molecules
Re iew
G een and Sus ainable Valo iza ion o Bioac i e
Phenolic Compounds om Pinus By-P oduc s
Ped o Fe ei a-San os , Elisa Zanuso , Zla ina Genishe a, C is ina M. R. Rocha
and JoséA. Teixei a *
CEB—Cen e o Biological Enginee ing, Uni e si y o Minho, Campus de Gual a , 4710-057 B aga, Po ugal;
[email p o ec ed] (P.F.-S.); [email p o ec ed] (E.Z.); [email p o ec ed] (Z.G.);
[email p o ec ed] (C.M.R.R.)
*Co espondence: [email p o ec ed]; Tel.: +253-604-406
Academic Edi o : Vassiliki O eopoulou
Recei ed: 2 June 2020; Accep ed: 23 June 2020; Published: 25 June 2020


Abs ac :
In Eu ope, pine o es s a e one o he mos ex ended o es s o ma ions, making
pine esidues and by-p oduc s an impo an sou ce o compounds wi h high indus ial in e es
as well as o bioene gy p oduc ion. Mo eo e , he alo iza ion o lumbe indus y esidues
is desi able om a ci cula economy pe spec i e. Di e en ex ac ion me hods and sol en s
ha e been used, esul ing in ex ac s wi h di e en cons i uen s and consequen ly wi h di e en
bioac i i ies. Recen ly, eme ging and g een echnologies as ul asounds, mic owa es, supe c i ical
luids, p essu ized liquids, and elec ic ields ha e appea ed as p omising ools o bioac i e
compounds ex ac ion in alignmen wi h he G een Chemis y p inciples. Pine ex ac s ha e
a ac ed he esea che s’ a en ion because o he posi i e biop ope ies, such as an i-in lamma o y,
an imic obial, an i-neu odegene a i e, an i umo al, ca diop o ec i e, e c., and po en ial indus ial
applica ions as unc ional oods, ood addi i es as p ese a i es, nu aceu icals, pha maceu icals,
and cosme ics. Phenolic compounds a e esponsible o many o hese bioac i i ies. Howe e , he e is
no much in o ma ion in he li e a u e abou he indi idual phenolic compounds o ex ac s om
he pine species. The p esen e iew is abou he eu iliza ion o esidues and by-p oduc s om
he pine species, using eco iendly echnologies o ob ain added- alue bioac i e compounds o
indus ial applica ions.
Keywo ds:
pine; by-p oduc s; bio e ine y; g een p ocess; polyphenols; biological ac i i y; adi ional
applica ions; high alue-added p oduc s
1. In oduc ion
Ag o o es y indus ies a e an impo an pa o he manu ac u ing indus y, and hei g ow h
can help o achie e he objec i es o Eu opean Union (EU) indus ial policy, ac ing in di e en s a egic
a eas, such as inc easing ene gy e iciency, deploying enewable sou ces, ci cula economy, bioeconomy,
and na u al ca bon sinks [
1
,
2
]. Mo eo e , he de elopmen o hese indus ies should also be in line
wi h he 17 sus ainable de elopmen goals by 2030 dic a ed by he Uni ed Na ions; in pa icula , he
ag oindus y can di ec ly impac on a leas 4 o hese goals ela ed o he use o clean ene gy, indus y
inno a ion, esponsible consump ion, and clima e ac ion [3].
Nowadays, 5 billion ons o biomass esidues om ag o o es y and ood indus ies a e es ima ed
wo ldwide and ep esen an emission o 3.3 billion onnes o ca bon dioxide each yea [
4
,
5
]. In he EU,
he o al annual biowas e is es ima ed a a ound 100 million onnes, gene a ing a nega i e ecological
impac [6].
One o he s a egies o he educ ion o gene a ed en i onmen al impac is he euse o indus ial
biowas es o ob ain new na u al ing edien s. Concomi an ly, he g owing in e es in he de elopmen
Molecules 2020,25, 2931; doi:10.3390/molecules25122931 www.mdpi.com/jou nal/molecules
Molecules 2020,25, 2931 2 o 29
o e ec i e/in ensi ied p ocesses and applica ion o g een echnologies o ob ain sus ainable, ecological,
sa e and high-quali y p oduc s has become a eali y [
7
,
8
]. This idea is in close associa ion wi h he
p inciples go e ning he concep o g een chemis y, which a e mainly aimed a educing was es and
p omo ing a mo e e icien use o ene gy and esou ces [9].
The dec ease in he use o “non- ecyclable” ossil de i a i es and he inc ease in he use o
biowas es and by-p oduc s is in he sigh s o he EU and he wo ld, con ibu ing o he educ ion o
he nega i e impac o p ocesses in he en i onmen and he igh agains clima e changes [2]. In his
sense, he use o di e en plan by-p oduc s as sou ces o ma e ials, bio uels, ene gy, and bioac i e
compounds has come o be explo ed ollowing he concep o bio e ine y, con ibu ing o a ci cula
economy [6].
The p esen e iew ocuses on he app ecia ion o di e en g een ex ac ion s a egies ela ed
o he eco e y o high added- alue compounds (such as polyphenols) om pine by-p oduc s, hei
po en ial bioac i i ies, and possible indus ial applica ions.
2. Bio e ine y and Lignocellulosic By-P oduc s
Resou ces deple ion, was e accumula ion, and clima e change a e a combina ion o o ces d i ing
he need o he sus ainable p ac ices we a e acing nowadays. Addi ionally, u baniza ion and
popula ion g ow h a e causing he global ene gy demand o be in con inuous ise. Wi h he ene gy
demand inc easing, he necessi y o de achmen om ossil uels and he ansi ion o enewable
esou ces is manda o y o educe he en i onmen al p oblems. Ene gy esou ces such as biomass, wind,
and sola ene gy can mee he ene gy equi emen s i la ge-scale echnologies a e well de eloped [
10
].
In his sense, bio e ine y is analogous o ossil uel e ine y. The bio e ine y e m da es back o
1980. Since hen, se e al de ini ions ha e been conside ed. These de ini ions a e based on he ype o
eeds ock used, ype o p ocesses, and ype o p oduc s ob ained [
11
]. In gene al, he bio e ine y concep
is he syne gy o echnologies ha con e biomass in o hei building blocks o p oduce a a ie y
o bio uels, chemicals, and high added- alue compounds. He eo , he de elopmen o a sus ainable
p ocess in ol es no only he use o biomass bu also implies educing he use o ha m ul chemicals,
ansi ion o g eene p ocesses, e icien use o ene gy, and elimina ion o was es (Figu e 1) [9].
Figu e 1. Pine alo iza ion unde bio e ine y concep .
Molecules 2020,25, 2931 3 o 29
E hanol is a well-known bio uel p oduc o he second gene a ion bio e ine y. Second gene a ion o
lignocellulosic bio e ine y usually begins wi h he p e ea men o he biomass in o de o inc ease he
diges ibili y o cellulose, o solubilize he hemicellulose, and o eloca e he lignin [
12
]. P e ea men s
can be mechanical, chemical, physicochemical, o biological [
13
]. A e wa d, o libe a e he e men able
suga s (i.e., monosaccha ide uni s) om he p e ea ed biomass, acid o enzyma ic hyd olysis p ocesses
a e applied [
14
]. Then, he e men a ion o he ob ained suga s o ob ain e hanol can be ca ied ou
using mic oo ganisms as yeas o bac e ia [
15
,
16
], whe e, in an in eg a ed bio e ine y, e hanol can also
be conside ed as a p ecu so o chemicals, hyd oca bon uels, and a oma ic compounds [
17
]. Hence,
he esea ch and de elopmen o sus ainable p ocesses a e g owing no only o bio uels bu also o
he high added- alue compounds han can allow an economically iable p ocess (Figu e 1).
