrationofthestratumcorneumbyretaining
waterinit.Inconsequence,theskinbecomemoreelasticandbettermoisturized[42].
4.4.BeePollen
Beepollen,anotherbeeproduct,canalsoaffecttheskin.Beepollenisapotentantifungal,
antimicrobial,antiviral,antiinflammatory,immunostimulatingagent,anditalsofacilitatesthe
granulationprocessofburnhealing[71].PollenethanolextractisantimicrobialagainstStaphylococcus
aureus,Escherichiacoli,Klebsiellapneumoniae,Pseudomonasaeruginosa,andhasanantifungalactivity
againstCandidaalbicans.Flavonoidsandphenolicacidsprovideantifungalandantibacterial
propertiesofbeepollen.Antiinflammatoryactivityofbeepollenisduetoinhibitingtheactivityof
enzymesparticipatinginthedevelopmentofinflammation,i.e.,cyclooxygenaseIIandlipoxygenase.
Phenolicacids,fattyacidsandphytosterolsareresponsibleforantiinflammatorycharacteristics.
Additionally,kaempferolinhibitshyaluronidaseandelastase,whichsuppressesinflammatory
response.Besides,topicalapplicationofointmentwithpollenextracttotreatburnshasbeenstudied,
sincebeepollencanregeneratedamagedtissues[2].
Beepollenisanactiveingredientincosmetics,usuallyintheconcentrationof0.5–5%[43].Its
significanteffectontheskintissueisduetoahighcontentofflavonoids.Theirpresenceallowsbee
pollentostrengthenandsealcapillaries,whichisalsoincreasedbyhighvitaminCcontent,andthat
iswhybeepollenisusedincreamsforcouperoseskin.Beepollenaffectscellmetabolism,boosts
regenerationandstimulatesmitoticdivision.Beepollenisusedtoproduceshampoosand
conditioners.Itssebobalancingactivity,whichinvolvesreducingsebumsecretion,isusedin
preparationsforoilyhair. Beepollennormalizestheactivityofsebaceousglandsduetopresenceof
zinc,methionineandphospholipids.Moreover,sulphurcontainingaminoacids,mainlycysteine,
presentinbeepollenstrengthenhairshaft.Beepollenisalsoaddedtoantidandruffshampoos,since
itlimitsfungalgrowthandstopsitchingofthescalp,butitstillhasmoisturizing,conditioningand
regeneratingproperties.Otherresearchersinformthatagoodsolutionwouldbetomixethylesters
ofessentialunsaturatedfattyacidsfromflaxseedswithbeepollen.Essentialfattyacids(EFA)would
playtheroleoflipidfractionsolvent.Preparationswithomega3andomega6acidsenrichedwith
diversepropertiesofbeepollencouldhelpinthecareofatopicskin,sensitiveskin,andtheskinmore
vulnerabletoscarring[43].
4.5.Beeswax
Whencomparedtootherbeeproducts,beeswaxhasthesmallestrangeofbiologicalactivities.
Kędzia[34]wrotethatbeeswaxwasaddedtoointments,linimentsandcreamsusedintreatmentof
variousdermatoses,e.g.,boils,wounds,atopicdermatitis,psoriasis,diaperdermatitiscausedby
Candidaalbicans.Beeswaxismainlyusedasanemulsifyingagent.Incosmetics,beeswaxisusedasa
Molecules2020,25,5568of17
stiffener,asubstanceprovidingelasticity,plasticityandincreasingskinadhesiveness.Beeswaxisthe
baseforlipsticks,sticksandcreams[72].Beeswaxhaslubricating,softeningactivitiesandreduces
transepidermalwaterlossfromskin.Sterols,whicharealsocomponentsofintercellularspace,
providethesecharacteristicsofbeeswax.Squalene,10hydroxytrans2decenoicacidandflavonoids
(chrysin)provideantisepticpropertiestothisproduct,andprotecttheskinagainstpathogenic
microorganisms.Beeswaxconstitutesaprotectivebarrieragainstmanyexternalfactorsbyforminga
filmontheskinsurface.β‐carotenepresentinbeeswaxisavaluablesourceofvitaminA,intowhich
itisconverted.VitaminAdelayscollagendegradation,stimulatesmitoticdivisionintheepidermis,
thusleadstosoonerregenerationoftheskinafterdamage[34,36].
Themaineffectsofflavonoidsandphenolicacidspresentinabovebeeproductsontheskinare
presentedinTable1.
Table1.Maineffectsofselectedflavonoidsandphenolicacidsonskin.
