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Food Chemistry: X 12 (2021) 100133
Available online 25 September 2021
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Recent advances and trends in extraction techniques to recover polyphenols
compounds from apple by-products
Laise C. da Silva
a
, Juliane Vigan´
o
a
, Leonardo M. de Souza Mesquita
a
, Arthur L. Bai˜
ao Dias
b
,
Mariana C. de Souza
a
, Vitor L. Sanches
a
, Jaisa O. Chaves
a
, Rodrigo S. Pizani
a
,
Leticia S. Contieri
a
, Mauricio A. Rostagno
a
,
*
a
Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences (FCA), University of Campinas (UNICAMP), Rua Pedro Zaccaria 1300,
13484-350 Limeira, SP, Brazil
b
Laboratory of High Pressure in Food Engineering, School of Food Engineering (FEA), University of Campinas (UNICAMP), Rua Monteiro Lobato 80, 13083-862
Campinas, SP, Brazil
ARTICLE INFO
Keyword:
Apple pomace
Malus sp.
Phenolics compounds
Bioactive compounds
Conventional extraction
Non-conventional extraction
ABSTRACT
Apple is one of the most consumed fruits worldwide and has recognized nutritional properties. Besides being
consumed fresh, it is the raw material for several food products, whose production chain generates a considerable
amount of by-products that currently have an underestimated use. These by-products are a rich source of
chemical compounds with several potential applications. Therefore, new ambitious platforms focused on reusing
are needed, targeting a process chain that achieves well-dened products and mitigates waste generation. This
review covers an essential part of the apple by-products reuse chain. The apple composition regarding phenolic
compounds subclasses is addressed and related to biological activities. The extraction processes to recover apple
biocompounds have been revised, and an up-to-date overview of the scientic literature on conventional and
emerging extraction techniques adopted over the past decade is reported. Finally, gaps and future trends related
to the management of apple by-products are critically presented.
1. Introduction
Apples (Malus sp.) are among the most popular fruits consumed
worldwide and are a rich source of valuable chemical compounds (e.g.,
polyphenols, pectin, and bers) in the human diet. Bioactive compounds
such as polyphenols are naturally produced by a plant or induced by
physical or chemical stresses. Generally, polyphenols act as regulators of
growth factors and secondary antioxidant defense in different vegetable
tissues. These compounds act as antioxidants and anti-inammatory
agents for human health, playing an important role in preventing (or
treat) non-communicable chronic diseases (Kumar & Pandey, 2013;
Ponte et al., 2021).
Due to the wide variety of phenolic compounds and potential bio-
logical properties, the investigation of apple and apple by-products is a
boundless eld, notably focusing on a better understanding of the main
bioactive compounds, the most appropriate extraction methods, puri-
cation techniques, and renement of the nal product and its biological
applications and analysis methods. Thus, this review aims to ll part of
this gap by gathering studies from the past two decades dealing with
phenolic extraction from apple and apple by-products through conven-
tional and non-conventional techniques. The primary fruit compounds
are comprehensively summarized, and the future trends and perspec-
tives for apple by-product extraction are provided.
2. Apple and its main bioactive compounds
>60 phenolic compounds are currently identied in apple fruit. They
are part of plants’ secondary metabolism, performing essential roles,
such as growth, defense mechanisms against pathogens, coloring, and
aroma properties. Moreover, they are vital to growth and reproduction
and are synthesized mainly when the plant is submitted to stressful
conditions, such as infections, wounds, and ultra-violet radiation
(Haminiuk et al., 2012; Hyson, 2011).
Phenolic compounds have one or more aromatic rings in their mo-
lecular structures with one or more hydroxyl groups, which are related
to the human body’s antioxidant properties, i.e., they react with free
radicals forming stable radicals (Fu et al., 2011). The antioxidant
properties promote biological benets such as anti-cancer,
* Corresponding author.
Contents lists available at ScienceDirect
Food Chemistry: X
journal homepage: www.sciencedirect.com/journal/food-chemistry-x
https://doi.org/10.1016/j.fochx.2021.100133
Received 14 July 2021; Received in revised form 3 September 2021; Accepted 22 September 2021
Food Chemistry: X 12 (2021) 100133
2
antimicrobial, and cardiovascular protection (Carocho & Ferreira,
2013), among others.
Table 1 presents an overview of the main classes, subclasses, and
health benets of phenolic compounds from the apple, which can be
classied into non-avonoids or avonoids. Among the non-avonoids,
phenolic acids are subdivided into hydroxycinnamic and hydrox-
ybenzoic. The quinic and caffeic acids have been the most identied
compounds in different apple cultivars, reaching between 4 and 18% of
Table 1
An overview of the main classes, subclasses, and health benets of the major phenolic compounds identied in apples.
Classes Subclasses Compounds Benets associated References
Acids Hydroxycinnamic Chlorogenic; Cryptochlorogenic Antiobesity, antihypertensive and
neuroprotective
Naveed et al.
(2018)
Caffeic; 4-Caffeoylquinic; 5-Caffeoylquinic Aid against injury to ischemia–reperfusion Sato et al. (2011)
p-coumaric; 5-p-Coumaroylquinic; p-coumaric acid-O-hexoside; 4-O-p-
coumaroylquinic; p-coumaroylquinic
Lung anticancer, analgesic and mitigating
effects in diabetes
Pei et al. (2016)
Ferulic Vasodilator, antidiabetic and
anticarcinogenic action in gastrointestinal
tumors
Kumar & Pruthi
(2014)
Sinapic acid-O-glucoside Antidiabetic, aid against
neurodegeneration and anxiety
Chen (2016)
Hydroxybenzoic Syringic Cardiovascular diseases, cerebral ischemia
and liver anticancer
Srinivasulu et al.
(2018)
Gentisic Antioxidant and anti-inammatory Zhou et al.
(2017)
Protocatechuic Antiobesity and antihyperglycemic D’Archivio et al.
(2014)
Salicylic Anti-inammatory and chemoprotective
properties
Dachineni et al.
(2016)
Ascorbic Antitumor, antiviral, antioxidant Macan et al.
(2019)
Vanillic Antioxidant, anti-inammatory, and
neuroprotective effects
Ullah et al.
(2020)
Flavonoids Flavonols Quercetin; Quercetin-3-O-diglucoside; Quercetin-3-O-galactoside;
Quercetin-3-O-glucoside; Quercetin-3-O-rhamnoside; Quercetin-3-O-
rutinoside; Quercetin-3-O-xylanoside; Quercetin-O-xylosyl-pentoside
Anti-inammatory and antioxidant Lesjak et al.
(2018)
Rhamnetin; Rhamnetin-3-O-glucoside Antiviral Ferenczyova
et al. (2020)
Isorhamnetin-3-O-galactoside, isorhamnetin-3-O-glucoside, isorhamnetin-3-
O-rutinoside, isorhamnetin-3-O-rhamnoside
Antihypertensive, aid against
cardiovascular diseases
Eisvand et al.
(2020)
Kaempferol-O-glucoside Breast, prostate and colon anticancer
properties
Wang et al.
(2019)
Rutin Antitumor, antimicrobial, anti-
inammatory, and neuroprotector
Budzynska et al.
(2017)
Reynoutrin Antithrombotic, anticancer, and
antidiabetic
Li et al. (2016)
Avicularin Anti-allergic and aid against gastric cancer
development
Guo et al. (2018)
Quercitrin Neuropharmacological actions, anti-viral
and anticancer
Zhi et al. (2016)
Flavones Apigenin Antidiabetic, aid against amnesia,
Alzheimer’s disease, depression and
insomnia
Salehi et al.
(2019)
Chrysoeriol Inhibit the activity of pancreatic lipase Ramirez et al.
(2016)
Luteolin; Luteolin-7-O-galactoside; Luteolin-7-O-glucoside Anti-inammation, anti-allergy, and
pancreatic anticancer
Imran et al.