Cu en ly, lignocellulosic biomass has been la gely s udied as a po en ial subs a e in e men a ion
p ocesses, and mainly o bio uel p oduc ion. Ne e heless, inno a i e and new eme ging echnologies
a e being s udied o inc ease he ob ainmen o high- alue compounds o in e es , pa icula ly bioac i e
ones. The eco e y o hese o high- alue compounds is linked o he bio e ine y concep and he g een
chemis y p inciples. Lignocellulosic biomass (in which pine by-p oduc s may be included) is mos ly
conside ed as a esidue om c ops as s aw, suga cane bagasse, co n s o e , and wood was e. Cellulose
is he majo componen o he lignocellulosic ma e ials, ollowed by hemicellulose and lignin. Cellulose
is he wo ld’s mos abundan biopolyme made up o glucose uni s. Applica ions o cellulose ex ac ed
om lignocellulosics include he manu ac u e o cellulosic ibe and nanoc ys alline cellulose in a wide
ange o indus ies such as au omo i e, ex ile, and medicine due o he s eng h on i s s uc u e,
a ailabili y, modi iable su ace, enewabili y, and low cos [
18
,
19
]. Hemicellulose is he second mos
abundan polysaccha ide in lignocellulosic biomass mainly composed by monome ic uni s as xylose,
mannose, a abinose, glucose, galac ose, and acids such as u anic acid [
20
]. Hemicellulose and speci ic
a ge p oduc s om hemicellulose a e used in a a ie y o a eas as ood, medicine, and chemicals due o
he biocompa ibili y and bioac i i y p ope ies hey show [
20
]. Pine sawdus has been used o p oduce
le ulinic, o mic, and ace ic acid and u u al o m hemicellulose ex ac ed by s eam explosion [
21
]. In
addi ion, pinewood (Pinus elda ica) p e ea ed wi h dilu e sodium hyd oxide was used o p oduce
e hanol om he p e ea ed solid whe e he solubilized hemicellulose ac ion was used o p oduce
biogas [
22
]. The hi d main componen o lignocellulosic ma e ials is lignin, which is an amo phous
phenolic polyme ha p o ides mechanical s eng h and igidi y o plan s [
23
]. In he bio e ine y
p ocess, lignin canno be used as a subs a e o e men a ion as i con ains no suga s. The e o e, a wide
a ea o esea ch is on lignin alo iza ion. Lignin is mainly used o gene a e hea and elec ici y due o
he high hea ing alue al hough o he applica ions a e possible, including he use as a p ecu so o
ca bon ibe syn hesis, esins, and low molecula weigh a oma ic and phenolic compounds [
24
,
25
].
Nowadays, he mode n polyme indus y om na u al sou ces o a oma ic compounds is limi ed due
o he high p ices o he inal p oduc . He e, lignin plays an impo an ole, since phenolic compounds
can be ob ained om lignin decons uc ion [26].
His o ically, wood has been a majo ene gy sou ce o human beings. Fo es biomass is he mos
abundan eeds ock on ea h, ep esen ing 89.3% o he o al biomass [
27
]. In Eu ope, o es a ea
is one o he mos impo an enewable esou ces, ep esen ing nea 5% o he wo ld’s o es and
co e ing 43% o i s land, comp ising close o 182 million hec a es o o es . Fo es is also conside ed as
a esou ce o imp o ing li e quali y and job gene a ion [
28
]. Wood biomass can be densi ied in o solid
uels, as pelle s, o con e ed in o hea , elec ici y, bio uels, and o he biop oduc s h ough a a ie y o
chemical, he mochemical, and biochemical p ocesses [
29
]. On he o he hand, he lumbe indus y
gene a es a conside able amoun o was e ha includes lea es, ba ks, sawdus , chips, cones, esins, and
b anches. These esidues a e no usually well alued and a e h own ou , bu ned, o used o animal
bedding, al hough hey can be a p o i able sou ce o high added- alue compounds [
30
]. The ein,
wood biomass esidues inc ease hei o e all alue due o he me aboli es ha a e p esen in lowe
abundance compa ed wi h cellulose, hemicellulose, and lignin. These ex ac i e compounds combine
alkaloids, waxes, phenolics, pec ins, esins, and essen ial oils [
31
], and hey a e o g ea impo ance
Molecules 2020,25, 2931 4 o 29
conside ing he wide indus y applica ions, mo e p ecisely, in ood and pha maceu ical indus ies due
o he an ioxidan , an imic obial, an i-in lamma o y, and an i umo al e ec s hey show [32].
3. Pine as Feeds ocks
This wo k is mainly ocused on he alo iza ion o he Pinus species (and i s by-p oduc s), which
a e e e g een ees o esinous coni e s g oup om he Pinaceae amily. In he EU, he e a e mo e han
14 di e en species, ep esen ing one o he la ges o es occupa ions. Table 1desc ibes he main Pinus
species dis ibu ed in he Eu opean coun ies acco ding o he “Eu opean o es gene ic esou ces
p og am (EUFORGEN)” [33]. In Po ugal, pine o es s a e he hi d o es o ma ion a e eucalyp us
and co k oaks, wi h an a ea o app oxima ely 1 million hec a es, ep esen ing an impo an pa o he
o al o es , abou 23% [34].
Table 1.
Pinus ees species implemen ed in Eu opean coun ies, as well as i s geog aphical dis ibu ion.
La in Name Common Name Geog aphical Dis ibu ion
Pinus syl es is Sco s pine All coun ies o Eu opa and Asia
Pinus nig a Eu opean black pine Moun ain a eas o Eu ope, Uni ed S a es, and Asia Mino
Pinus b u ia B u ia pine Eas e n Coas o he Medi e anean (Tu key, G eece, I aly)
Pinus pinas e Ma i ime pine Wes e n Medi e anean Sea, Cen al and Sou he n Eu ope,
and No h A ica
Pinus halepensis Aleppo pine Coas al a eas o he Wes e n Medi e anean egion, Sou he n
F ance and I aly, and No h A ica
Pinus cemb a Swiss s one pine Con inen al Alps and egions o he Ca pa hian Moun ains
Pinus uncina a Moun ain pine Moun ains o Wes e n Eu ope, No he n Eu ope, and
Medi e anean
Pinus pinea S one pine Medi e anean Basin, ex ending om Po ugal o Sy ia
Pinus s obus Whi e pine Eas e n No h Ame ica and Ca pa hian Moun ains in Czech
Republic and Sou he n Poland
Pinus mugo Moun ain pine Moun ains o Cen al and Eas e n Eu ope
Pinus held eichii Bosnian pine Sou he n and Wes e n pa o he Balkans, nea he
Medi e anean basin
Pinuscon o a Lodgepole pine Wes e n No h Ame ica, Eu ope, and New Zealand
Pinus peuce Macedonian pine Moun ain a eas o he Balkan Peninsula
Pinus adia a Mon e ey pine Cen al Coas o Cali o nia, Aus alia, New Zealand, Mexico,
A gen ina, Chile, U uguay, Kenya, Spain, and Sou h A ica
The chemical composi ion o pine and i s cons i uen s (wood, ba k, lea es, cones, seeds, and esin)
a ies depending on he Pinus ee and also on many o he ac o s, such as geno ypic, ecological, and
seasonal, among o he s [
35
]. The me hodology used o he de e mina ion o chemical composi ion o
plan esou ces is also a ac o o conside , since di e en me hods lead o di e en esul s [36].