GroupRepresentativeStructureEffect
Flavones
Chrysin
antiinflammatory[73],
antibacterial&antiviral[74],
antioxidant[22]
Apigenin
antiviral&antifungal[74],
antiallergic[75],
antioxidant[22]
Flavonols
Galangin
antiviral[62],
antifungal[76],
antioxidant[22]
Kaempferol
antiinflammatory[77],
antifungal&antiviral[74],
antioxidant[22],
UVphotoprotective[78]
Quercetin
antiallergic[2],
antiviral&antifungal[74],
antibacterial[12],
antioxidant[79],
UVphotoprotective[78],
antiinflammatory[77]
Flavanones
Pinocembrin
antifungal[76],
antioxidant[22]
Naringenin
UVphotoprotective[80],
antioxidant[79],
antiinflammatory[77],
antiviral[74]
Phenolic
acidspCoumaric
antiviral[20],
antibacterial[46]
O
OH
OH O
O
OH
OH O
OH
O
OH
OH O
OH
O
OH
OH O
OH
OH
O
OH
OH O
OH
OH
OH
O
OH
OH O
O
OH
OH O
OH
OH
O
OH
Molecules2020,25,5569of17
Table1.Cont.
Caffeic
antiinflammatory[55],
antiviral[20],
antibacterial[46],
antifungal[59]
Ferulic
antibacterial[46],
photoprotective[60]
4.6.BeeVenom
Beevenomhasbeenusedinmedicineintreatmentbutalsoasacosmeticingredient.Beevenom
hasawidespectrumofbiologicalactivity.Itexhibitantibacterialandantiinflammatoryeffectssoit
canbeusedasaingredientofantiacneproducts.Beevenomshowsinhibitoryeffectson
Cutibacteriumacnes.Cutibacteriumacnesisthemainfactorinducingtheinflammationinacne.Anet
al.[81]showedthattopicalapplicationbeevenomonmiceskin,whichpreviousobtained
intradermallyinjectedCutibacteriumacnesintoears,limitednumberofinflammatorycellsandalso
reducedleveloftumornecrosisfactor(TNF)‐αandinterleukinIL1β.Moreover,beevenominhibited
Tolllikereceptor(TLR2)andCD14expressionintissuewhichhasbeeninjectedC.acnes.Theseresults
indicatethatbeevenomcanbeusedasantiacneagent.Anotherresearchers[82]alsoshowedpositive
effectsofcosmeticscontainingbeevenomonacnevulgaris.Purifiedbeevenomreducednumberof
C.acnesatconcentrationof0.5mg.Beevenompossessesbactericidalandbacteriostaticeffectsthanks
tomelittin[38].IthasasignificantantibacterialeffectagainstStaphylococcusaureus,Staphylococcus
epidermidisandStaphylococcuspyrogenes[39,83].Melittinisatoxicpeptidethatcausesdestructionof
thebacterialcellwall[38].Beevenomcanbeusedinfungiandviralskininfections.Theantifungal
effectofbeevenomagainstTrichophytonmentagrophytes,Trichophytonrubrum,Candidaalbicansand
Malasseziafurfurwasproved[84–86].Antiviraleffectofbeevenomonherpessimplexvirushasbeen
studied.Beevenomsuppressedthereplicationthisvirus[87].Moreoverbeevenomisapotential
inhibitorof5αreductase,whichisresponsibleforconversetestosteroneintodihydrotestosterone
andplaysimportantroleashairgrowthpromoter,whatwasconfirmedinstudyonalopecia.Bee
venomindifferentconcentrations0.001%,0.005%and0.01%wasappliedincompare2%minoxidil.
Researchersshowedthatbeevenompromotedhairgrowthandinhibitedtransitionfromtheanagen
tocatagenphase.AdditionallybeevenominhibitedtheexpressionofSRD5A2whichencodesa5‐α‐
reductase[88].Beevenomcanplayroleasanewtherapyinlocalizedplaquepsoriasis.Intradermal
beevenomandintradermalbeevenomcombinedwithoralpropolisconstituteeffectivetreatmentof
localizedplaquepsoriasis.BeevenomreduceslevelofIL1β,TNF‐α,andIL6.Beevenomcontains
melittin,whichblockstheexpressionofinflammatorygenes.Additionallybeevenominhibitsthe
COX2expression,sodecreaseproductionofprostaglandinswhichtakepartininflammatoryprocess
[89].Beevenomcompoundspossessvarious,sometimeopposingimmunerelatedeffects.Some
componentsofbeevenomlikeapamin,histamine,mastcelldegranulating(MCD)peptideand
phospholipaseA2(PLA2)increaseinflammatoryresponse,whilepolypeptideadolapininhibits
prostaglandinssynthesisandinhibittheactivityofbeevenomPLA2andhumanlipoxygenase[90].