(2019)
Flavanones Hesperidin-O-pentoside Neuroprotection Hajialyani et al.
(2019)
Eriodictyol; Eriodictyol-hexoside Aid to Insulin secretion Hameed et al.
(2018)
Naringenin-7-O-glucoside; Naringenin-7-O-neohesperidoside; Naringenin-7-
O-rutinoside; Naringenin-O-glucuronide.
Immunomodulatory agent,
neuroprotective and anti-atherosclerotic
properties
Hartogh & Tsiani
(2019)
Flavanols (−)-Epicatechin; (−)-Epigallocatechin 3-gallate; (−)-Epigallocatechin;
(−)-Epigallocatechin 3-gallate
Potential in the treatment and diabetes and
cardiac pathology
Shay et al.
(2015)
(+) Catechin Prevention of hypertension and high blood
cholesterol, Stomach anticancer
Matsui (2015)
Procyanidin B1; Procyanidin B2; Procyanidin B3; Procyanidin B5
Procyanidin C1
Esophagus anticancer Connor et al.
(2014)
Anthocyanins Cyanidin 3-O-galactoside; Cyanidin 3-O-arabinoside; Cyanidin-7-
arabinoside; Cyanidin 3-O-xyloside
Anti-inammation and aid to decrease
cholesterol levels
Ding et al. (2006)
Peonidin Antioxidant, anticancer and antidiabetic Rajan et al.
(2018)
Dihydrochalcones Phloretin; 3-Hydroxyphloretin 2′-O-glucoside; Phloretin 2′-O-xylosyl-
glucoside
Antimicrobial Barreca et al.
(2014)
Phloridzin; 3-hydroxyphloridzin Antihyperglycemic
Makarova et al.
(2014)
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
3
total polyphenols in the fruit. In addition, 5-caffeoylquinic or chloro-
genic acid, p-coumaroylquinic, and p-coumaric acids have also been
reported. Both hydroxycinnamic and hydroxybenzoic acids can be found
in higher amounts conjugated to components of cell walls, such as cel-
lulose or lignin, or even forming protein complexes that can be bounded
to sugar or organic acids (Barros et al., 2009).
Flavonoid groups in apples can be subdivided into avonols
(71–90%), avan-3-ols (1–11%), dihydrochalcones (2–6%), and antho-
cyanins (1–3%). Catechins, epicatechins, and procyanidin B2 are the
main avan-3-ols in apples’ skin and pulp. The subgroup of avanols is
usually found in different quercetin glycosides, with quercetin 3-glyco-
side as the leading representative (Bondonno et al., 2017; Hyson,
2011). From the anthocyanins group, cyanidin 3-galactoside is the most
representative in the red apples’ skin since it is responsible for the red
color of the apples. Dihydrochalcones, such as phloridzin and phloretin,
are associated with the fruit sugar content, such as glucose and xylo-
glucan. Dihydrochalcones are found predominantly in apple seeds and
stems, typical compounds of the industrial by-product of the fruit (Da
Silva et al., 2020; Jakobek & Barron, 2016).
Different apple species, cultivar characteristics, maturation degree,
storage conditions, among others, are the main factors that determine
the phenolic concentration in the fruit (Jakobek & Barron, 2016).
Exposure to ultraviolet radiation, predators, and soil diversities, for
example, make the fruit skin more concentrated in phenolics than other
parts, such as pulp and seeds.
In general, the dry basis concentration of phenolics may be higher in
fresh fruit than in pomace as the latter comes from industrial processing
(press, thermal processes for drying, exposure to light, among others). In
addition, pomace results from the mixing of all parts of the fruit and,
therefore, its chemical composition is a consequence of this mixture and
the treatment that the by-product has undergone. For example, the
avonoids are predominant in the skin, while higher phenolic acids
amount is found in the pulp and dihydrochalcones, hydroxycinnamic
acids, avan-3-ols, proanthocyanin B2 and avonols are present in the
seeds. The pomace can, but not necessarily must consist of these
phenolic compounds. Fruit by-products are complex matrices that pre-
sent trends and not rules about their composition as they may have
undergone different industrial processes that impact their nal state.
Nevertheless, the most signicant compounds in the apple pomaces
are chlorogenic acid, caffeic acid, (+)-catechin, (−)-epicatechin, rutin,
quercetin glycosides, and phlorizin. As shown in Table 1, such com-
pounds display several biological activities, allowing opportunities to
design new products, especially from their extracts. Therefore, extrac-
tion congures an essential step in the reuse chain of by-products.
It is worth mentioning that apple seeds may contain other com-
pounds such as amygdalin and cyanogenic diglucoside. Cyanide toxicity
in humans occurs at doses between 0.5 and 3.5 mg/kg body weight.
However, this compound is present in apple seeds between 0.06 and 0.2
mg cyanide equivalent/g of apple seeds (Bolarinwa et al., 2015; Lu &
Foo, 1998), depending on the cultivation. (Xu et al., 2016). Even so,
attention should be paid to extraction products from the pomace con-
taining seeds to monitor these compounds’ concentration.
3. Extraction of bioactive compounds
Several techniques have already been employed to extract bioactive
compounds from apples-based raw materials in laboratory scales. Whole
apple and apple by-products are similar matrices regarding the
composition of the phenolic compounds and, therefore, the selection of
the method for the extraction of them depends more on the character-
istics of the methods than on the matrix. The extraction processes are
commonly classied as conventional and modern extraction methods.
Both have been used to recover compounds from apple-based matrices,
which are the focus of this section, providing practical and theoretical
characteristics and giving perspectives on the direction of this topic in
future years.
The classical or conventional extraction methods have been used for
at least ten years to obtain compounds from apple-based matrices;
maceration, Soxhlet, mild homogenization, and magnetic stirring are
the main examples. Maceration and Soxhlet have been less employed
than mild homogenization and magnetic stirring, and two rst have
mainly been used by published papers for comparison or validation of
alternative extraction techniques, or even to evaluate some initial
extraction parameters like the mass ratio between solvent and sample
(Azmir et al., 2013; Ferrentino et al., 2018; Moreira et al., 2017). Con-
ventional methods are of easy operation at lab scale; however, they
present some drawbacks like the lack of ne temperature control, light
exposure, and longer extraction time, which may reduce the extraction
yields and the extract concentration of target compounds (Azmir et al.,
2013; Mustafa & Turner, 2011). Additionally, for a long time, they
employed extraction solvents that nowadays are avoided due to envi-
ronmental and safety issues. Thanks to concerns and warnings released
by the scientic community, such dangerous solvents have been avoided
and replaced by solvents Generally Recognized as Safe (GRAS).
Some of the mentioned conventional extraction techniques, such as
Soxhlet and magnetic stirrer, have been applied to apple-based raw
materials mainly as preparative methods for lab-scale analytical pur-
poses. Additionally, conventional extractions for process engineering
purposes often stumble on scaling up limitations, which corroborates the
search for innovative and scalable extraction technologies.
Moreover, scalability is a critical point that needs to be evaluated in
new proposals. Unfortunately, most of the published works dealing with
laboratory scales do not address discussions about how feasible the
method is at large scales. Furthermore, to the best of our knowledge, the
possibility of scaling-up is a pivotal point to cross de boundary between
research laboratories and industry.
Modern or non-conventional methods have emerged in the last years
to overcome the mentioned downsides. In addition, to receive the seal of
green extraction or green techniques, they present some advantages over
the conventional processes due to the lower energy and solvent con-
sumption, shorter extraction time, and well-dened parameters that
result in better extraction performance (higher yields and extract con-
centration). The ultrasound-assisted extraction (UAE), microwave-
assisted extraction (MAE), pressurized-liquid extraction (PLE), and su-
percritical uid extraction (SFE) are examples of non-conventional
techniques to recover phenolic compounds from vegetable matrices.
