Lichen Secondary Metabolites: Bioactive Properties and Pharmaceutical Potential

260 Pages·2019·4.635 MB·English

by  Branislav Ranković

Branislav Ranković E ditor
Lichen
Secondary
Metabolites
Bioactive Properties and
Pharmaceutical Potential
Second Edition
Lichen Secondary Metabolites
Branislav Ranković
Editor
Lichen Secondary
Metabolites
Bioactive Properties and Pharmaceutical
Potential
Second Edition
Editor
BranislavRanković
FacultyofScience
UniversityofKragujevac
Kragujevac,Serbia
ISBN978-3-030-16813-1 ISBN978-3-030-16814-8 (eBook)
https://doi.org/10.1007/978-3-030-16814-8
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Contents
1 LichensasaPotentialSourceofBioactiveSecondary
Metabolites. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
BranislavRankovićandMarijanaKosanić
2 LichensUsedinTraditionalMedicine. . . . . . . . . . . . . . . . . . . . . . . . 31
StuartD.Crawford
3 LichenSecondaryMetabolitesasPotentialAntibioticAgents. . . . . . 99
MarijanaKosanićandBranislavRanković
4 StudiesonAntioxidantPropertiesofLichenSecondary
Metabolites. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
MarijanaKosanićandBranislavRanković
5 InvestigationsofLichenSecondaryMetaboliteswithPotential
AnticancerActivity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
TatjanaStanojković
6 AntigenotoxicEffectofSomeLichenMetabolites. . . . . . . . . . . . . . . 175
HülyaSivas
7 LichenSecondaryMetabolitesasPossibleAntiviralAgents. . . . . . . 199
DamianC.Odimegwu,KennethNgwoke,ChikaEjikeugwu,
andCharlesO.Esimone
8 AntineurodegenerativeandAntidiabeticActivityofLichens. . . . . . . 215
MarijanaKosanićandBranislavRanković
9 FutureDirectionsintheStudyofPharmaceuticalPotential
ofLichens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
NeerajVermaandBhaskarC.Behera
v
1
Lichens as a Potential Source of Bioactive
Secondary Metabolites
Branislav Ranković and Marijana Kosanić
Abstract
Lichens are complex symbiotic associations between fungi and algae which are
important constituents of many ecosystems. The production of various unique
extracellular secondary metabolites known as lichen substances is the result of
thissymbiosis.Thesecompoundsexistwithinthethalliandtypicallyformcrystals
onthesurfaceofthefungalhyphae.Thusfar,morethan800secondarymetabolites
oflichenshavebeendiscovered,mostofthembeingexclusivelypresentinlichens.
In recent date, lichens have been taken up for many researches concerning the
phytochemical and pharmaceutical applications. Lichens and their secondary
metabolites have many pharmaceutical roles, primarily including antimicrobial,
antioxidant,antiviral,anticancer,antigenotoxic,anti-inflammatory,analgesic,and
antipyretic activities. Hence, the present study was undertaken to explain the
lichensastheimportantpotentialsourcesofbioactivesecondarymetabolites.
1.1 The Lichens: Lichenized Fungi
Lichens are association between fungi (mycobiont) and photoautotrophic, algal
partners (photobionts). Since the mycobiont is unique in the symbiotic association
andusuallydominatestheassociation,lichensaretraditionallyclassifiedasalife-form
offungi.About18,500differentlichenspecieshavebeendescribedallovertheworld.
Thefungalpartnersaremostly(98%)Ascomycota(Honegger1991;Gilbert2000),and
theothersbelongtotheBasidiomycotaandanamorphicfungi.Approximately21%of
allfungiareabletoactasamycobiont(Honegger1991);thuslichensformthelargest
B.Ranković(*)·M.Kosanić
DepartmentofBiology,FacultyofScience,UniversityofKragujevac,Kragujevac,Serbia
e-mail:[email protected]
#SpringerNatureSwitzerlandAG2019 1
B.Ranković(ed.),LichenSecondaryMetabolites,
https://doi.org/10.1007/978-3-030-16814-8_1
2 B.RankovićandM.Kosanić
mutualistic group among fungi. Only 40 genera are involved as photosynthetic
partnersinlichenformation:25algaeand15cyanobacteria(Kirketal.2008).