Antiinflammatoryeffectofbeevenomisusedalsointreatmentatopicdermatitis.Patientswho
appliedemollientwithbeevenomhadlowereczemaarea,severityindexandvisualanaloguescale
valuethanpatientswhoappliedemollientwithoutbeevenom[84].Thebiologicalactivitiesofbee
venomhavebeenusedinwoundshealing.Themechanismofwoundhealingisassociatedwith
expressionsofTGF‐β1,fibronectin,vascularendothelialgrowthfactor(VEGF)andcollagenI.The
research,whichwasconductedinmiceshoweddecreasingofwoundsizeandincreasingepithelial
proliferation.Topicaluseofbeevenomiseffectiveespeciallyinreducingsizeofwoundsinanimal
model[83].Thebeevenomisusinginwounddressingcombinedwithpolyvinylalcoholand
OH
O
OH
OH
OH
O
OH
OCH
3
Molecules2020,25,55610of17
chitosan.4%beevenominwounddressingindiabeticratsacceleratedhealingandlimited
inflammatoryprocess[91].Anotherstudyshowedthat6%beevenomwithchitosansupported
woundhealing[92].Researchersindicatedthatbeevenomstimulatedhumanepidermalkeratinocyte
proliferationandmigration.Beevenomjoinedwithhydrogelincreasedcollagenformation.Bee
venomsupportswoundhealingduetoitsantiinflammatory,antimicrobialandalsoantioxidant
activity.EffectiveactionofbeevenomisveryimportantinhumanmelanomaA2058cells.Tuetal.
exhibitedthatbeevenomleadstoapoptosiscelldeathbyinductionhydroxylradicals[93].Recently
beevenomalsohasbeenusedasantiwrinkleagent.Asacosmeticingredientbeevenomserumata
concentrationof0.006%wasappliedatamount4mLtwiceadayfor12weeksamongtwentytwo
womenfromSouthKorea.Itcauseddecreasingtotalwrinklearea,totalwrinklecountandwrinkle
depth.Moreoverbeevenompossessesantimelanogenicactivitybyinhibitingtyrosinaserelated
proteins[94].ThestudyconductedbyHanetal.[44]reportedthatbeevenomexhibits
photoprotectiveactivitybyreductingoftheproteinlevelsofmatrixmetalloproteinases.Beevenom
effectivelyinhibitsphotoagingprocessessoitcanbeusedforphotodamagedskin.Gelcontaining
0.06%beevenomdidnotleadtophotosensitivedermatitiswhathasbeenconfirmedonanimalmodel
[8,44].
5.AllergicAdverseEffectsofBeeProducts
Theuseofbeeproductsforcosmeticaswellasmedicineproductioncaninvolvetheoccurrenceof
allergicreactions.Anallergytohoneyisseldom,andthemostfrequentallergenfromhoneythatcauses
hypersensitivityreactionsisbeepollen.Additionally,beeproteininhoneycancauseanallergy.Honey
usedtotreatdermatosesundergoesthoroughfiltrationtoeliminateparticlesofbeepollen,whichare
themaincauseofhoneyallergicreactions.HoneyallergyisveryrarebutsometimescausesIgE
mediatedhypersensitivityreaction[95].In2010Basistaconductedstudiesonbeekeepers.Noneofthem
washypersensitivetohoney[96].Morethan26allergenicsubstancesweredeterminedinpropolis
composition.Mostfrequently,anallergicreactioniscausedbyestersofcaffeicacidandcinnamicacid
derivedfrompoplarbuds.Inhypersensitivepeople,theycauseacontactallergicreaction.Duetothe
presenceoftheseestersinothermaterials,crossallergicreactioncanoccur.Themostpotentalergens
are:LB1,i.e.,thecompoundconsistingof3methyl2butylcaffeate(54.2%),3methyl3butylcaffeate
(28.3%),2methyl2butylcaffeate(4.3%),caffeicacid(1.3%),benzylcaffeate(1.0%),caffeicacid
phenethylester(CAPE,7.9%)andbenzylsalicylate.Anallergytopropolisisrare,andanallergic
responsewasmorefrequentlyreportedaftertopicalapplicationthananoralone.Intheyears1989–
2006,theWorldHealthOrganizationregisteredonly26notificationsaboutsideeffectsafterthecontact
withbeeglue,ofwhichjustsixwereconsideredcertain,andtheremainingoneswerenotfullycredible.
Inhealthyindividuals,anallergytopropolisisrarelyobserved(0.64–1.3%),however,itoccursmore
frequentlyinpeopletreatedforallergies(1.2–6.7%).Thishypersensitivityismanifestedbyatopic
eczemaaftertheapplicationofethanolextractofpropolis[97].Moreover,topicalapplicationofroyal
jellyintheformofointmentscancauseskinrashesandeczemas[67].Allergicandirritationreactionof
beevenomhavebeenassociatedwithpresencecomponentslikes:phospholipaseA2,melittin,
hyaluronidase.PhospholipaseA2isamajorallergenwhichisresponsibleforinducingimmuno
globulinE(IgE)[98].MelittincausescelllysisandfusioninadditiontoactivationofphospholipaseA2.