These methods have been employed to extract apple bioactive com-
pounds in the past few years. Usually, the studies propose to nd the best
operational conditions (e.g., type of solvent, temperature, time, pres-
sure, power) to obtain phenolics from this fruit (Armenta et al., 2019;
Azmir et al., 2013; Pingret et al., 2012; Santos et al., 2019; Da Silva et al.,
2020; Souza et al., 2020; Sumere et al., 2018; Xu et al., 2017). Never-
theless, except for SFE that is already well established in industrial
scales, the other methods are starting to gain ground in the industry and
therefore still need adjustments for larger scales.
3.1. Conventional extraction techniques
Most of the studies found in the past decade literature dealing with
apple compounds obtention through conventional extraction are based
on the extraction power of different solvents, temperature, extraction
time, and solid to liquid ratio (SLR: sample mass (g)/solvent volume
(mL)) (Fromm et al., 2013; Hern´
andez-Carranza et al., 2016; Reis et al.,
2012). Table 2 presents works that applied conventional techniques to
extract phenolics from apple and apple by-products, including the
operational parameters and analyzed most important compounds. Fer-
rentino et al. (2018) used the Soxhlet apparatus to obtain phenolics from
apple pomace using ethanol as the solvent for six hours. Rana et al.
(2015) used homogenization to study the effects of different solvents on
the extraction of phenolic compounds from apple pomace. The authors
observed that acetone was the best solvent to recover phenolic com-
pounds. Mild homogenization was also used to extract phenolics from
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
4
apple tree wood (Moreira et al., 2017), applying ethanol as the solvent.
Some important compounds of the fruit are mainly nonpolar. Thus,
organic solvents or their mixtures give the highest yield in conventional
extractions.
It is important to highlight those other parameters, such as temper-
ature and extraction cycles, that also affect the target compounds yield.
Pure water appears as a green and low-cost alternative solvent; however,
it is necessary to increase the temperature or the number of extraction
cycles to assure higher yields (Fromm et al., 2013; Hern´
andez-Carranza
et al., 2016). Reis et al. (2012), for example, used pure water, acetone
(20–100%, v/v), and methanol (20–100%, v/v) to extract phenolics
from apple pomace. Three extraction cycles were used for pure water,
while only one extraction cycle was enough for acetone and methanol to
achieve equivalent yields. The authors noticed that all solvents could
extract phenolics, but pure water extracted less of the target compounds
due to the polarity and compatibility. Water also led to a lower selec-
tivity, promoting the extraction of other components and reducing the
relative purity of the extracts. Methanol (70–99.9%, v/v) and acetone
(50–80%, v/v) were compared in a study conducted by Alberti et al.
(2014) to extract chlorogenic acid and phloridzin from apple by mild
homogenization. The authors observed that the best operational con-
dition for methanol was 84.5% (v/v) for 15 min at 28 ◦C, and acetone at
65% (v/v) for 20 min at 10 ◦C. Corroborating this nding, Rezaei et al.
(2013) showed that extractions performed with methanol recovered
higher yields of phenolics than those performed with ethanol, using both
the Soxhlet (221 mg tannic acid equivalent (TAE)/g dry matter (d.m.))
and maceration (148 mg TAE/g d.m.) techniques. The methanol and
acetone’s ability to extract phenolic compounds from plant sources is
well established. Although both solvents are acceptable for analytical
purposes, substitutes (GRAS) are very welcome, especially when
applying the extract for human consumption, besides all the environ-
mental impact inherent in producing these solvents. Moreover, safer
substitutes should be applied to replace these organic solvents, such as
non-volatile alternative solvents, namely, ionic liquids (ILs), eutectic
solvents, and surfactants.
Besides the most appropriate solvent, the particle size is another
determinant physical parameter that must be evaluated to guarantee a
successful extraction, especially on conventional extraction techniques.
The smaller particle size seems for high-performance extraction of
bioactive compounds, which promotes better mass transfer, and conse-
quently, the higher release of the bioactive compounds in the extraction
solution in a shorter extraction time. The sample preparation steps, e.g.,
drying or packaging, also may affect the extraction yield and the extract
concentration since factors like oxidation of the components induced by
light or oxygen can occur during the raw material pretreatment. The
drying procedures’ inuence on the extraction yield was studied Rana
et al. (2015), using quercetin, phloridzin, and phloretin from apple
pomace as target compounds. The authors showed that higher phenolics
content was found in freeze-dried samples, followed by those dried in an
oven and dried under the sun. Although, in general, drying at high
temperatures and air circulation is harmful to the maintenance of
phenolic compounds, attention must be paid to raw materials with a
Table 2
Summary of publications using conventional extraction techniques for recovery phenolic compounds from apple, and their respective operational extraction conditions
(solvent, temperature, time, and SLR), the most important compounds analyzed, and the best conditions reported.
Technique Sample Solvent
(%, v/v)
Temperature
(◦C)
Time
(min)
SLR
(g/
mL)
Most important compounds analyzed Yield of
extraction
(TPC)
Best conditions
reported
References
HMG Whole
Apples
ACT
50–80
MEOH
70–99.9
10–40 10–20 0.017 Chlorogenic Acid and Phloridzin 5.90 mg/g 84.5% MEOH,
15 min, 28 ◦C or
65% ACT, 20
min, 10 ◦C
Alberti et al.
(2014)
HMG Apple
pomace
ACT 50
ETOH 50
MEOH
50
30 60 0.05 Quercetin, Phloridzin and Phloretin 3.31 mg/g 50% ACT, 60
min, 30 ◦C
Rana et al.
(2015)
HMG Apple
pomace
Water
MEOH
20–100
ACT
20–100
RT 90 0.075 Hydroxycinnamic Acids, Flavonols,
Flavanols, Dihydrochalcones, and
Flavones
n.i. Water, 40%
MEOH, 40%,
ACT, RT, 90 min
Reis et al.
(2012)
HMG Apple
tree
wood
ETOH
20–80
20–55 180–1140 0.025 Phenolics Acids, and Phloridzin 43.2 mg/g 50% ETOH,
55 ◦C, 120 min
Moreira et al.
(2017)
Mag- str Apple
seeds
ACT
60–70
0–42 60–1440 1.25 Hydroxybenzoic Acid, Flavan-3-ols, and
Dihydrochalcone
2.99 mg/g 60–70% ACT,
25 ◦C, 60 min
Fromm et al.
(2013)
Mag-str Apple
pomace
Water
ETOH
50–100
MEOH
50–100
60 30 0.04 Gallic Acid/Protocatechuic Acid
Glucoside, Chlorogenic Acid,
Epicatechin, Rutin, Hyperoside,
Quercetin Derivatives, Quercetin
Rhamnoside, Phloretin Xylosyl
Glucoside, Phlorizin
– 80% MEOH, 50%
ETOH, 60 ◦C, 30
min
Da Silva et al.
(2020)
Mag-str Apple
pomace
Water 20–60 30–720 0.004 Quercetin, Epicatechin, Chlorogenic
Acid, Procyanidin B2, and Phloretin
6.89 mg/g Water, 60 ◦C,
720 min
Hern´
andez-
Carranza et al.
(2016)
MCT Apple
pomace
ETOH RT 60 0.05 Gallic Acid, Chlorogenic Acid, Catechin,
Rutin and Phloridzin
n.i. – Grigoras et al.
(2013)
MCT Apple
pomace
ETOH
MEOH
RT 1440 0.1 n.i. 148 mg/g MEOH, 1440
min, RT, 0.1 SLR
Rezaei et al.
(2013)
MCT Apple
pomace
Water 100 37 0.016 Phlorizin, Epicatechin, Quercetin, and
Phloretin
2.41 mg/g – Ferrentino
et al. (2018)
SX Apple
pomace
ETOH
MEOH
RT 60–240 n.i. n.i. 221 mg/g MEOH, 180 min,
RT
Rezaei et al.