MostcommonphotobiontsarethegeneraTrebouxia,Trentepohlia,andNostoc.
The genera Trebouxia and Trentepohlia are of eukaryotic structure and belong to
the green algae, while the genus Nostoc belongs to the prokaryotic cyanobacteria.
Eukaryotic photobionts are sometimes called phycobionts (90% of lichens), while
cyanobacterialphotobiontsaretermedcyanobionts(10%oflichens).
Inlichenassociationsbothpartnershavebenefit.Themycobionthastwoprinci-
palrolesinthelichensymbiosis:toprotectthephotobiontfromexposuretointense
sunlight and desiccation and to absorb mineral nutrients from the underlying
surface or from minute traces of atmospheric contaminants. The photobiont also
hastworoles:tosynthesizeorganicnutrientsfromcarbondioxideand,inthecaseof
cyanobacteria,toproduceammonium(andthenorganicnitrogencompounds)from
N gas,bynitrogenfixation.Insomeecosystemssuchasdesertsoils,tundraheaths,
2
andDouglas-firforestsofthePacificNorthwestoftheUSA,lichenscanprovidethe
majorinputofnitrogenwhichsupportsotherformsoflife(Hale1983;Nash1996).
Thus, through the lichen partnership, the photobionts are protected and able to
grow in conditions in which they could not grow alone; they also benefit from the
highly efficient uptake of mineral nutrients by the lichen fungi. The fungi, in turn,
obtain sugars and in some cases organic nitrogen from the photosynthetic partner,
enabling them to grow in environments deficient in organic nutrients (Hale 1983;
Nash1996).
A lichen thallus usually consists of layers such as an upper and lower cortex,
algal layer, and medulla (Fig. 1.1). The layers differ in thickness and are better
developedinsomespeciesthaninothers.Fungalhyphaemakeupmostofathallus;
the photobionts are cells only a small percentage (about 7%) of the total volume
(Ahmadijan 1993). There are three main types of thalli: crustose, foliose, and
fruticose(Fig.1.2).Acrustosethalluslacksalowercortexandisgenerallyconsid-
eredtobethemostprimitivetype.ThallioftheLeprariaspeciesdonothavelayers
but consist only of powdery granules. Many crustose lichens stick tightly to the
substratum and appear to be painted on it. Squamules are a specialized type of
Fig. 1.1 A vertical section of lichen thallus showing anatomical features. (a) Homoiomerous
thallus;(b)heteromerousthallus
1 LichensasaPotentialSourceofBioactiveSecondaryMetabolites 3
Fig.1.2 Mainmorphologicalgroupsoflichenthallus.(a)Crustose;(b)foliose;(c)fruticose
crustosethallusandareattachedatonlyoneandtothesubstratum.Afoliosethallus
has an upper and lower cortex, an algal layer, and medulla and is usually loosely
attachedtothesubstratebyhair-likestructurescalledrhizines.Somefolioselichens
havethallithatareattachedtothesubstratebyonlyonecentralpoint.Fruticosethalli
are upright or hanging, round or flat, and often highly branched. The layers of a
fruticosethallusmaysurroundacentralthickcord,asinUsnea,orahollowspaceas
insomeCladoniaspecies(Ahmadijan1993;Nash1996).
Somelichens,suchasCollema,whichhaveNostocasaphotobiont,donotforma
well-organizedthallus(Fig.1.1).Inthesecases,fungalhyphaegrowinsidethethick
gelatinous sheathsofthephotobiont,whichmakes upmuch ofthethallus(Paracer
andAhmadijan2000).
In nature, lichens grow very slowly. Their radial growth is measured in
millimeters per year. Hale (1983) made the following generalization about growth
rates of lichens: most foliose species grow 0.5–4 mm per year, fruticose species
1.5–5mmperyear,andcrustosespecies0.5–2mmperyear.