Hyaluronidaseisanextallergeninvenom,whichisresponsibleforchangesincellmembranes.It
causedspreadofvenomtoxinthroughthegapsbetweencells.However,beevenomcanbetoxicwhen
largeamountofvenomisinoculatedintobody[98].However,Hanetal.indicatesthatlongterm
topicallytreatmentwithbeevenomissafewhatconfimedtheirstudy[94].
6.Conclusions
Beeproductsconstituteanimportantcomponentofmedicinesandcosmetics.Honeyis
regenerativeandantimicrobialduetoitshighosmolarity,thepresenceofhydrogenperoxideand
lysozyme.Manukahoneythankstothepresenceofmethylglyoxalisapotentantisepticagent.Propolis
isabeeproductrichinphenoliccompounds,whichdetermineantimicrobial,UVprotective,analgesic,
antioxidativeandregenerativeactivities.Royaljellyischaracterizedbythepresenceofroyalisinand
Molecules2020,25,55611of17
jelleinespeptides.Italsocontains10hydroxytrans2decenoicacidwhichimprovestheproductionof
collagenandisantiseptic.Beepollenisrichinunsaturatedfattyacids,vitamins,flavonoidsandhydroxy
acids.Beeswaxplaysthemostimportantroleasemulsifierofthecosmeticforms.Moreover,beevenom
isanattractiveandeffectivenaturaltoxinrichinpeptides.Itplaysanimportantroleintreatmentand
careskinespeciallyinphotodamage,acne,atopicdermatitis,alopeciaorpsoriasis.Beevenomexhibits
antiinflammatory,antimicrobial,antifungalandantiviralaction.Eachofthebeeproductsis
characterizedbythecontentofcertainactivesubstances,whichdifferentiatesonebeeproductfrom
another,andcausesthateachofthemisworthusingforadifferentskinproblem.Theeffectofbee
productsontheskinhasbeenprovedbynumerousstudies,whoseresultsaresatisfactory,andtheuse
oftheseproductinwoundhealinghighlightstheircurativevalue.Theadvantageofmedicinesand
cosmeticsbasedonbeeproductsistheireffectivenesswithminimalsideeffects. Table2summarizes
skindiseaseswherethetherapeuticapplicationofbeeproductshasbeenstudied.
Table2.Thesummaryoftheskindiseaseswherethetherapeuticapplicationofbeeproductshasbeen
studied.
Bee
ProductComponentsEffectDiseaseReference
Honey
pinocembrin,lysozymeantifungaltinea[13,46,64]
methylglyoxal,defensin1
peptide,lysozyme,glucose
oxidase,phenolicacids
antibacterialwounds,burns,ulcers[13,16,45,46,50]
fruitsacids,sugarsexfoliatingwrinkles[13]
quercetin,naryngenin,
kaempferol,chrysinantiinflammatorywounds,guminflammation[49,52]
carbohydrates,fruitacids,
traceelementsregenerativewounds[40,49,52,53]
Propolis
chrysinanalgesicwounds[3]
caffeicacid,quercetinantiinflammatorywounds[19,55]
pinocembrin,galangin,
caffeicacidantibacterialacne,wounds [19,57,65,66]
pinocembrin,pinobanksin,
quercetin,kaempherol,
caffeicacid,pcoumaricacid,
terpenes,
antifungaltinea,fungalinfections[19,59]
galangin,kaempferol,
quercetinantiviralinfectionofHerpessimplex
virus[62,63]
caffeicacid,pcoumaricacid,
ferulicacid,quercetin,
kaempferol
photoprotectivephotoaging[60]
phenolicacids,flavonoidsantiagingwrinkles[59]
genisteinstimulates
angiogenesisdiabeticwound[56]
Royaljelly
defensin1peptid,ferulicacidantibacterialwounds,diabeticfoot
ulcers,acne[32,67,68]
10hydroxydecanoicacid,3
10dihydroxydecanoicacid,
amino,gammaglobulin
antiinflammatoryatopicdermatitis,wounds,
hypertrophy,hyperkeratosis[67]
10hydroxytrans2decenoic
acid,10hydroxydecanoicacidantiagingwrinkles[67]
10hydroxydecanoicacid,3
10dihydroxydecanoicacid
immunomodulatory
andantiallergenic
autoimmuneand
inflammatorydiseases[70]
Beepollen
pinocembrin,apigenin,
quercetin,kaempferol,ferulic
acid,pcoumaricacid
antifungaltinea[2,24,43]
kaempferol,phenolicacidsantimicrobialburns[2,6,24,43]
phenolicacids,fattyacids,
phytosterols,kaempferol,
quercetin
antiinflammatoryatopicdermatitis,burns[2,43]
methionine,zinc,
phospholipidssebobalancingacne[43]
Molecules2020,25,55612of17
Table2.Cont.