The gene al chemical/nu i ional composi ion o pine by-p oduc s has been desc ibed by se e al
au ho s (wood [
37
–
42
], ba k [
43
–
47
], needles [
48
,
49
], cones [
41
,
50
], seeds (nu s) [
51
–
53
], and esin o
oleo esin [54,55]) and is summa ized in Figu e 2.
Molecules 2020,25, 2931 5 o 29
Figu e 2. Gene al chemical/nu i ional composi ion o pine by-p oduc s.
Pine Applica ions
A p esen , ag o o es y esidues and by-p oduc s a e mainly used as combus ion eeds ock o
bio uels p oduc ion [
56
]. The mos impo an biomasses a e ob ained om lumbe indus y (ba k
and sawdus ) o o es ac i i ies, he esidues om a ms and ag o-business, he o ganic ac ion o
municipal solid was es, and he plan s delibe a ely g own o ene ge ic pu poses. In his sense, i is
impo an o educe and gi e a “second li e” o hese esidues, mo ing o “ze o was e”.
The Pinus plan is e y impo an economically, as i is conside ed good eeds ock o he
bioeconomy (Figu e 1) [
57
]. In i s na u al en i onmen , i has an impo an p o ec i e unc ion, such as
imp o ing wa e in il a ion, p e en ing soil e osion on d y slopes, and se ing as a windb eak [
33
].
T ees a e also used as o namen al plan s in u ban and indus ial con ex s. O he uses include Ch is mas
ees and uelwood.
In e es ingly, in a s udy by Ehn and co-wo ke s [
58
], i has been ound ha pine o es a oma ( o
i s con en in ola ile compounds, e penes) can limi clima e change, p e en ing he global wa ming.
The main indus ial ac i i ies a e ela ed o he usage o pine wood and wooden p oduc s,
including sawmills, wood panels, cellulose pulp and pape p oduc ion, wood uels, ca pen y, packing,
and wood u ni u e [
33
]. These eeds ock, hei componen s, and hei by-p oduc s a e conside ed
a good sou ce o wood bio e ine ies, ans o ming he lignocellulosic ac ions in o bio uels, chemical
p oduc s, and composi e ma e ials, as p e iously men ioned [57].
Pine ba k, he by-p oduc ob ained in la ge quan i ies ha is p oduced when wood is ans o med,
is almos exclusi ely used as uel, being also subjec ed o compos ing o illing subs a e in nu se ies,
u ilized o co e in public ga dens, o simply h own away on landscapes [
44
,
59
]. Nowadays, his
by-p oduc has been used as low-cos and g een al e na i es was e-based bioso ben s o he emo al
o a wide ange o wa e pollu an s [60].
The pine lea es (needles) a e no mally used in ag icul u e o en ich he soil, and he seeds a e
used o human consump ion because hey a e highly nu i ious and much app ecia ed by consume s
in cooked/p epa ed dishes ( ood indus y) o simply as edible pine nu s. The esins, a p oduc esul ing
om he exploi a ion o hese species, a e mo e egula ly used as a sealan , glue, a nish, and also as
a sol en and pain hinne ( u pen ine oil) [55,57,61].

Molecules 2020,25, 2931 6 o 29
In addi ion o he “ adi ional” uses o hese by-p oduc s, i is impo an o ake ad an age o
hese bio- esou ces o c ea e high alue-added p oduc s.
Cu en ly, he ag o o es y by-p oduc s ha e been inc easingly exploi ed o isola e biocompounds
wi h high indus ial in e es . S udies using na u al ma ices as a po en ial sou ce o bioac i e
compounds ha e been published in ecen decades [
7
,
62
–
67
]. Fo ins ance, in a new e iew pape [
68
],
he au ho s epo ha in addi ion o ui s and ege ables, ee ba ks a e ich in phenolic compounds
wi h excellen biological p ope ies (such as an ioxidan , immunos imula o y, an icance , an ibac e ial,
an i-in lamma o y, an imu agenic, e c.) and may used o ob ain unc ional ing edien s.
Pine ba k is one o he mos sough a e sou ces o an ioxidan biocompounds o na u al o igin.
The ex ac s ob ained om his by-p oduc a e mos ly composed o phenolic compounds wi h high
biological ac i i y [
46
,
59
,
62
,
69
–
72
]. Nowadays, he e a e nume ous s udies epo ing he applicabili y
o pine bioac i e ex ac s in a ious a eas, such as heal h ca e, ood, ag ochemical, and o he s [
73
–
75
].
One o he mos p omising applica ions o hese ex ac s is in he p ese a ion and en ichmen o oods,
hus eplacing syn he ic an ioxidan s, as well as a nu aceu ical, cosmeceu ical, o pha maceu ical.
The pine wood/sawdus ex ac i es, ich in phenolic an ioxidan compounds, ha e a po en ial o
ood and pha maceu ical applica ions, such as p ese a i es o nu aceu icals [40,76].
Pine a s, a by-p oduc o pine wood and ba k, a e known o con ain icyclic di e penoid esin
acids, icyclic di e pene hyd oca bons, alkylphenan h enes, and a y acids. This wa e - esis an
by-p oduc has a wide ange o applica ions, o example, as a mul ipu pose adhesi e, sealan , and in
medicine [77,78].
Knowing he chemical composi ion and physicochemical p ope ies, pine seeds o nu s appea o
ha e a posi i e e ec on human heal h [
52
,
53
]. The seed lipids, ich in linoleic acid, ha e a bene icial
e ec on blood p essu e and choles e ol. The a y acid composi ion and he ela i ely high polyphenol
con en p esen high p o ec ion agains oxida i e s ess. In his sense, pine seeds can po en ially be
used in he ood indus y and o he non- ood indus ies, such as pha maceu ical and cosme ics [
79
–
81
].
Oleo esins a e widely used in he syn hesis o pe umed compounds o cosme ics, essences
as addi i es o ood and be e ages, ood p o ec ion (an imic obial), bioinsec icides (high
epellen ac i i y), apping g een chemicals, bio uels, and ca bon seques a ion om mul ipu pose
ees [54,55,57,61].
In e es ingly, his sea ch o unc ional ex ac s, new na u al molecules, and he c ea ion o new
high alue-added p oduc s has inc eased he use/s udy o ag o o es y by-p oduc s and esidues,
including pine ba k, sawdus , lea es, seeds, and esin. This makes i possible o po en ially b ing hese
“was es” back o he ma ke .
4. Ex ac ion P ocesses o Phenolic Compounds Reco e y
The eco e y o bioac i e and unc ional pu i ied biomolecules o ex ac s om plan ma e ials is
an impo an s ep o enable he euse o na u al esou ces o subsequen applica ion in pha maceu ical
and cosme ic p oduc s, ood en ichmen and p ese a i es, die a y supplemen s, and nu aceu icals.