Lichensgrowpracticallyeverywhere—onandwithinrocks,onsoilandtreebark,
andonalmostanyinanimateobject.Theygrowindesertsandintropicalrainforests,
wheretheyoccuronlivingleavesofplantsandferns.Theyhavebeenfoundonthe
shellsoftortoisesintheGalapagosIslandsandonlargeweevilsinNewGuinea.In
the dry valleys of Antartica, endolithic lichens, such as Buellia and Lecidea, grow
inside sandstone crevices. Dermatocarpon fluviatile and Hydrothyria venosa grow
infreshwaterstreams,andspeciesofVerrucariaarecommonintheintertidalzones
of rocky, ocean shores. Verrucaria serpuloides is permanently submerged marine
lichenthatgrowsonstonesandrocks4–10mbelowmeanlowtideoffthecoastof
theAntarcticPeninsula.Verrucariatavaresiaeisanotherunusualmarinelichenwith
brownalgalphotobiont.DouglasLarsonhasestimatedthatabout8%oftheearth’s
terrestrialsurfaceisdominatedbylichens.Lichensaboundinareaswithhighannual
humidity,suchasthefogbeltzonesofChileandBajaCalifornia.Extensivelichen
populationsalsogrowinthecool,northernforestsoftheworld,wherehundredsof
miles of forest floor are covered with thick carpets of reindeer lichens (Cladonia).
Trees along the coasts of the northwestern United States may be blanketed with
beardlichenssuchasAlectoriaandUsnea(Hale1983;Moe1997;Cox2003).
4 B.RankovićandM.Kosanić
Lichenswithorganizedthallidonotgrowwellinareasthatarecontinuouslywet,
such as tropical rainforests. Only poorly organized species of Lepraria and leaf-
inhabitinglichensarefoundintheseregions.LecanoraconizaeoidesandLecanora
dispersa colonize trees and gravestones in industrial cities and towns, but most
lichenscannottoleratethepollutedatmosphereandpersistentdrynessofurbanareas.
The sensitivity of lichens to atmospheric pollutants such as sulfur dioxide, ozone,
andfluorideshasmadethemvaluableindicatorsofpollutionincitiesandindustrial
regions(Richardson1992).
Interactions between the symbiotic partners allow lichens that live in unusual
environments (Bačkor and Fahselt 2008). Lichens are able to survive in extreme
ecologicalconditions;theycanadapttoextremetemperatures,drought,inundation,
salinity, high concentrations of air pollutants, and nutrient-poor, highly nitrified
environments (Nash 2008). Despite this extreme range of ecological adaptations,
mostlichensaresensitivetochangesoftheirpreferredecologicalconditionsandcan
hardlygrowinnonnativehabitats.
1.2 Lichen Metabolites
Specific conditions in which lichens live are the reason of production of many
metabolites that they provide good protection against various negative physical
and biological influences. Metabolites synthesized by lichens were divided into
twogroups:primaryandsecondary(Lawrey1986).
Theprimary(intracellular)metabolitesincludeproteins,aminoacids,carotenoids,
polysaccharides,andvitamins.Theyaregenerallysolubleinwaterandcanbeeasily
isolated from the lichens by boiling water. Some of the primary metabolites are
producedbyfungiandsomebyalgae.Mostofthesemetabolitesarethenonspecific
and also may occur in free-living fungi, algae, and higher plants. Presence of free
aminoacidsissimilartotheirpresenceintheplants.Ingeneral,theamountofnitrogen
compounds is between 1.6 and 11.4% dry weight of the lichen thallus (Hale 1983).
Carotenoidsaremetabolicproductsofbothsymbiontsandareintherange1.5–24mg/
gdryweightofthetalus.Amongthecarotenoidsinthelichenstalusidentifiedwere
β-caroteneepoxide,α-cryptoxanthin,lutein,astaxanthin.Polysaccharidesandrelated
compounds are present in the lichen in an amount of 3–5% dry weight of the talus
(Culberson 1970). Among vitamins, lichen contains ascorbic acid, biotin,
α-tocopherol, nicotinic acid, pantothenic acid, riboflavin, thiamine, and folic acid.
Vitamins were identified as metabolic products which biosynthesize alga, until the
mushroomsarepoorsourcesofthesecompounds(Hale1983).
Themajorityoforganiccompoundsfoundinlichensaresecondarymetabolites.