(2013)
SX Appel
pomace
ETOH RT 360 0.033 Phlorizin, Epicatechin, Quercetin, and
Phloretin
4.13 mg/g – Ferrentino
et al. (2018)
ACT: acetone; ETOH: ethanol; HMG: homogenization; MEOH: methanol; Mag-str: magnetic stirring; MCT: maceration; n.i: not informed parameter; SLR: solid to liquid
ratio; RT: room temperature; SX: Soxhlet; TPC: calculated in terms of total phenolic content depending on the study cited.
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
5
high content of polyphenol oxidase, such as apple-based products (Illera
et al., 2019), since drying above the polyphenol oxidase’ inactivation
temperature may be useful to preserve the raw material polyphenols.
Several works used magnetic stirrer as a conventional extraction
technique to obtain phenolics from apples. Among the advantages of this
method are the mild temperatures, which are favorable to extract
thermolabile compounds. Another alternative to overcome temperature
downsides is increasing extraction time.
Fromm et al. (2013) evaluated different temperatures (0–42 ◦C) and
extraction time (60–1440 min) to extract phenolics from apple seeds,
and the authors observed a higher yield of phenolics at 25 ◦C for 60 min.
Da Silva et al. (2020) and Hern´
andez-Carranza et al. (2016) used mag-
netic stirrer to extract phenolics from apple pomace. In both cases, 60 ◦C
was the optimum temperature, but the use of methanol (80%, v/v) and
ethanol (50%, v/v) by Da Silva et al. (2020) resulted in a shorter
extraction time (30 min) than that obtained by Hern´
andez-Carranza
et al. (2016) (720 min), who used water as the solvent. On this subject, it
is worth mentioning that the magnetic stirrer is an alternative to lab-
scale extraction that must be replaced by the mechanical stirrer to
higher processing scales. In addition, such extraction methods need later
processes to separate the solids from the extracts, which impacts the cost
and time to carry out a batch. This issue is not problematic on laboratory
scales; however, it can generate difculties and the need for high-
capacity ltering equipment on industrial scales.
During an extraction procedure, the SLR plays a fundamental role.
An adequate proportion is needed to release the bioactive compounds in
the solvent efciently and, consequently, achieve an adequate extrac-
tion (Rostagno et al., 2010). It is important to highlight that the ideal
ratio used in the extraction process depends on the interaction between
matrix (biomass) and solvent; the biomass particle and their interaction
with the solvent directly inuence the viscosity of the solution, which
affects the mass-transfer coefcient and the extraction efciency.
Additionally, the extraction yield is limited by the target compounds’
solubility in the solvent; therefore, the amount of solvent must ensure
that it is enough to solubilize all the target compounds in the raw ma-
terial. However, excess solvent diminishes the extract concentration and
raises the procedure cost due to the solvent cost and the higher solvent
mass to be evaporated from the extract. Hence, the economic evalua-
tions are very welcome to dene based on production cost the best SLR.
The published paper generally denes the SLR based on the higher yield
or extract concentration without considering cost issues. Moreover,
especially for dried apple-based raw materials, high SLR is not advised
since the pectin extraction may increase the solution viscosity and
diminish the recovery of the compounds. Examples of SLR are reported
by Grigoras et al. (2013) that used maceration to recover phenolics from
apple pomace using an SLR of 0.1 and Hern´
andez-Carranza et al. (2016)
that used SLR of 0.004.
The increased concern about the environmental issues due to the
waste generated after the extraction processes and the costs of operation
and the safety of the workers have stimulated the chase for alternative
methods that are cleaner, cheaper, and eco-friendly. Conventional
methods can generate satisfactory results, and indeed, some of them are
used at industrial scales for different raw materials; however, based on
the drawbacks mentioned above and the need to change classical
manufacture production, non-conventional techniques come out as
feasible options.
3.2. Non-Conventional extraction techniques
The use of non-conventional extraction techniques to recover
bioactive compounds has signicantly increased in the past decade.
Classied by some authors as green techniques, they have many ad-
vantages compared to the conventional ones, such as shorter extraction
time, better temperature control, lower sample and extract light expo-
sition, scalability, selectivity that impacts the extract concentration, and
higher extract yields. Moreover, non-conventional techniques allow the
use of a lower amount of solvent, and in some cases, besides the solvent
is dened as GRAS, it is cyclically recycled (Belwal et al., 2018; Chemat
et al., 2019). The most common methods employed to obtain bioactive
compounds from natural matrices are UAE, MAE, PLE, and SFE (Da Silva
et al., 2020; Ferrentino et al., 2018; Moreira et al., 2017; Wang et al.,
2019).
3.2.1. Ultrasound-assisted extraction (UAE)
The ultrasound-assisted extraction (UAE) has been used to obtain a
broad spectrum of natural compounds through ultrasonic bath and/or
ultrasonic probe. The ultrasound (US) allows continuous compression/
decompression cycles of the bubbles inside the extraction solvent that
cause the cavitation phenomena (He et al., 2016). In addition, the US
may act in the extraction by single or combined mechanisms, including
fragmentation, erosion, capillarity, detexturation, and sonoporation
(Chemat et al., 2017). The sum of US effects in the extraction medium
facilitates the disruption of the physical structure of the raw material,
diminishes the sample particle size, enhances diffusional and convective
mass transfer, and, therefore, increases the extraction efciency by a
better solute–solvent contact.
Table 3 summarizes the UAE’s main works to obtain phenolic com-
pounds from apple by-products, including their operational parameters,
type of US device, and most important compounds analyzed. Ajila et al.
(2011) tested different solvents to extract polyphenols from apple
pomace and concluded that 80% acetone (v/v) promoted the highest
target compounds yield, resulting in three-fold higher extraction ef-
ciency than the same process performed using pure water as the solvent.
Da Silva et al. (2020) evaluated the effects of different solvents (pure
water, ethanol (50–100%, v/v), and methanol (50–100%, v/v/)) on the
extraction of phenolics from apple pomace, being 80% methanol (v/v)
the best solvent for recovering phenolic compounds.. Organic solvents,
such as ethanol or its mixtures, are the most indicated to extract phe-
nolics (e.g., avonoids) from apples (Grigoras et al., 2013; Yue et al.,
2012).
Withouck et al. (2019) showed no signicant differences when
extracting phenolics from apple wood with organic solvent mixtures
between 40 and 80% (v/v solvent/water), at 60 ◦C, for 30 min using
UAE. However, ethanol was signicantly better than others (methanol
and acetone) in extracting these compounds. In contrast, pure water is
the most suitable to extract polar compounds such as phenolic acids
(Pingret et al., 2012; Wang et al., 2018; Wiktor et al., 2016).
Different properties of each solvent are responsible for enhancing the
extraction of a specic class of compounds. Water acts as an emollient of
the samples eluting the highest polar compounds, while organic solvents
easily penetrate in the samples extracting compounds with less polarity
than those extracted by water (Azmir et al., 2013; Da Silva et al., 2020;
Wang et al., 2018, 2019; Yue et al., 2012). Thus, extractions with a
gradient solvent (more polar to less polar, or vice versa) could be an
excellent alternative for recovery sequentially different compounds in
specic fractions, optimizing the full potential of the biomass. Besides,
attention must be paid to using solvents with a low boiling point
because, depending on the ultrasound power and exposure time, the
solvent temperature may reach the boiling temperature, which causes
solvent loss by volatilization.
Temperature is another parameter that needs to be carefully
controlled in UAE since the mechanical process of the ultrasonic waves
may be dissipated as heat, resulting in overheating the solvent and
degradation of the aimed compounds (Chemat et al., 2011). Also, the
heat transferred to the system can generate an additional cost to the
process (in costs and environmental terms).
For example, Grigoras et al. (2013) extracted phenolics from apple
pomace using ethanol as the solvent at room temperature. Otherwise,
Pingret et al. (2012) tested different temperatures (10 to 40 ◦C) using
ethanol as the extraction solvent for recovery phenolic compounds from
apple pomace. They noticed that the highest extraction yields were
obtained at 40 ◦C, using 50% ethanol, 0.142 W/g, 25 kHz, in 45 min, and
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
6
Table 3
UAE and MAE applied to obtain phenolics from apple including the operational parameters, the most important compounds analyzed, and the best conditions reported.