The ex ac ion p ocess o na u al ex ac s depends on se e al ac o s, including he applied
ex ac ion echnique, he pa ame e s associa ed wi h he echnique (such as empe a u e, ime, and he
ex ac ion sol en ), and he aw ma e ials composi ion [
63
]. I is known ha he phenolic compounds
a e me aboli es p esen in he cell acuoles [
82
]. The e o e, i is also impo an o p omo e he
opening o po es o e en he up u e o he cell wall o acili a e he elease o he compounds in o he
ex ac ion medium.
In his sense, i is impo an o s udy all a iables o he p ocess in o de o maximize he po en ial
o he ex ac ion me hod, de eloping a highly e icien p ocess [
8
]. On he o he hand, all a iables
in he p ocess ha e o make i possible o ob ain a sa e and high quali y inal p oduc (eco-ex ac ),
in addi ion o maximizing he ex ac ion o he compounds o in e es . Figu e 3illus a es he main
p inciples o an e icien ex ac ion p ocess, ollowing he concep o g een ex ac ion.
Molecules 2020,25, 2931 7 o 29
Figu e 3.
P inciples o e icien p ocess o ob aining na u al ex ac s. Adap ed om Chema e al. [
8
].
4.1. Ex ac ion Sol en s
The educ ion use o haza dous sol en s is also conside ed one o he p io i ies o he EU policy
o he 2010 o 2050 pe iod [
7
]. Nowadays, ex ac ion using con en ional o ganic sol en s is he
mos commonly used p ocedu e o p epa e ex ac s om plan ma e ials due o hei ease o use,
e iciency, and wide applicabili y. The e iciency o he ex ac ion me hods depends on he choice o
he sol en , since sol en s wi h di e en pola i ies a e needed o he isola ion o compounds wi h
di e en chemical cons i u ion. In addi ion, i is di icul o de ine a single me hod o he e icien
ex ac ion o all compounds, since he pola i ies o he molecules o be ex ac ed a y [63].
A sui able sol en has o be able o ob ain sa e and high-quali y ex ac s and o p ese e he
biological e ec s o he ex ac ed compounds wi hou exhibi ing oxici y when consumed. Fu he mo e,
i should be ecyclable and eusable, p e en ing nega i e en i onmen al e ec s. O he pa ame e s,
such as lammabili y, explosi eness, ola ili y, mass ans e , and (in)abili y o dissocia e he complex
ex ac should be conside ed [
65
]. The ex ac ion yield depends no only on he sol en used bu also
on se e al o he ac o s such as sample/sol en a io, empe a u e, ex ac ion ime, s i ing, and aw
ma e ial composi ion [83].
Con en ional sol en s om “non-na u al”/pe oleum esou ces, such as me hanol, e hanol,
ace one, e hyl ace a e, dichlo ome hane, hexane, e c. and hei aqueous solu ions ha e been used
o he ex ac ion o bioac i e compounds om plan ma e ials. Se e al s udies ha e been done
demons a ing he impo ance o hese sol en s in he eco e y o na u al molecules and ac i e
ex ac s om di e en plan s and by-p oduc s [
65
,
84
–
86
], including he lignocellulosic by-p oduc s [
87
].
Resea che s also s udied he in luence o hese di e en sol en s in ob aining an ioxidan phenolic
compounds om pine by-p oduc s, and depending on he sol en used, he ex ac ed ac ion (ex ac
composi ion) is di e en [
59
,
85
,
88
]. Fo example, in a wo k by Venka esan and collabo a o s [
85
],
he impac o di e en ex ac ion sol en s (such as e hanol, me hanol, isop opanol, ace oni ile, and
ace one) was analyzed o ob ain phenolic ex ac s wi h an ioxidan ac i i y om Pinus densi lo a ba k.
Thei esul s showed ha low concen a ions o e hanol and ace oni ile a e a o able o he ex ac ion
o phenolics wi h high an ioxidan ac i i y. In ano he s udy, using Pinus ni u i, me hanol was mo e
e icien han o he sol en s such as e hanol, hexane, and e hyl ace a e, showing an enhanced ex ac ion
a e o phenolic and la onoid compounds wi h highe biological ac i i ies [88].
I is known ha wa e is an e icien sol en o he ex ac ion o a ious compounds, due o i s
p ope ies and hanks o he ac ha wa e is easily a ailable, sa e, non- oxic, non- lammable, and
en i onmen ally iendly [
8
]. In his sense, i is conside ed he cleanes /g eenes sol en (apa om
Molecules 2020,25, 2931 8 o 29
he use o no sol en , which is he g eenes ), acco ding o he p inciples o g een chemis y [
64
,
89
].
Howe e , i is no sui able o he ex ac ion o less pola subs ances.
O he possible en i onmen al iendly sol en s’ op ion is o eplace pe oleum-based sol en s by
“bio-sol en s”. Fo ins ance, “bioe hanol” can be p oduced om bio esou ces, by e men a ion. This
second-gene a ion sol en could be made cos -compe i i e by he de elopmen o bio e ine y-based
p ocesses o he in eg al use o lignocellulosic biomass, subs i u ing e hanol ob ained om pe oleum
de i a i es [90].
As al e na i es o con en ional sol en s, he use o g een sol en s such as ionic liquids (ILs)
and na u al deep eu ec ic sol en s (NADES) is eme ging, in o de o make he ex ac ion p ocess
eco- iendly and mo e e ec i e [
91
]. In gene al, ILs and NADES a e de i ed om cheap, abundan ,
low oxic, and biodeg adable na u al componen s [
6
,
7
]. NADES can be de ined as “mix u es o pu e
na u ally occu ing compounds ha p esen an eu ec ic poin empe a u e below an ideal liquid
mix u e” [
6
,
92
]. ILs a e liquid mol en sal s a empe a u es below 100
◦
C composed by ca ions and
o ganic o ino ganic anions wi h exclusi e and adjus ed physicochemical p ope ies [93].
Howe e , a lack o in o ma ion on he biological ac i i y and oxici y o he ob ained ex ac s
limi s he use and indus ial applica ions o ILs and NADES [
7
], leading o hese sol en s no being
egula ed by he Fede al D ug Adminis a ion (FDA) [
94
]. Fu he mo e, al hough hey can be uned
o enhanced a ini y owa d he compound o in e es , hei sepa a ion om he inal mix u e may be
hinde ed by he high boiling poin cha ac e is ic o hese sol en s.
Mu ado and collabo a o s [
95
] summa ize he main chemical cons i uen s o hese ILs and
NADES and men ion some wo ks whe e hey a e applied in he ex ac ion o an ioxidan compounds,
such as phenolic compounds and ca o enoids, among o he s. Speci ically, ILs and NADES ha e been
applied o he phenolic compounds and o he an ioxidan compounds ex ac ion om lignocellulosic
biomass and ag i- ood was es [4,6,93,96–98].
In he case o pine plan s as eeds ock, he p ocess o ex ac ing bioac i e compounds wi h added
alue (such as phenolics) using hese g een sol en s is no widely explo ed. In a ecen s udy, ILs
we e combined wi h enzymes and mic owa e echnology o p omo e cell wall dis up ion o he
ex ac ion o essen ial oil and p ocyanidins om pine cones o Pinus ko aiensis [
99
]. Howe e , he e a e
no epo s using ILs and NADES as al e na i e sol en s o ex ac ion o bioac i e molecules o o he
pa s o pine plan , despi e he ad an age hey showed o ob aining unc ional compounds in o he
lignocellulosic esidues.