Beeswax
squalene,10hydroxytrans2
decenoicacid,chrysinantibacterialwounds,atopicdermatitis,
psoriasis[34,36]
sterolsreducetransepidermal
waterlossatopicdermatitis[34]
Beevenom
melittinantimicrobialwounds,acne[39,81–83,92]
melittin,apaminantifungaltinea[84–86]
melittinantiviralherpessimplexinfections[84–87]
notreportedphotoprotective,
antimelanogenichiperpigmentation[44,94]
melittin,adolapinantiinflammatoryplaquepsoriasis,wounds,
atopicdermatitis[83,84,89,91,92]
phospholipaseA2pigmentationeffectvitiligo[39]
notreportedpromotehairgrowthalopecia[88]
notreportedantiwrinklewrinkles[44,94]
AuthorContributions:A.KG.designedthereview;coordinatedandparticipatedinthewritingofallsections
andwroteAbstract,Sections13,Section4.1,Section4.6andSection6andcollaboratedinthecreationofTable
1;M.G.wroteSection4.3andcreatedTables1and2andcollaboratedinthewritingofSection4.2;A.RzS.wrote
Section4.2andcollaboratedinthewritingofSection5;R.B.wroteSection4.4andSection4.5;J.S.wrotethe
Section5.Allauthorswereinvolvedintheeditingprocess.Allauthorshavereadandagreedtothepublished
versionofthemanuscript.
Funding:ThisworkwasfundedbyMEDICALUNIVERSITYOFSILESIA,KATOWICE,POLANDgrantnumber
KNW1163/N/9/O.
Acknowledgments:TheauthorsthankstoMEDICALUNIVERSITYOFSILESIA,KATOWICE,POLANDand
SILESIANACADEMYOFMEDICALSCIENCESINKATOWICEfortheirfinancialsupport.
ConflictsofInterest:Theauthorsdeclarenoconflictofinterest.
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... The highlighted modulation of the specific biochemical cascade supports the in vivo evidence of the functional role of HCC coupled to SH in commercial preparations [13]. It must be considered that conventional treatments like biologics (e.g., TNF-α inhibitors) increase the risk of systemic immunosuppression, whilst the proposed topical treatment based on HCC + SH exhibit none/minimal side effects [41,42]. This makes the formulation a promising option for long-term management of psoriasis, especially in patients seeking alternatives to systemic treatments. ...
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Salvia haenkei (SH-Haenkenium®), a native plant of Bolivia, is known as strong inhibitor of senescence and recently exploited in wound healing and for its potential anti-inflammatory properties. Hyaluronan at high and low molecular weight (HCC), explored in diverse cell models, and recently used in clinical practice, showed beneficial effects in dermo aesthetic and regenerative injective treatments. In this research work a novel formulation based on HCC coupled SH was tested for its potentiality in counteracting dermal injury. In vitro wound healing has been used to demonstrate HCC + SH capacity to improve keratinocytes migration respects the sole HCC, supported also by positive modulation of remodeling and integrity biomarkers. In addition, an in vitro dehydration test showed its ability to defend the skin from dryness. Moreover, an in vitro inflammation model (with lipopolysaccharides derived from E. coli) was used to assess molecular fingerprint of the pathological model and compare the cell response after treatments. Inflammatory biomarkers (e.g., KRT6, TLR-4 and NF-κB) and specific cytokines (e.g., IL-6, IL-22, IL-23) proved the effect of HCC + SH, in reducing inflammatory mediators. A more complex model, 3D-FT skin, was used to better resemble an in vivo condition, and confirmed the efficacy of novel formulations to counteract inflammation. All results trigger the interest in the novel formulation based on SH extract and hyaluronan complexes for its potential efficacy as natural anti-inflammatory agent for damaged skin, for its healing and regenerative properties.
... Honeybee products are among the most frequently used natural ingredients in dermatology and skincare [2]. Furthermore, the positive clinical outcomes from topical application of honey have led to the development of 'medical-grade honey' . ...