Technique Sample Solvent
(%, v/v)
Temperature
(◦C)
Time
(min)
Frequency
(kHz)
Power (W) SLR (g/
mL)
Most important compounds
analyzed
Yield of
extraction
(TPC)
Best
conditions
tested
References
US bath Apple
pomace
Water
ACT
60–80
ETOH
60–80
MEOH
60–80
40 30 n.i n.i 0.05 n.i n.i. 80% ACT, 30
min, 40 ◦C
Ajila et al.
(2011)
US bath Apple
pomace
Water 9.9–40 5–55 25 0.335–0.764
(W/cm
2
)**
– (−)Epicatechin, Phloridzin,
Chlorogenic Acid
5.55 mg/g Water, 40 ◦C,
40 min, 0.764
W/cm
2
Pingret et al.
(2012)
US bath Unripe
Apple
ETOH
50–70
50–70 20–30 n.i 420–560 0.04 (-)-Epicatechin, Procyanidin
B2, Chlorogenic Acid,
Procyanidin B1
13.26 mg/g 50% ETOH,
519.39 W, 30
min, 50 ◦C
Yue et al.
(2012)
US bath Apple
pomace
ETOH RT 30 n.i n.i 0.05 Gallic Acid, Chlorogenic Acid,
Catechin, Rutin, Ursolic Acid,
Phloridzin
n.i. – Grigoras et al.
(2013)
US bath Fresh,
old and
apple
peel
MEOH
40–100
MEOH
(0.1%
HCl)
RT 5–15 n.i. n.i. 0.04–0.1 Flavonols, Anthocyanins,
Dihydrochalcones, Flavan-3-
Ols
0.181 to
4.992 mg/g
80% MEOH,
15 min
Jakobek et al.
(2015)
US bath Apple Water 20 0–30 21 or 40 180 0.25 n.i 5.43 and
10.46 mg/g
Water, 20 ◦C,
21 kHz, 30 min
and 180 W or
Water, 20 ◦C,
40 kHz, 5 min
Wiktor et al.
(2016)
US bath Apple
pomace
Water
ETOH
Water
(1%
Rokanol)
20 30 n.i. n.i. 0.05 Catechin, Quercetin,
Phloretin derivates, p-
coumaryl-quinic,
Cryptochlorogenic,
Chlorogenic acid
0.88 mg/g ETOH, 20 ◦C,
30 min, SLR
0.05
Malinowska
et al. (2018)
US bath Apple
peel and
pulp
MEOH
20–100
20–80 20–40 35 n.i. 0.06–0.02 Chlorogenic Acid,
Epicatechin, Phloridzin,
Catechin, Hyperoside,
Quercitrin
n.i. MEOH 100%,
33 min, 65 ◦C
(peel) or 20%
MEOH, 40
min, 80 ◦C
(pulp)
Mihailovi´
c
et al. (2018)
US bath Apple
wood
Water
ETOH
20–100
MEOH
20–100
ACT
20–100
60 30 n.i. 800 0.01 Epicatechin gallate,
Kaempferol-3-glucoside,
Naringin, Naringenin, Rutin,
Phloridzin, Phloretin,
Procyanidin B1, Procyanidin
B2, Vanillic acid, Gallic acid,
Ferulic acid, p-Coumaric acid,
Caffeic acid
29 mg/g Ethanol 40 –
80%, 60 ◦C,
30 min, 800 W
Withouck et al.
(2019)
US bath Apple
pomace
Water
ETOH
50–100
MEOH
50–100
60 30 37 n.i. Gallic Acid/Protocatechuic
Acid Glucoside (Pcag),
Chlorogenic Acid,
Epicatechin, Rutin,
Hyperoside, Quercetin
Derivatives, Quercetin
Rhamnoside, Phloretin
Xylosyl Glucoside, Phlorizin
– MEOH 80, 30
min, 60 ◦C, 37
kHz
Da Silva et al.
(2020)
US probe Flesh
and
apple
peel
Water 50 180 24 0–118 0.1 Catechin – – Wang et al.
(2018)
US probe Apple
peel
ETOH
0–96
25–40 30 24 0–400 0.1 n.i – 50% ETOH,
50 W
Wang et al.
(2019)
UAMME Apple
pomace
Water
ETOH
Water
(1%
Rokanol)
20 30 n.i. n.i. 0.05 Catechin, Quercetin,
Phloretin derivates, p-
coumarylo- quinic,
Cryptochlorogenic,
Chlorogenic acid
6.99 mg/g Water (1%
Rokanol),
20 ◦C, 30 min,
SLR 0.05
Malinowska
et al. (2018)
MAE Apple
pomace
Water
ACT
60–80
ETOH
60–80
MEOH
60–80
30–80 5–15 – 400 0.05 n.i 16.12 mg/g 80% ACT, 10
min, 40–60 ◦C
Ajila et al.
(2011)
MAE RT 1.5 – 1000 0.05 n.i. –
(continued on next page)
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
7
water at 40 min and 0.764 W/cm
2
, respectively.
Yue et al. (2012) studied the phenolic extraction from unripe apple
varying temperature and extraction time from 50 to 70 ◦C, and from 20
to 30 min, respectively. The authors observed that the lowest tempera-
ture and the longest time generated the highest total phenolic yield
(13.26 ±0.56 mg GAE/g). Mihailovi´
c et al. (2018) evaluated different
temperatures (20–80 ◦C) and extraction time (20–40 min) to obtain
phenolics from apple skin and pulp. In this case, 65 ◦C and 33 min, with
pure methanol, were considered the optimum conditions for apple skin,
while 80 ◦C and 40 min with 20% methanol was the best condition for
the pulp; therefore, different matrixes and solvents composition slight
interfered with the results about time and temperatures.
Still, regarding the temperature, according to a review work recently
provided by Kumar et al. (2021), the higher temperature UAE operation
may affect the extraction yield by three different hypotheses. One de-
scribes that high temperature increases solvent vapor in the cavitation
bubble reducing the pressure gradient inside and outside the bubble.
Therefore, even though the number of cavitation bubbles is signicant,
they implode with less intensity at a high temperature, causing lesser
damage to the cell and decreasing the yield.
The second hypothesis includes that the increased shear stress causes
the degradation of the desired component due to the large number of
cavitation bubbles formed at higher temperatures and subsequent
collapse. Moreover, the third hypothesis regards reducing the solvent
surface tension at higher temperatures, reducing the cavitation bubble’s
intensity. Thus, the temperature must be carefully evaluated to deter-
mine the specic range that potentializes the extraction performance
and prevents the target compounds’ degradation.
In addition to temperature, frequency and US power are the most
studied parameters in UAE. Table 3 shows that the frequency interval
applied to recover phenolic compounds from different apple samples
varied from 21 to 40 kHz. Low-frequency US (<120 kHz) has been re-
ported to be preferable in extracting bioactive compounds from natural
raw materials; the low-frequency US allows forming a smaller number of
cavitation bubbles with a large diameter than the high-frequency US
(>120 kHz). Higher bubbles enhance the cavitation effect by damaging
the cell structure and releasing the target compounds, increasing the
extraction yield (Kumar et al., 2021; Chemat et al., 2017).
Interestingly, Wiktor et al. (2016) evaluated the effects of frequency
(21 or 40 kHz) and extraction time (0–30 min) on the phenolics from
apple tissue after being treated by US, concluding that 21 kHz for 30 min
or 40 kHz for 5 min displayed the highest yield of total phenolics
compounds of extraction namely, 543.4 ±21.3 and 1046.5 ±18.9 mg
chlorogenic acid/100 g d.m.. The results reported by the authors suggest
that the increase in the frequency requires less extraction time and result
in higher yield, and therefore there could be a frequency inection point
to maximize the extraction yield. However, frequency is still a fertile
eld for research since few studies are available focusing on the effect of
this parameter. Besides, very-high frequencies (beyond 500 kHz) may be
applied for reversible and irreversible sonoporation similar that occurs
in the biological application (molecules cell uptake and cell destruction,
respectively) (Chemat et al., 2017); however, this issue also deserves
further research to be validated for extraction of natural materials.