4.2. Ex ac ion Technologies
Con en ionalme hodso ex ac ion,suchas hesolid–liquidme hod,hyd odis illa ion,mace a ion,
and Soxhle equi e he use o la ge amoun s o wa e o o ganic sol en s, agi a ion, long ex ac ion
ime, high empe a u es, and ene gy consump ion, as well as he gene a ion o a conside able quan i y
o was es [8,100,101].
The need o ob aining g eene , sus ainable, and iable p ocesses has led scien is s and indus ies
o de elop new p ocesses in ull co espondence wi h he g een ex ac ion concep [
102
,
103
]. In his
con ex , he sea ch o al e na i e ex ac ion echnologies wi h en i onmen al and economic ad an ages,
aking in o accoun he cha ac e is ics o he inal p oduc s has eme ged [
104
]. As a esul , echniques
such as ul asound-assis ed ex ac ion (UAE), mic owa e-assis ed ex ac ion (MAE), supe c i ical luid
ex ac ion (SFE), p essu ized liquid ex ac ion (PLE), and ohmic hea ing (OH) elec o echnology ha e
been de eloped, op imized, and applied o imp o e he ex ac ion p ocess o an ioxidan phenolic
compounds om plan esou ces, such as pine by-p oduc s (Table 2).
In he ollowing sub-sec ions, a b ie in oduc ion o hese ex ac ion echnologies and some
examples o hei applica ion in ob aining phenolic compounds om pine by-p oduc s will be p esen ed.
Molecules 2020,25, 2931 9 o 29
4.2.1. Ul asound-Assis ed Ex ac ion
Ul asound p oduces high-in ensi y sound wa es ( ypically highe han 20 kHz) [
104
]. The
ope a ion mechanism o UAE is based in p essu e a ia ions ha o m mic obubbles esul ing in
mic o u bulence and a high collision o pa icles. The collapse o mic opa icles caused by ul asound
wa es can p omo e highe pene a ion o he sol en in o he cellula ma e ial causing he cell walls
dis up ion and inc easing he elease o in acellula compounds in o he ex ac ion medium [
105
,
106
].
UAE is an al e na i e echnology wi h ad an ages compa ed o con en ional echniques, since less
p ocessing ime, low sol en usage, and lowe ex ac ion empe a u es a e equi ed, p ese ing
hea -sensi i e compounds. In addi ion, i leads o an inc ease in ex ac ion yield, equi ing less ene gy
in he p ocess [
106
]. Due o i s ad an ages, ul asound echnology is men ioned as an eco- iendly and
cheap p ocess and can be easily implemen ed o ex ac phenolic compounds om plan s and plan
by-p oduc s [76,107–110].
In he las decade, UAE has been used o ob ain ex ac s ich in phenolic compounds om pine
by-p oduc s. In a s udy o Liazid and co-wo ke s [
111
], UAE was used o ob ain phenolic ex ac s
om seeds o wo pine species (Pinus ma i ima and Pinus d’Alpes). The esul s o his wo k showed ha
he applica ion o ul asound wa es, using wa e as a sol en a 75
◦
C du ing 20 min, doubled he
eco e y o phenolic compounds compa ed o a con en ional mace a ion echnique, inc easing he
an ioxidan ac i i y o hese ex ac s. Using he ba k o he Pinus adia a as a aw ma e ial, Asp
é
and
collabo a o s [
112
] e i ied ha he syne ge ic e ec o ul asounds (35 kHz/85 W) wi h ace one 70%
( / ) allows he o ma ion o po es in he ma ix cells, p omo ing he apid up u e o he cell wall,
acili a ing he ex ac ion o phenolic compounds, and d as ically educing he ex ac ion ime ( om
180 min o con en ional ex ac ion in a wa e ba h o Soxhle , o 6 min when using UAE).
In ano he s udy, au ho s used ul asound echnology in combina ion wi h me hanol 70% ( / ) as
a sol en o ex ac phenolic compounds, such as la onoids om lea es (needles) o ou di e en
pine species (Pinus peuce,P. nig a,P. mugo and P. syl es is) [
113
]. UAE p o ed o be a po en ial ool
o he sus ainable eco e y o phenolic compounds om pine lea es, wi hou using empe a u e in
he p ocess.
Recen ly, Meullemies e and co-wo ke s [
76
] epo ed ha he UAE, in addi ion o inc easing he
ex ac ion o phenolic compounds om ma i ime pine wood (sawdus was e) by 40% compa ed o
con en ional ex ac ion echniques (solid–liquid), also allowed educing he ime o he p ocess. On
he o he hand, hey also epo ed ha UAE is a scalable echnique and can be applied indus ially o
ob ain bio- unc ional ex ac s.
4.2.2. Mic owa e Assis ed Ex ac ion
MAE is a hea ing p ocess using elec omagne ic wa es o equency be ween 300 MHz and
300 GHz ha in e ac wi h samples o ex ac analy es om a ma ix o a sol en . The mic owa e
i adia ion inc eases he in e nal p essu e o he plan cells by hea ing he cells om he inside, leading
o cell dis up ion and eleasing he compounds o in e es . Some o he ad an ages o MAE a e a lowe
ime o ex ac ion compa ed wi h o he ex ac ion p ocesses, he possibili y o mul iple ex ac ions,
low sol en olume, an a ainmen o high empe a u es, and mo e e ec i e, uni o m and selec i e
hea ing [
107
,
114
]. To ha e be e ex ac ion yields, i is impo an o conside he capabili y o he
sol en o abso b mic owa es, as i can be a d awback when he sol en lacks he capaci y o ene gy
abso p ion. Fu he mo e, he hickness o he sample o be hea ed may also be a d awback, pa icula ly
in he scalabili y o he ex ac ion p ocess, as he abili y o mic owa es o pene a e a sample is limi ed.
Liazid e al. [
111
] s udied he ex ac ion o phenolic compounds om Pinus pinas e seeds using wa e
as sol en and demons a ed ha MAE p oduces ex ac s wi h g ea polyphenols con en , since i can
achie e high empe a u es, which is a decisi e ac o in phenolic compounds ex ac ion, as mos o
hese p ocesses a e empe a u e dependen . In his wo k, he polyphenolic ex ac s ob ained a 75
◦
C demons a ed high an ioxidan ac i i y. In ano he wo k, he ex ac ion ime o ob ain phenolic
compounds om Pinus adia a ba k was educed by 98.3% using MAE compa ed wi h he Soxhle
Molecules 2020,25, 2931 16 o 29
depends on he pa icle size [
76
]. The pa icle size has a di ec e ec on he amoun o he polyphenol
ex ac ed. The smalle he pa icle size is, he mo e ex ac s a e ob ained (bes esul s we e egis e ed
o size 0.4 mm). Howe e , he e is no impac on he na u e o he ex ac and on he ypes o he
compounds ex ac ed [
115
]. The e is a lowe limi o he pa icle size beyond which he quan i y o
ex ac ed polyphenols dec eased. I was egis e ed ha e y ine pa icles s ayed in suspension a he
su ace o he sol en and he e o e we e no subjec ed o p ope ex ac ion [76].