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Background Honey has been successfully used in wound care and cosmetics because of its effective biological properties, including antibacterial, antioxidant, and anti-inflammatory activities. Polyphenols, particularly phenolic acids, are key honey components responsible for these beneficial effects. In recent years, there has been a growing demand for natural, ecologically friendly, and biodegradable products in the modern cosmetics and wound care market. This study aimed to identify and quantify phenolic acids in four Polish honey samples of different botanical origins (heather, buckwheat, linden and rapeseed) and to assess for the first time the permeation of the identified phenolic acids through the skin and their accumulation after the application of pure honey samples, as well as honey-based hydrogel and emulsion formulations. Methods The honey samples’ antioxidant activity and total phenolic content were determined using the DPPH and ABTS assays and the Folin–Ciocalteu method, respectively. Phenolic acids and volatile compounds were identified and quantified in honey samples using the HPLC-UV and GC-MS method, respectively. The biocompatibility of the honey samples was evaluated using a murine fibroblast cell line (L929). A Franz-type vertical diffusion cell with porcine skin was used to assess phenolic acid’s permeation and skin accumulation from different honey-based pharmaceutical formulations. The biodegradability of the prepared formulations was also characterised. Results Gallic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid, coumaric acid, and 3-hydroxybenzoic acid were identified and quantified in the honey samples. Heather honey exhibited significantly higher antioxidant activity and total polyphenol content than the other honey samples. Heather, linden and buckwheat honey samples significantly decreased cell viability at concentrations of 5% and 2.5%, while rapeseed honey sample markedly reduced fibroblast viability only at 5%. Among the tested formulations - pure honey, hydrogel, and emulsion - higher skin permeation and accumulation rates of phenolic acids were observed with the prepared honey-based hydrogels than with the pure honeys and emulsions. Additionally, the prepared formulations were classified as partially biodegradable. Conclusions The obtained results confirmed the effectiveness of two pharmaceutical formulations in the form of a hydrogel or emulsion containing honey after applied topically. The inclusion of honey in the vehicle, in particular hydrogel increased the penetration of phenolic acids through the skin.
... Through intrinsic resistance, the bacterium naturally resists the effects of certain antibiotics due to its innate structural and functional characteristics (the structure Honey is a natural medicinal substance that contains the active ingredients of the nectar source plant and the special enzymes and hormones of bees. The bactericidal hydrogen peroxide produced through the dilution of honey, the plant-derived polyphenols that increase the permeability of the bacterial cell membrane, the peptides synthesized by bees (e.g., defensin-1 peptide), the slightly acidic pH (bacteriostatic effect), and the high sugar content (osmotic stress) all contribute to honey's antibacterial activity [20][21][22][23][24]. The strong antibacterial effect of linden honey (Lh) and chestnut honey (Ch) has been confirmed by several research groups, suggesting that their use as adjunctive therapy may also be effective in the case of otitis media [25][26][27][28][29][30]. ...
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The current investigation was carried out to evaluate the state of nanotechnology and microbiology along with detection of heavy metals present in bee honey, all of these are active areas of study at the moment. Tremendous abilities of honey i.e. being an antioxidant to antibacterial in nature all of these properties fetching the attraction of human kind towards itself. For decades, nanotechnology has been a source of worry, and the field has only gotten more intriguing as time has progressed. Nanoparticles are "tiny champions" of the technical world because they enable previously inconceivable procedures. Research into nanoscience and nanotechnology has advanced throughout the years, with applications across many different types of objects. Nanotechnology has been coined to describe the application of nanoscience and nanotechnology to the subject of biology; this is necessary due to the inherent nanoscale nature of cellular components. MNPs have extreme features not often seen in larger particles due to their high surface-to-volume ratio and the enormous number of atoms and molecules at their borders. Their method of action is affected by their size and shape when used in in-vivo research. Subtle alterations to their distinguishing feature have dramatic effects in the wild. These nanoparticles can be mono-metallic, bi-metallic, or multi-metallic, depending on how many metals are used in their construction. In this research, mineral evaluation of honey together withproduction and characterisation of mono-metallic silver, iron, nickel and zinc nanoparticles were the primary areas of investigation. There are several benefits to using mono nanoparticles rather than other ones. The usefulness of monometallic nanoparticles (MMNPs) was improved by their unique mixing patterns and geometrical architecture. They perform outstandingly in terms of stability, selectivity, and catalytic activity. In this work, mineral analysis and metallic nanoparticle synthesis were performed in an appropriate laboratory setting, therefore the authors opted for the bottom-up approach, which involves producing nanostructures by constructing them from the ground up. In the bottom-up method, atoms and molecules are carefully separated before being synthesised onto 0-200 nm nanoparticles. When discussing the relative merits of the various approaches used for synthesising metallic nanoparticles biological synthesis was always kept at the priority. In comparison to the high capital cost, high energy consumption, or the use of toxic solvents required for physical or chemical synthesis of metallic nanoparticles was way more than that of biological synthesis. Here the bee honey used as derivative for synthesis