Lichensmaycontainsubstantialamountsofsecondarymetabolites,usuallybetween
0.1 and 10% of the dry weight but sometimes up to 30% (Galun and Shomer-Ilan
1988; Stocker-Wörgötter 2008; Solhaug et al. 2009). More than 800 secondary
metabolites known are from lichens, most are unique to these organisms, and only
a small minority occurs in the other fungi or higher plants. All of the secondary
substancesinlichensareoffungalorigin.Thesesubstancesarethecrystalsdeposited
1 LichensasaPotentialSourceofBioactiveSecondaryMetabolites 5
onthesurfaceofthehyphae,whicharepoorlysolubleinwaterandusuallycanbe
isolatedfromthelichensbyorganicsolvents(Bačkorováetal.2012).
Once formed, the lichen secondary metabolites appear to be extremely stable.
Very old herbarium specimens of lichens show no significant reduction in
concentrations of lichen substances (Rundel 1978). In addition, the production of
secondarycompoundsisgeneticallycontrolled(CulbersonandCulberson2001)and
insomeinstancesiscorrelatedwithmorphologyandgeographyinindividualsatthe
speciesandgenuslevels(Egan1986;Zhouetal.2006).
Histologically,lichensecondarymetabolitesaredepositedineitherthecortexor,
morecommonly,themedulla.Themostusualcorticalcompoundsareusnicacidand
atranorin,butanthraquinones,pulvinicacidderivates,andxanthonesmayalsooccur
here.Allofthese,withtheexceptionofatranorin,aretypicallypigmented.Thegreat
majority of lichen substances are deposited in the medulla. Lichen substances are
often expressed differentially in the layers of lichen thallus, and typical cortical
substancescanbedistinguishedfromcompoundsusuallyfoundonlyinthemedulla.
This could be linked with their biological function: the cortical compounds are
regarded as a kind of light filter, which is apparently not a function of compounds
belowthealgallayers(Marques2013).
Lichenssynthesizesignificantamountsofsubstancesonlyinpermissivephysiologi-
calstages.Asaconsequence,theproductioninaxenicculturescandiffersubstantially
from that in nature. Mycobionts grown without their photobionts synthesize specific
secondary lichen compounds under certain conditions (Culberson and Armaleo1992;
Mattsson1994;Stocker-WörgötterandElix2002;Fazioetal.2007;Hageretal.2008)
but can also produce substances that are different from the metabolites found in
symbiosis (Yoshimura et al. 1994; Brunauer et al. 2007). For example, natural lichen
Lecanora dispersa contains 2,7-dichlorolichexanthone as the major secondary com-
pound, but cultured spore isolates, growing without the alga, produced pannarin and
relateddepsidonesinstead(Leuckertetal.1990).Pannarincouldnotbeconfirmedofthe
naturalsourcelichen,butthebiosyntheticpotentialforthisdepsidonewasprovenforthe
speciesbyaherbariumsurvey.Anothersimilarresultistheproductionofatranorinin
Usnea hirta, when cultured in a modified LB medium (Kinoshita 1993), since this
compoundisnotpresentthroughouttheentiregenusUsnea.
Eachlichenmycobiontprefersspeciallyadaptedcultureconditions(suchasnutri-
ent medium, added sugars or polyols, pH, temperature, light, stress) to produce the
specificsecondarymetabolites(Hageretal.2008).Similarly,lichen“tissue”cultures,
inmanycases,canproducesecondarysubstances(Yamamotoetal.1985,1993),but
the chemistry is usually different from the chemosyndrome of the corresponding
natural lichen thalli (Yamamoto et al. 1993). Lichenized Basidiomycotina do not
containlichensubstances(Lumbsch1998).
The distribution patterns of secondary metabolites are usually taxon-specific and,
therefore, have been widely used in lichen taxonomy and systematics (Nordin et al.
2007;Fehreretal.2008;NelsenandGargas2008).However,ithasbeenshownthatthe
similarities in secondary chemistry may not necessarily indicate close phylogenetic
relationships(NelsenandGargas2008).Forexample,XanthoparmeliaandNeofuscelia,
twocloselyrelatedgeneraoftheParmeliaceae,differprimarilyinthepigmentsoftheir
uppercortex:whileXanthoparmeliacontainscrystallizedusnicacid,thecloselyrelated