The ex ac ion o polyphenols would also depend on he solid/liquid a io. Meullemies e e al. [
76
]
ound he op imum a io o be abou 6 g o d y ma e ial/100 mL; when concen a ions we e highe
han 7.5 g o d y ma e ial/100 mL, he ma i ime pine wood abso bed all a ailable liquid.
Eigh een phenolic compounds we e iden i ied in he ex ac s o P. pinas e by Fe ei a-San os and
co-wo ke s [
45
,
59
]. In one o he s udies, he au ho s ied o unde s and he ac ion o he ype o sol en
(wa e and e hanol) and me hod o ex ac ion (con en ional o ohmic hea ing) o e he chemical p o ile
o he ex ac s. Ex ac s made wi h he di e en sol en s we e ound o be s a is ically di e en in e ms
o con en o phenolic compounds [
59
]. The an ioxidan ac i i y o he ex ac s we e always highe in
he hyd oe hanolic ex ac s compa ing wi h he aqueous ex ac s. Mo eo e , signi ican co ela ions
we e ound be ween o al phenolic con en and an ioxidan ac i i ies o he ob ained ex ac s [
59
]. In
a second s udy, om he same au ho , pine ba k ex ac s made wi h di e en concen a ions o e hanol
( om 0% o 90%) we e e alua ed o hei bioac i i ies (an ioxidan , an imic obial, and an idiabe ic)
and
in i o
cell iabili y (in no mal and cance cell lines). The s udy demons a ed ha he pine ba k
ex ac s ha e high po en ial an ioxidan , an idiabe ic, and an imic obial ac i i ies, especially when
made wi h 50% and 70% o e hanol [
45
]. Mo eo e , he au ho s concluded ha pine ba k ex ac s ac
selec i ely on cance cells, as hese a e nega i ely selec ed and he non- umo cells a e no .
In gene al, bo h s udies [
45
,
59
] showed ha he compounds wi h he highes concen a ions in
all samples we e ellagic acid and axi olin. The concen a ions o ellagic acid accoun ed o be ween
9.0% and 50% o he o al phenolic compounds, while axi olin accoun ed o be ween 15% and 42% o
he o al phenolic compounds. Indi idual concen a ions o phenolic compounds such as ca echin,
axi olin, que ce in, ca eic acid, o-couma ic acid, e ulic acid, and ellagic acid in he ex ac s made
wi h 50% e hanol we e almos wice as high as in he co esponden ex ac s ob ained wi h wa e .
The e a e no many s udies showing he iden i ica ion and e en less s udies showing he
quan i ica ion o polyphenols in ex ac s om Pine species. The ex ac s a e ob ained mos ly om he
pine ba k, and ewe a e ob ained om needles (Table 3). The chemical composi ion o he ex ac s
depends on he ype o pine used (species, loca ion), on he pa o he plan , on he me hod o
ex ac ion, and on he sol en . Fo example, he main g oup o polyphenols compounds ound in he
P. syl es is is he g oup o s ilbenes [
151
], while in P. pinas e , he main g oup o compounds a e he
la onoids [59].
Table 3. Indi idual phenolic compounds ound in pine by-p oduc s and hei epo ed bioac i i ies.
Name Chemical
Fo mula
Concen a ion
Range (mg/g) Bioac i i ies Re e ence
NEEDLES
Epica echin C15H14O61.5 an ioxidan [152,153]
p-Couma ic Acid C9H8O32.3
an ioxidan ,
an i-in lamma o y,
hepa op o ec i e and
enop o ec i e,
an i-neu odegene a i e,
an i-choles e olemic,
imp o e insulin esis ance,
an i- y osinase,
an imic obial
[152,154–156]

Molecules 2020,25, 2931 17 o 29
Table 3. Con .
Name Chemical
Fo mula
Concen a ion
Range (mg/g) Bioac i i ies Re e ence
SEEDS
P o oca echuic Acid C7H6O40.5
an i- y osinase,
an imic obial, and
an i-in lamma o y ac i i ies
[156,157]
Ca echin C15H14O60.5 hepa op o ec i e ac i i y [145,157]
Epigalloca echin Galla e C22H18O11 0.5 an imic obial, an ioxidan ,
pho op o ec i e [145,157]
Vanillic Acid C8H8O40.9 an i-in lamma o y,
neu op o ec i e [157,158]
Sy ingic Acid C9H10O51.0
ca diop o ec i e,
an ioxidan , an imic obial,
an i-in lamma o y, neu o
and hepa op o ec i e
ac i i ies
[157,159]
Epica echin C15H14O61.3 an ioxidan [157]
Taxi olin C15H14O71.7 an ioxidan , an icance ,
an i-in lamma o y [157]
Cinnamic Acid C9H8O20.1
an i- y osinase,
an imic obial, and
an i-in lamma o y
[156,157]
E iodic yol C15H12O63.8 an i-in lamma o y [157,160]
m-Couma ic Acid C9H8O3 aces no ound [157]
BARK
Gallic Acid C7H6O5 aces–5.5
an i-in lamma o y,
an ihype lipidemic,
an ioxidan , an i umo ,
an ihype glycemic, and
an i-neu odegene a i e,
ca diop o ec i e
[59,154,155,159,
161]
Galloca echin C15H14O70.07–0.95 inhibi o o melanin
biosyn hesis [45,59,162]
Epica echin C15H14O60.06–1.9 an ioxidan [71,161]
Epica echin Galla e C22H18O10 0.3–0.9 an ioxidan [161]
Ca echin C15H14O60.095–7.7 an ioxidan , an icance ,
ca diop o ec i e, an i ungal [45,59,71,161,162]
Vanillic Acid C8H8O40.02–0.07 neu op o ec i e,
an i-in lamma o y [45,59,158]
Ca eic Acid C9H8O40.03–0.2
an ioxidan , pho op o ec i e
[45,59,163]
Rosmani ic Acid C18H16O80.4–0.8 an ioxidan , an idiabe ic,
an ibac e ial, an i i al [59,164,165]
Ca echin Galla e C22H18O10 0.002–1.5 an ioxidan , an icance [71,166]
Taxi olin C15H12O70.01–4.7 an ioxidan , an icance ,
an i-in lamma o y [45,59,148,167]
3,4 Dihyd oxy-Benzoic
Acid C9H10O40.08–0.8
neu op o ec i e, an ioxidan ,
nema icidal ac i i y [45,59,168]
Ellagic acid C14H6O80.4–4.0 an i-in lamma o y,
an ioxidan [45,59,169]
Na ingin C27H32O17 0.8–2.0 no ound [45,59]
Apigenin C15H10O50.3–0.5 an icance , an ioxidan ,
an i-in lamma o y [45,59,170]
Res e a ol C14H12O30.03–0.4
an ioxidan , an i-cance ,
ca diop o ec i e,
an i-in lamma o y
[45,59,159,171]
Fe ulic acid C10H10O40.06–0.5
an ioxidan , pho op o ec i e
[45,59,163]
p-couma ic acid C9H8O3n.q.
an ioxidan ,
an i-in lamma o y,
hepa op o ec i e and
enop o ec i e,
an i-neu odegene a i e,
an i-choles e olemic,
imp o e insulin esis ance,
an i- y osinase,
an imic obial
[59,154–156]
Molecules 2020,25, 2931 18 o 29
Table 3. Con .