of nanoparticles was more less toxic, rapid, environmental friendly, cost-effective and can be carried out in small spaces under normal lab conditions. Although nanoparticles have many applications in clinical research, their work as antimicrobials is particularly impressive. Many pathogenic microorganisms have developed resistance to current antibiotic treatments. The creation of biofilm surrounding bacterial colonies, which renders them multi-drug resistant to available antibiotics, appears to be the primary source of their resistance. Nanoparticles become relevant in this context. Their involvement in fighting infections has been demonstrated via research. They do this by disrupting microbial biofilms. Biofilm formation was inhibited or the bacteria were prevented from establishing themselves. In particular, the ability of metal nanoparticles to inhibit the growth of biofilms produced by pathogens like Escherichia coli MTCC 40 and Bacillus megaterium ATCC® 14581was taken into account throughout the study's design. In this study, bee honey was the main agent for the synthesis of MNPs, because it posses with phenolic and flavonoids compounds in it, which made it a good capping and reducing agent for the synthesis of Ag, FeO, NiO and ZnO NPs. The honey samples were fully flourished with antioxidants who made honey as brilliant option for the synthesis of MNPs numerous physicochemical approaches were used to characterise the synthesised nanoparticles, and the results confirmed that these particles all fall within the nano-range and had a crystalline structure. Some are square or cylindrical, while others are round or octagonal. They are finely doped with barely detectable contaminants and their surface topography suggests minor aggregation during production. Due to the prevalence of harmful bacteria in the area, including those that may build biofilm and acquire tolerance to existing medications, it is more difficult to treat an infection quickly. This research centred on a specific kind of invasive Escherichia coli that develops a biofilm on surfaces like catheters and gastrointestinal lining, making treatment more challenging. E. coli was selected from a large number of bacterial samples recovered from the environment and clinical sources. Pathogenic E. coli was verified in all bacterial samples by scientific and molecular examination. Bacillus megaterium was selected for its spore formation in honey, soil, seawater, sediments, rice paddies, dried food and milk. It was verified with its molecular analysis. The efficacy of the synthesised nanoparticles in opposition to bacterial samples was also shown to be outstanding, making this study profitable for the field of nano-medicine in the creation of nano-based medications against biofilm producing infections, hence aiding in the treatment of the condition in less time than usually necessary. 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Skin is larger than any other organ in humans. Like other organs, various bacterial, viral, and inflammatory diseases, as well as cancer, affect the skin. Skin diseases like acne, atopic dermatitis, and psoriasis often reduce the quality of life seriously. Therefore, effective treatment of skin disorders is important despite them not being life-threatening. Conventional medicines for skin diseases include corticosteroids and antimicrobial drugs, which are effective in treating many inflammatory and infectious skin diseases; however, there are growing concerns about the side effects of these therapies, especially during long-term use in relapsing or intractable diseases. Hence, many researchers are trying to develop alternative treatments, especially from natural sources, to resolve these limitations. Bee venom (BV) is an attractive candidate because many experimental and clinical reports show that BV exhibits anti-inflammatory, anti-apoptotic, anti-fibrotic, antibacterial, antiviral, antifungal, and anticancer effects. Here, we review the therapeutic applications of BV in skin diseases, including acne, alopecia, atopic dermatitis, melanoma, morphea, photoaging, psoriasis, wounds, wrinkles, and vitiligo. Moreover, we explore the therapeutic mechanisms of BV in the treatment of skin diseases and cytotoxic effects of BV on skin disease-causing pathogens, including bacteria, fungi and viruses.
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Introduction Honey has been considered to have therapeutic properties since ancient times and among the factors responsible for such activity are phenolic compounds including phenolic acids and flavonoids from different natural sources. Objective This study investigated the phenolic compounds profile and bioactive properties of different honey types from Romanian flora in order to develop reliable tools for honey floral origin, thus contributing to the honey traceability in the European Union context. Material and methods Thirty‐three honey samples were examined, including unifloral (acacia and rape), polyfloral, honeydew honeys and mixture honeys. Phenolic acids and flavonoids were isolated from the water soluble honey matrix using a solid‐phase extraction (SPE) method and analysed by ultra‐high‐performance liquid chromatography diode array detector electrospray ionisation mass spectrometry (UHPLC‐DAD‐ESI/MS). Honey bioactive properties were measured in honey dissolved in 80% ethanol using UV‐visible spectrophotometric methods. Multivariate statistical tools (principal component analysis and hierarchical clustering analysis) were used for honey classification. Results The results of this study confirm that honey samples had similar, but quantitatively different, phenolic acids and flavonoids profiles and bioactive properties, related with honey floral source. Coloured honeys, such as honeydew honey, show high phenolic composition and bioactive properties and implicitly a high therapeutic potential compared with the other floral honeys. Conclusion Distinctive clusters obtained by principal component analysis enabled us to consider that honeydew and polyfloral honeys could be distinguished from acacia and rape honey with the analytical methods developed. Based on this study, the methods might be promising tools for honey traceability, which needs to be explored on a larger set of samples with different regional floral origins in future studies.