US power is also a crucial parameter to optimize UAE since it affects
the aforementioned US mechanisms that impact the extraction perfor-
mance. Pingret et al. (2012) reported a direct relation of the US power
with the extraction yield of phenolics from apple pomace. On the other
hand, Yue et al. (2012) evaluated US power (420–560 W) to extract
phenolics from unripe apples. They observed that the highest power
diminished the compounds’ recovery, where 50% ethanol (v/v) at
519.39 W, 30 min, and 50 ◦C, the optimum between the tested
conditions.
Wang et al. (2019) studied different temperatures (25–40 ◦C) and
ultrasonic power (0–400 W) to extract polyphenols from apple skin
using ultrasonic probes. Counterintuitive, the authors noticed that the
optimum condition was achieved at lower power (50 W) in a shorter
extraction time (30 min). Thus, along with the temperature and due to
the same reasons, the US power must be carefully evaluated. Works have
reported that the increase in the US power favor the extraction yield up
to a certain point, and above of it, the US mechanisms are affected by the
bubbled formed; a high concentration of high bubbles leads to an inter-
bubble collision, deformation, and nonspherical collapse resulting in the
less impact between bubbles and raw material, which negatively impact
the yield (Kumar et al., 2021). Moreover, the very high power may affect
the extraction yield of target compounds due to molecular degradation,
especially when high powers are combined with water as solvent. The
Table 3 (continued )
Technique Sample Solvent
(%, v/v)
Temperature
(◦C)
Time
(min)
Frequency
(kHz)
Power (W) SLR (g/
mL)
Most important compounds
analyzed
Yield of
extraction
(TPC)
Best
conditions
tested
References
Apple
pomace
ETOH
Ethyl
Acetate
Water:
MEOH
Gallic Acid, Chlorogenic Acid,
Catechin, Rutin, Ursolic Acid,
Phloridzin
Grigoras et al.
(2013)
MAE Apple
pomace
Water
ETOH
35–100
RT 5–20 – 90 – 360 0.1 – 0.3 n.i. 127 mg/g 90 W, 15 min, Rezaei et al.
(2013)
MAE Apple
tree
wood
ACT 70
ETOH 60
RT 0.5–3 – 100–900 0.083–0.25 Phloridzin, Caffeic Acid,
Chlorogenic Acid, Quercetrin
15.8 mg/g SLR 0.09, 60%
ETOH, 735 W,
2.48 min
Chandrasekar
et al. (2015)
MAE Apple
dust
ETOH
40–80
RT 15–35 – 400–800 0.1 n.i. 30.79 mg/g 40% ETOH,
25 min, 400 W
Pavli´
c et al.
(2017)
MAE Apple
tree
wood
residues
Water
ETOH
20–100
MEOH
20–100
66–134 3–37 – n.i 0.004 Phenolics Acids, Phloridzin,
Myricetin, Kaempferol-3-O-
Glucoside, Naringin and
Quercetin-3-O-
Glucopyranoside
47.7 mg/g 60% ETOH,
20 min, 100 ◦C
Moreira et al.
(2017)
MAE Apple
skin
ETOH
20–100
90–150 30–90 – n.i. 0.1 Epigallocatechin gallate,
Rutin Quercetin, Gallic acid,
Catechin and Protocatechuic
acid
50.4 mg/g Casazza et al.
(2020)
ACT: acetone; ETOH: ethanol; MEOH: methanol; n.i: not informed parameter; RT: room temperature; TPC: calculated in terms of total phenolic content depending on
the study cited; UAMME: ultrasound-assisted micelle-mediated extraction. *Ultrasonic power expressed as power (W) to mass of sample (g) ratio. **Ultrasonic in-
tensity expressed as power (W) per area of the internal diameter of the ultrasound reactor (cm
2
).
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
8
US can dissociate the water molecules in free radicals that may trigger
the oxidation of compounds and breakage of the bonds (Dias et al.,
2021).
The type of ultrasonic device is another determinant parameter that
inuences the extraction yield. Baths and probes are the ultrasonic de-
vices usually used. Ultrasonic baths are the most widely available and
cheap. In this conguration, the energy may be spread out in the vessel
to be transferred to the sample. Besides, in baths, the ultrasonic waves
may have difculties penetrating smaller particles, taking longer
extraction times and diminishing the extraction efciency (Chemat
et al., 2017).
In contrast, ultrasonic probes induce the transfer of ultrasonic energy
directly to the medium. Consequently, cavitation phenomena are more
pronounced, improving the extraction yields (Dias et al., 2017). On the
other hand, direct contact of the probe with the medium can contami-
nate the extract with metals due to erosion. Additionally, ultrasonic
probe processes only one sample at a time, while ultrasonic baths allow
processing several samples simultaneously (Dias et al., 2021).
Ultrasound technology has proven effective in extracting various raw
materials, mainly due to increased extraction yield and reduced pro-
cessing time. However, the technology still has several challenges to
overcome, especially for industrial scales; evidence indicates that it is
necessary to consider the cost of implementation and energy consump-
tion (greener processes must demand less energy). In this sense, the
application of ultrasonic waves at specic moments of the process
should be experimentally and economically validated. For instance,
application at the beginning of the extraction process can accelerate
solvent saturation. Similarly, application at the end of the extraction
process can increase the diffusional mass transfer rate (Dias et al., 2021).
In both cases, time and energy can be saved. Another critical aspect to
consider is the scale-up; it is advisable to keep the energy density con-
stant (J/m
3
) in the scale transposition, implying in the power increase
proportionally to the new volume, or else the extraction time will need
to be extended. Accordingly, ultrasonic probes are restricted for scales of
small volume; alternatively, continuous systems or ultrasonic baths with
a larger radiating surface and an agitation system could be used (Chemat
et al., 2017; Dias et al., 2021).
3.2.2. Microwave-assisted extraction (MAE)
The combination of solid–liquid extraction with microwave radia-
tion is dened as microwave-assisted extraction (MAE). Briey, MAE is
applied to extract soluble products in a uid using microwave energy to
heat the solvent-sample mixture, accelerating the vegetable matrices’
cell walls’ crack (or rupture). Moreover, microwave energy modies the
biological tissues’ physical properties, improving access through the
porosity and the extraction yields (Kubra et al., 2016). Generally, the
solvent’s choice to extract phenolics compounds from apples is based on
solvents with water. The water’s high dielectric constant is a crucial
point in MAE since the microwave absorption depends on the solvents’
higher polarity. The higher absorption of the waves promotes an
increment in the mixture’s temperature, cell disruption, and conse-
quently a better extraction of the compounds from the matrix (Bouras
et al., 2015).
Open and closed systems can be used in MAE. The extraction in open
systems is performed at atmospheric pressure. Consequently, the
maximum temperature is dened by the solvent boiling point, and losses
of vapors can be prevented by cooling systems on the top of the
extraction vessel that promotes the condensation of vapors. Closed
systems avoid this problem by pressure increase and allow temperatures
above the critical point. However, the temperature rises rapidly in
closed systems, difculting the temperature control, damaging ther-
molabile compounds. Therefore, the temperature should be sufcient to
enhance the extraction yield, however not high enough to degrade the
target compounds (Rostagno & Prado, 2013).
Table 3 also summarizes the studies that extracted phenolic com-
pounds from apples by MAE. The main operational parameters, the most
important compounds analyzed, and the best conditions reported are
shown.