Name Chemical
Fo mula
Concen a ion
Range (mg/g) Bioac i i ies Re e ence
Que ce in C15H10O70.06–1.1 in lamma o y, an imic obial,
an icance [45,59]
P ocyanidin A2 C30H24O12 n.q. an ioxidan [148]
P ocyanidin B1 C30H26O12 n.q.
an ioxidan , neu op o ec i e,
an i-p oli e a i e ac i i y [148]
P ocyanidin B2 C30H26O12 n.q.
an ioxidan ,
an i-in lamma o y,
ca diop o ec i e,
neu op o ec i e,
an i-p oli e a i e ac i i y
[148]
n.q.–no quan i ied.
As one can see om Table 3, he main polyphenol compounds ound in ex ac s om pine needles
a e p-couma ic acid and epica echin, in pine seeds e iodic yol and axi olin, and in pine ba k ca echin,
gallic acid, and axi olin. In he ollowing ex , we summa ize he bioac i i ies o he indi idual
compound ound in he ex ac s o pine species. Howe e , we wan o d aw he a en ion o he eade
o he idea ha , in e ms o exp essing biological ac i i ies, he polyphenols ac as g oup o compounds
a he han indi idual compounds, and syne gis ic and/o an agonis o simply di e en e ec s may
be ound.
The p-couma ic acid oge he wi h e ulic and ca eic acids a e he mos common hyd oxycinnamic
acids in pine-based ex ac s. The hyd oxyla ion o p-couma ic acid esul s in he o ma ion o e ulic
acid, while he oxyme hyla ion o p-couma ic acid p oduces ca eic acid, espec i ely. These phenolic
acids a e used as p ecu so s in he syn hesis o lignins and o he phenolics [
136
]. Tao iq e al. [
156
]
conduc ed a s udy on indi idual compounds as possible ing edien s in cosmeceu ical o mula ions.
The au ho s concluded ha p-couma ic, p o oca echuic, and cinnamic acids displayed an i- y osinase,
an imic obial, and an i-in lamma o y ac i i ies, showing hei po en ial o he cosmeceu ical indus y.
Ca eic acid and, a a highe deg ee, e ulic acid p o ed o p o ec he skin agains UVB-induced
e y hema. Besides as an ioxidan s, hese wo hyd oxycinnamic acids can be used as pho op o ec o s in
skin cosme ics [163].
The p o oca echuic, anillic, and sy ingic acids a e he h ee commonly ound hyd oxybenzoic
acids [
136
]. This ee hyd oxybenzoic acids we e also ound in pine ex ac s (Table 3). Vanillic acid
demons a ed an i-in lamma o y ac i i y wi h neu op o ec i e ac i i y and was ound o be a p omising
candida e o p e en ing and/o delaying he onse and p og ession o ischemic inju y and ascula
demen ia [
158
]. In o he cases, he use o a mix u e o phenolic compounds a he han he indi idual
compounds exhibi s s onge ac i i ies. Fo example, he combined use o sy ingic acid, es e a ol, and
gallic acid, in a s, e ealed an ioxidan and ca diop o ec i e ac i i ies [
159
]. Res e a ol also showed
an an icance e ec when examined in lung, p os a e, b eas , skin, and gas oin es inal cance s [
172
].
Res e a ol is he mos known cons i uen o wines and g apes, bu i was also ound in pine ba k
ex ac s (Table 3). I was also p o en ha es e a ol has an i-in lamma o y capaci y, especially in
he skele al muscle, bu i is less ac i e in li e [
171
]. Mo eo e , gallic and p-couma ic acids we e
conside ed as p omising adju an agen s agains he p og ession o neu odegene a ion in he b ain
by diabe es [
155
]. Rosma inic acid is known o ha e a numbe o po en ially bene icial biological
e ec s and is an acid es e o ca eic acid and 3(3,4-dihyd oxyphenyl)lac ic acid. The use o osma inic
acid in gela in edible ilm showed long- e m an ibac e ial ac i i y. Rosma inic acid edible ilms may
ha e p omising applica ion in he ields o ood and pha maceu ical packaging, as hey showed
a good an ibac e ial ac i i y e en a e 3 mon hs o s o age [
173
]. Rosma inic acid was ound in
ex ac s o pine ba k in concen a ions be ween 0.4 and 0.8 mg/g [
59
]. This acid was ound o be he
p edominan compound o Sal ia species. S ong co ela ions be ween he osma inic acid con en s
and bioac i i es o Sal ia samples we e es ablished [
165
]. Mo eo e , his acid demons a ed po en
an i i al p ope ies [
164
]. 3,4 dihyd oxybenzoic acid is uni e sal in he Angiospe m plan s, as i
Molecules 2020,25, 2931 19 o 29
is cons i uen o lignin. I is a s ong an ioxidan , as well as a neu op o ec i e agains A
β
-induced
neu onal damage [
168
]. This acid can be used in o mula ions o phy onema ode con ol, as i showed
nema icidal ac i i y agains ju eniles o M. incogni a [174].
As we can see om he Table 3, in di e en pine ex ac s, many ca echin compounds wi h
diphenylp opane (C
6
–C
3
–C
6
–) skele ons we e ound. Epigalloca echin, epigalloca echin galla e, and
epica echin a e he main cons i uen s o he lea es o Camellia sinensis ( he ea plan ), while ca echin
galla e is a mino polyphenolic cons i uen in g een ea: 1.28% (by weigh ) o he o al ca echin
con en in g een ea [
166
]. These ca echins a e esponsible o he as ingen and bi e as e o he
g een ea [
153
]. Ca echin is he main phenolic compound p esen in P.pinas e ba k ex ac ollowed
by epica echin and epica echin galla e [
161
]. Galloca echin was ound also in No way sp uce and
con i med o be a s ong inhibi o o melanin biosyn hesis; howe e , he e is li le in o ma ion on he
biological ac i i ies o his compound [
162
]. All hese ca echins ha e s ong an ioxidan s and an icance
ac i i ies agains di e en ypes o cance [
166
]. Ca echins ha e ecei ed conside able a en ion as
p omising candida es o de elopmen o he apeu ic agen s.
Taxi olin, as an indi idual compound, is ex ensi ely s udied. I was ound in he pine ex ac s
o seeds and ba k; in ba k, i is p esen in much highe concen a ions han in seeds [
45
,
59
,
157
].
Fo ins ance, his compound was eco e ed om P.nig a ba k [
120
] wi h a maximum ex ac ion
eco e y o 34%. Taxi olin was de ec ed as he majo compound in o he needle lea ed ees such
as he Japanese la ch, La ix kaemp e i [
175
]. I s main bioac i i ies a e an ioxidan , an icance , and
an i-in lamma o y [
148
,
167
]. Que ce in is a axi olin- ela ed la onoid ound in onions, and i showed
an i-in lamma o y, an imic obial, and an icance p ope ies (
in i o
and
in i o
) [
176
]. Que ce in- ich
ex ac s om onion skin can be used in unc ional b ead p oduc ion [176].
Acco ding o Lan o and co-wo ke s [
157
], e iodic yol was one o he main compounds ound
in ex ac s o Sibe ian pine ba k. E iodic yol, as axi olin, can be ind in ci us ui s. I has showed
an ioxidan and an i-in lamma o y ac i i ies. Recen indings indica ed ha e iodic yol migh be a new
p e en a i e agen o ps eoa h i is [
177
]. Ano he p omising he apeu ic agen o he ea men
o os eoa h i is is ellagic acid [
169
]. I is ound in high concen a ions in he e hanolic ex ac s o
P. pinas e [59], which is also a cons i uen in he ui peel o be ies and nu s [169].
Apigenin is ound abundan ly in he bs, ui s, and ege ables (peppe min , g ape ui , pa sley).