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Since Biblical times, honey has been utilized in “folk medicine”, and in recent decades the positive qualities of honey have been re-discovered and are gaining acceptance. Scientific literature states that honey has been successfully utilized on infections not responding to classic antiseptic and antibiotic therapy, because of its intrinsic H2O2 production. In our study, we demonstrated the involvement of H2O2 as a main mediator of honey regenerative effects on an immortalized human keratinocyte cell line. We observed that this extracellularly released H2O2 could pass across the plasma membrane through a specific aquaporin (i.e., AQP3). Once in the cytoplasm H2O2, in turn, induces the entry of extracellular Ca2+ through Melastatin Transient Receptor Potential 2 (TRPM2) and Orai1 channels. Honey-induced extracellular Ca2+ entry results in wound healing, which is consistent with the role played by Ca2+ signaling in tissue regeneration. This is the first report showing that honey exposure increases intracellular Ca2+ concentration ([Ca2+]i), due to H2O2 production and redox regulation of Ca2+-permeable ion channels, opening up a new horizon for the utilization of the honey as a beneficial tool.
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Bee Bread samples from Romania and India were analysed by microscopy and High Performance Liquid Chromatography with Diode Array Detection (HPLC/DAD) and compared with pollen from the correspondent taxa. The quantification of sugars, fructose/glucose ratio, total phenolics and flavonoids was also carried out. From the results was possible to identify Brassica and Eucalyptus samples that present similar HPLC/DAD profiles with the respective ultraviolet (UV) identification of the main compounds as Kaempferol-3-O-glycosides and Hydrocinnamic acid derivatives. The Fructose/Glucose (F/G) ratio and the total amounts of phenolics and flavonoids was in line with the prevalence of the specie identified. These coincident fingerprints gave the identification of the samples, as was previously proposed for bee pollens. This paper relates for the first time the achievement on the taxon carried out previously only for bee pollens. It was reported for the first time that this phenolic profile remains unchanged in the case of floral pollen (hand collected), bee pollen and bee bread. Despite the biochemical transformation that occurs during the fermentation of bee bread, it seems that these phenolic compounds are not affected and remain unchanged. Also, variables such as soil and climate do not seem to influence these compounds for the kind of samples under study.
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Over the past few decades, there has been a resurgence in the clinical use of honey as a topical wound treatment. A plethora of in vitro and in vivo evidence supports this resurgence, demonstrating that honey debrides wounds, kills bacteria, penetrates biofilm, lowers wound pH, reduces chronic inflammation, and promotes fibroblast infiltration, among other beneficial qualities. Given these results, it is clear that honey has a potential role in the field of tissue engineering and regeneration. Researchers have incorporated honey into tissue engineering templates, including electrospun meshes, cryogels, and hydrogels, with varying degrees of success. This review details the current state of the field, including challenges which have yet to be overcome, and makes recommendations for the direction of future research in order to develop effective tissue regeneration therapies.
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Background: Wound healing in diabetes mellitus is a complex multi-stage process that requires the proper function of multiple systems. The mechanisms of impaired wound healing of diabetic wounds are still poorly understood. Therefore, various interventions are being used for wound management without great success. Bee products have various properties that make them an important addition to the diabetic wound management. Methods: This review summarized previous and recently published papers of the effects of two bee products, propolis and bee venom, on the wound healing. The main results were obtained from preclinical experimentation. Results: Diabetes mellitus compromises immune system, increases infections, impairs wound healing, and affects cells and factors involved in the wound healing. There is an increasing interest in natural products in modern medicine as part of disease management. Bee products are natural substances that others and we have explored some of their biological activities and applications in the treatment of various diseases. Some of these products are bee venom and propolis. These products have analgesic, antioxidant, antimicrobial, and anti-inflammatory properties. In addition, both propolis and bee venom contain considerable amounts of antioxidants that have a great role in accelerating wound healing. Conclusion: There is sound rationality and scientific data for using propolis and bee venom in diabetic wound healing. We believe that topical application of propolis in addition to bee venom might have a place in repairing damaged tissues and accelerating the healing of diabetic wounds.
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Honey bee pollen is considered to be a food, and national pollen standards exist in different countries such as Brazil, Bulgaria, Poland and Switzerland. It is the aim of the present work to review pollen composition and the analytical methods used for the evaluation of high quality bee pollen. Based on the experience of different countries and on the results of published research, we propose quality criteria for bee pollen, hoping that in the future they will be used as world wide bee pollen standards.