Ajila et al. (2011) studied the effects of different solvents, tempera-
ture, and time on the MAE of phenolics from apple pomace, concluding
that 80% methanol (v/v) at 40–60 ◦C for 10 min promoted the best
extraction yield (16.12 mg/g). In a similar approach, Chandrasekar et al.
(2015) tested the inuence of different solvents, time, and power on the
extraction performance of phenolics from apple tree wood. In this case,
the best condition was achieved for 60% ethanol (v/v) at 735 W for 2.5
min yielding 15.8 mg/g. The authors showed that the interaction be-
tween solvent and power was signicant and inverse, which means that
the extraction yield rises when one parameter increased and the other
decreased. In another study, Rezaei et al. (2013) concluded that
increasing microwave power from 90 W to 360 W decreases extraction
yields (127 to 104 mg TAE/g d.m.). They also observed 65% ethanol
with SLR at 0.2 for 15 min, and power of 90 W was better to extract
phenolic compounds from apple pomace using MAE. It is worth
mentioning that the power choice needs to consider a combination with
other operational parameters (e.g., temperature, solvent concentration,
time) to achieve a complete optimized process.
According to Table 3, the temperature used in the studies to recover
phenolics from apples by MAE ranged from 30 to 134 ◦C. Moreira et al.
(2017) evaluated the effects of different solvents (pure water, ethanol
(20–100%, v/v), and methanol (20–100%, v/v)), temperature
(66–134 ◦C), and time (3–37 min) to extract phenolics from apple tree
wood residues. The use of 60% ethanol (v/v) at 100 ◦C for 20 min was
considered the best condition, recovering 47.7 ±0.9 mg GAE/g d.m.
that included phenolic acids, phloridzin, myricetin, kaempferol-3-o-
glucoside, naringin, and quercetin-3-o-glucopyranoside. On the other
hand, Pavli´
c et al. (2017) showed that the lowest yield of phenolics from
apple dust was found in MAE extraction processes where the investi-
gated parameters were higher (60% ethanol, 35 min at 800 W). More-
over, they showed that only factors such as time and ethanol
concentration and their interaction were signicantly relevant (p <
0.05) in the recovery of total phenolics. That is, the longer time may
promote the degradation of sensitive compounds during the extraction
process.
Casazza et al. (2020) identied that the higher the proportion of
organic solvent (ethanol), temperature, and time, the higher the re-
covery of total avonoids (13.9 mg catechin equivalents/g d.m.) for
extracting avonoids sub-class (such as epigallocatechin gallate, rutin,
quercetin, gallic acid, catechin, and protocatechuic acid) from apple
skin using MAE. However, further experiments are necessary to under-
stand the relationship between temperature and other operational pa-
rameters when extracting phenolics from apples by MAE, especially the
stability of compounds.
To sum up, MAE has been developed over several years at laboratory
scales to overcome scale-up limitations. Nowadays, the technology be-
comes a reality and, although a limited few studies underline the po-
tential of MEA at industrial scales, some industrial or pilot installations
can offer the possibility to extract around 100 kg of fresh material.
3.2.3. Pressurized liquid extraction (PLE)
Another alternative and potentially greener technique used to
recover bioactive compounds from vegetable matrices is the PLE, also
called accelerated solvent extraction (ASE), among others. PLE has some
advantages, such as faster extraction time, reduced solvent consump-
tion, and precise adjustment of the operational parameters (Machado
et al., 2015). Moreover, GRAS solvents (e.g., water and/or ethanol)
make the process safer for the operators and less pollutant than con-
ventional techniques. PLE can operate at higher temperatures (above the
boiling point of the solvent) since the solvent is pressurized, with allows
the solvent kept in the liquid state; such a feature enhances the solvent
properties and increases the desorption and solubility of the aimed
compounds (Mustafa & Turner, 2011).
Table 4 shows the reports of PLE to recover phenolic compounds
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
9
from apple and apple by-products, including the most important com-
pounds analyzed and the best conditions reported.
Alonso-Salces et al. (2001) studied the effects of different solvents
(pure water and methanol (100%, v/v)), temperature (40–100 ◦C),
extraction time (5–15 min), and pressure (6.89–10.34 MPa) to obtain
phenolics from apple skin and pulp, concluding that 40 ◦C, 6.89 MPa,
and 5 min was the optimum operating condition to recover phenolic
compounds. Temperatures above that diminished the yield by hydro-
lysis or polymerization reactions.
Wijngaard and Brunton (2009) used PLE to extract phenolics from
apple pomace in different ethanol concentrations (14–85%, v/v) and
temperatures (64–135 ◦C or 153–200 ◦C) at 10.3 MPa. Milder temper-
atures (75–125 ◦C) promoted a better extraction yield (1442 ±58 mg
GAE/100 g d.m.) of total phenolics at 102 ◦C. Further increase in tem-
perature (up to 200 ◦C) was concluded to form undesirable products,
such as hydroxymethylfurfural.
Divergences regarding the optimal temperature for obtaining
bioactive compounds are recurrent in the literature. Therefore, it is
essential for the scientic community to critically analyze the results
when the temperature is evaluated. For example, it is understandable
that the total phenolic yield increases even at high temperatures
(>100 ◦C), as there may is, in addition to extraction, the hydrolysis of
the lignocellulosic material into phenolic acids and other compounds,
contributing to confusion when comparing results and the phenomena
governing the process, and thus, the yield. This effect is particularly
relevant when evaluating results based on spectrophotometric analysis,
such as total phenolics, which can be affected by many compounds,
leading to conicting observations. Therefore, a critical analysis of each
target compound individually is necessary, and with that, a better and
deeper understanding of the effect of temperature can be achieved.
Franquin-Trinquier et al. (2014) obtained phenolics by PLE from
apple using pure methanol and acetone (70%, v/v) at room temperature
and 1 MPa, during extraction intervals of 1 to 15 min, and extraction
cycles from 1 to 3. The authors noticed that pure methanol was the most
suitable solvent to extract chlorogenic acid, hyperoside, quercitrin, and
ideain, for 15 min and three extraction cycles.
Da Silva et al. (2020) recovered phenolics from apple pomace by PLE
and other techniques (UAE, shaker, and magnetic stirring). The authors
employed different solvents (pure water, ethanol (50–100%, v/v) and
methanol (50–100%, v/v)) at 60 ◦C, 10 MPa for 30 min, being methanol
Table 4
Summary of studies that applied PLE and SFE to obtain phenolic compounds from apple including the operational parameters, the most important compounds
analyzed, and the best conditions reported.
Technique Sample Solvent
(%, v/v)
Temperature
(◦C)
Time
(min)
SLR
(g/
mL)
Pressure
(MPa)
Most important compounds
analyzed
Yield of
extraction
(TPC)
Best conditions
reported
References
PLE Apple
peel and
pulp
Water
MEOH
100
40–100 5–15 0.09 or
0.13
6.89–10.34 (+)- Catechin, Procyanidin B2,
(−)-Epicatechin, Procyanidin,
Phloretin-2′-Xyloglucoside,
Phloridzin, Hyperoside,
Isoquercitrin, Quercetin
Glycosides +Rutin, Avicularin,
Quercitrin, Chlorogenic Acid, P-
Coumaric Acid derivative
n.i. 40 ◦C, static
extraction time
(5 min), 6.89
MPa, 2
extraction
cycles
Alonso-
Salces et al.