I has po en an ioxidan , an i-in lamma o y, and an icance p ope ies [
170
]. Gascon e al. [
148
] ound
h ee p ocyanidin compounds in pine ba k ex ac s: A2, B1, and B2. The ac i i ies o p ocyanidins
depend on hei s uc u e, especially on hei deg ee o polyme iza ion. P ocyanidin B2 is one o
he mos ac i e molecules wi hin he p ocyanidins, as well as he mos s udied. I is also ound in
cocoa and g ape seeds. The h ee compounds ha e an ioxidan ac i i y; B- ype p ocyanidins ha e also
neu op o ec i e ac i i y. The iches se o bioac i i ies agglome a es o he p ocyanidins B2, bu as
we men ioned, his is also he mos s udied one.
The e a e se e al pine ba k comme cial ex ac s: Oligopin
®
, Pycnogenol
®
, and Fla angenol
®
.
Pycnogenol
®
is he mos known and mos s udied one. I s ex ac ion in ol es s anda dized consecu i e
s eps using wa e and e hanol as sol en s. I is a polyphenol- ich ex ac p epa ed om P. pinas e
(F ench ma i ime pine). The main cons i uen s a e p ocyanidins (85%), la onoids (ca echin, axi olin),
as well as some phenolic acids in mino amoun s (gallic, ca eic, and e ulic acid) [
149
]. This ex ac
p o ed o ha e excellen an ioxidan p ope ies ha can p omo e a ious heal h p ope ies such as
ca diop o ec i e, an icance , an ihype ensi e, and an i-in lamma o y [
118
,
150
]. In ano he s udy,
he clinical e iciency o Pycnogenol
®
in he managemen , ea men , and con ol o ch onic enous
insu iciency and enous mic oangiopa hy was p o en [
178
]. This ex ac showed also an i-diabe ic
p ope y, as he supplemen a ion o Pycnogenol
®
o con en ional diabe es ea men lowe ed glucose
le els and imp o ed endo helial unc ion [
179
]. Oligopin
®
is ano he ex ac ob ained om he pine
ee P. pinas e om a speci ic loca ion in F ance (Landes o Gascony). I s p oduc ion includes wo
ex ac ion s eps and one pu i ica ion s ep. This me hodology ensu e ha he ob ained ex ac has
Molecules 2020,25, 2931 20 o 29
a speci ic and cons an composi ion. The main compounds ound in Oligopin
®
a e la onoids (ca echin
and axi olin) and acids ( e ulic, gallic, ca eic, p-couma ic, and p o oca echic) [180].
As a inal ema k, he indi idual polyphenol compounds ound in he ex ac s o pine ba k
ha e di e se bioac i i ies ha align wi h he men ioned p e iously bioac i i ies o he hole ex ac s
such as an ioxidan , an icance , ca diop o ec i e, an idiabe ic, an i-in lamma o y, e c. Pine ex ac s
ha e ac i e ing edien s ha a e use ul o he ood indus y as supplemen s o na u al pigmen s, o
ood p ese a ion and as ac i e ood packaging. In he cosme ic o mula ions, hey can be used o
p o ec ing he skin agains oxygen eac i e species, o med by pollu ion, s ess, o ul a iole eac ion.
6. Conclusions and Fu u e Pe spec i es
Pine esidues and by-p oduc s a e an impo an sou ce o biocompounds wi h high indus ial
in e es . They can be eco e ed using he bio e ine y concep , hus con ibu ing o he ci cula economy.
Mo e en i onmen ally iendly echniques ha e been explo ed o a oid he la ge amoun s o
(o ganic) sol en s, ene gy consump ion, and was e gene a ion ypical o con en ional sol en ex ac ion
p ocesses. Al hough eplacing con en ional echnologies by non-con en ional ones has eme ged,
imp o emen s a e necessa y in e ms o deep knowledge o he ex ac ion p ocesses and scaling up.
UAE, MAE, SFE, PLE, and OH a e some o hese eme ging p omising echnologies o bioac i e
compounds ex ac ion in alignmen wi h he G een Chemis y p inciples. Rega ding he ex ac ion
s ep, he selec ion o he mos app op ia e echniques di e s acco ding o he ype o compounds
a ge ed o eco e y and inal aimed unc ionali y/applica ion. Howe e , he e is no a uni e sal
ex ac ion me hod sui able o he ex ac ion o all pine phenolics. The di e en pine species ha e
di e en indi idual phenolic composi ion. Fo example, he main phenolic compound ound in
ex ac s o Po uguese pine is he axi olin, whe eas i was no ound in Macedonian pine species.
Depending on he inal pu pose o he ex ac ion, an indi idual s udy mus be ca ied on o une he
bes ex ac ion p ocedu e.
In e es ingly, all ex ac s om pine, ega dless he sol en , he me hod, pine species, and he plan
pa used, ha e high amoun s o polyphenols.
Howe e , he e a e di e ences in he concen a ions and ype o he indi idual compounds as
well as in he s eng h o he bioac i i ies. The e a e no many s udies showing iden i ica ion and e en
less s udies showing quan i ica ion o he indi idual polyphenols in ex ac s om pine species.
Pine ex ac s ha e a numbe o desc ibed bioac i i ies ha may be bene icial o he human
heal h. As a consequence, pine ex ac s ha e high po en ial as cons i uen s in o mula ion o he ood,
cosmeceu ical, and pha maceu ical indus ies.
The possible eu iliza ion o he pine esidues is ye limi ed, compa ed o i s po en ial. In his
con ex , mo e s udies a e needed o ind and de elop new p oduc s and uses esul ing om pine
esidues and by-p oduc s.
Funding:
Thiswo kwas undedby hePo ugueseFounda ion o ScienceandTechnology(FCT)unde hescopeo
he s a egic unding o UIDB/04469/2020 uni and BioTecNo e ope a ion (NORTE-01-0145-FEDER-000004) unded
by he Eu opean Regional De elopmen Fund unde he scope o No e2020 - P og ama Ope acional Regional do
No e and by p og am INTERREG V-B Sudoe (REDVALUE, SOE1/P1/E0123). Zla ina Genishe a is suppo ed by he
p ojec OH2O (POCI-01-0145-FEDER-029145) unded by FCT and Fundo Eu opeu de Desen ol imen o Regional
(FEDER) unde he scope o P og ama Ope acional de Compe i idade e In e nacionalizaçao (POCI)-COMPETE
2020 and Po ugal 2020. Elisa Zanuso is ecipien o a PhD ellowship suppo ed by he Mexican Science and
Technology Council (CONACYT ID 639021/495314). Ped o San os is ecipien o a PhD ellowship suppo ed by
a doc o al ad anced aining (call NORTE-69-2015-15), unded by he Eu opean Social Fund unde he scope o
No e2020 - P og ama Ope acional Regional do No e (NORTE-08-5369-FSE-000036).
Con lic s o In e es : The au ho s decla e no con lic o in e es .
Molecules 2020,25, 2931 21 o 29
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