(2001)
Apple
pomace
ETOH
14–85
64–135 or
153–200
5 0.04 10.3 Chlorogenic Acid, Caffeic Acid,
P-Coumaric Acid, Quercetin
Glycoside, Rutin, Quercetin
Glycoside, Quercetin Glycoside,
Phloretin Glycoside
14.42 mg/g 60% ETOH,
102 ◦C
Wijngaard &
Brunton
(2009)
Apple
pomace
ETOH 40 15 0.08 10 Gallic Acid, Chlorogenic Acid,
Catechin, Rutin, Ursolic Acid,
Phloridzin
n.i. – Grigoras
et al. (2013)
Apple MEOH
ACT 70
RT 1–15 0.007
– 0.07
1 Flavan-3-Ol Monomers
((+)-Catechin,
(−)-Epicatechin), Phloridzin,
Chlorogenic Acid, Hyperoside,
Isoquercitrin, Quercitrin
4.113 mg/g MEOH, 15 min,
3 extraction
cycles
Franquin-
Trinquier
et al. (2014)
Apple
pomace
Water
ETOH
50–100
MEOH
50–100
60 30 0.04 10 Gallic Acid/Protocatechuic Acid
Glucoside (Pcag), Chlorogenic
Acid, Epicatechin, Rutin,
Hyperoside, Quercetin
Derivatives, Quercetin
Rhamnoside, Phloretin Xylosyl
Glucoside, Phlorizin
– ETOH 50–80%,
30 min, 60 ◦C,
10 MPa
Da Silva
et al. (2020)
SFE Apple
pomace
CO
2
+
ETOH
75
50 180 0.27 25 Chlorogenic Acid, Catechin,
Epicatechin, Phloridzin,
Quercetin-3-Glucoside,
Quercetin-3-Galactoside,
Quercetin-3-Arabinoside,
Quercetin-3-Xyloside,
Quercetin-3-Rhamnoside
– CO
2
+25 mol%
cosolvent (96%
ETOH), 25
MPa, 50 ◦C
Massias et al.
(2015)
Fresh
apple
pomace
CO
2
+
ETOH 5
45–55 120 n.i. 20 and 30 P-OH Benzoic Acid, Phlorizin,
Epicatechin, Quercetin,
Phloretin
8.87 mg/g 5% ETOH (co-
solvent), 30
MPa, 45 ◦C,
120 min
Ferrentino
et al. (2018)
Apple
seeds
CO
2
35–60 0–120 0.008
–
0.002
10–30 n.i. 8.21 mg/g 25 MPa, 60
min,
45 ◦C, 2.5 mL/
min
Panadare
et al. (2021)
ACT: acetone; ETOH: ethanol; MEOH: methanol; n.i: not informed parameter; RT: room temperature; TPC: calculated in terms of total phenolic content depending on
the study cited.
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
10
(50–80%, v/v) the best solvent to extract phenolics acids and avonoids.
They found higher amounts of those compounds in PLE than in the other
techniques (at least the double yield compared to conventional
processes).
Although PLE is very useful to reach higher yields in shorter
extraction times, it is not a selective technique. Thus, the authors discuss
that for better extraction performance, it is desirable the association/
coupling of some different techniques (as SPE) in order to concentrate
the extract in the target compounds, improving not only the yield of
extraction but also the selectivity, which could assist in the further
application of the extract. PLE coupled with solid-phase extraction (SPE)
was the one that best recovered phenolics from apple pomace, with
recoveries of phenolic acids equal to 2.85 ±0.19 mg/g and avonoids
equal to 0.97 ±0.11 mg/g. The chase for alternative solvents also can be
a strategy to improve the selectivity of the compound of PLE. As evi-
denced, mostly organic solvents and water have been used and, there-
fore, with the formulation of new solvents as eutectic solvents and ILs,
other options are available and could be used as the main solvent or as a
cosolvent in ethanol or water.
PLE has been widely employed for lab-scale applications, and studies
report it in general as the most efcient (high extraction yields and less
extraction time) to obtain polar compounds being economically feasible
at large scales (Vigan´
o et al., 2017). Besides that, PLE is easily scalable
and automated. Nonetheless, the literature lacks studies performing
scale-up to ensure that the extraction yields and extract composition
have reproducibility at large scales. Along with scale-up, coupling PLE
with other extraction methods is also a perspective, mainly due to
integrating processes to accomplish the biorenery concept.
3.2.4. Supercritical uid extraction (SFE)
Although it has many advantages, among the non-conventional
techniques, the SFE is the less used to process apple-based raw mate-
rials, probably because SFE is an excellent candidate for extracting
nonpolar compounds that are in low concentrations matrices. Moreover,
SFE appears as a clean and eco-friendly alternative to recover bioactive
compounds. The main advantages of SFE compared to conventional
techniques are the use of milder temperatures, reduced solvent amount,
higher purity of the extracts (i.e., selectivity), and reduced energy costs.
The most used solvent in SFE is carbon dioxide (CO
2
), which has
improved mass transfer properties due to its density and viscosity. In
addition, supercritical CO
2
is a GRAS solvent, nontoxic, relatively inert,
and totally recovered at the end of the process (Dias et al., 2016). Be-
sides, in SFE with CO
2
, the solvent-free extract is obtained by the uid
depressurization, which impacts energy savings to evaporate solvents;
besides not leaving residual organic solvent in the nal extract,
contrarily than those techniques dependent on liquid solvents.
A recent study by Panadare et al. (2021) used SFE to extract volatile
compounds from apple seeds and obtained a yield of 8.21 mg GAE/g.
The process parameters were 25 MPa, 60 min, 45 ◦C, ow 2.5 mL/min.
However, SFE can be performed by adding cosolvents (ethanol, water)
to overcome low yields; consequently, the desorption of polar com-
pounds from the vegetable matrices is favored (Xu et al., 2017).
In Table 4, one can note the use of ethanol as the cosolvent added to
CO
2
, enhancing the extraction yield of phenolic compounds from apple
pomace. Massias et al. (2015) extracted phenolics from apple pomace
through SFE at a xed temperature (50 ◦C), extraction time (180 min),
and pressure (25 MPa). Moreover, the authors used a higher ethanol
concentration (75%, v/v) added to CO
2
since the presence of quercetin
glucoside derivatives associated with polar compounds makes these
components less extractable in nonpolar solvents.
Regarding cosolvent applications, it is relevant for the scientic
community to critically consider the amount used since it can have
critical implications (literally). The cosolvent addition changes the
phase equilibrium and can lead the system to conditions outside the
critical region depending on the proportion used. For example, Fer-
rentino et al. (2018) compared SFE to recover phenolics from fresh apple
pomace with and without cosolvent (ethanol (5%, v/v) at pressures of
20 and 30 MPa, temperature intervals from 45 to 55 ◦C for 120 min. The
results showed that an optimum total phenolic compounds extraction
yield was obtained when the cosolvent was employed, as well as the use
of the lowest temperature and the highest pressure. In a supercritical
process, pressure and temperature variation change the CO
2
density and
its solvation power. Therefore, higher densities induce smaller spaces
and higher interactions between the molecules (Dias et al., 2021). From
this point, the authors could infer that pressure and temperature
reduction resulted in a higher solvation power.
As with other techniques, the temperature also needs to be carefully
evaluated in SFE. Depending on the target compounds, the solubility can
have an inverse effect on SFE. Compounds better extracted at high sol-
vent densities will be favored when temperatures closer to the critical
limit are used. On the other hand, for raw materials whose extraction
depends on the vapor pressure of the solutes, the increase in temperature
favors the extraction. Generally, temperatures higher than 80 ◦C is not
usual in SFE, and therefore, thermal degradation is not presented as a
problem for most phenolic compounds.
Analogous to PLE, SFE is easily scaled and automated, and indeed, it
is an extraction method with large-scale industrial applications. How-
ever, as aforementioned, SFE mainly uses CO
2
as the solvent, making it
less efcient to extract phenolic compounds. Considering that, the
application of CO
2
+new cosolvents or even the investigation of other
alternative solvents to CO
2
could be a sensible approach to overcome its
limitations in obtaining compounds of higher polarity.
3.2.5. Sequential extraction processes
The several challenges involved in extracting and purifying com-
pounds from natural products lead to innovative approaches to over-
come them. For example, combining different techniques has been
widely used to recover phenolics from vegetable matrices and enhance
the aimed compounds’ extraction (Vigan´
o et al., 2016). The main ad-
vantages of the combined processes are higher extraction yields, less
solvent amount, shorter time, and higher purication and/or separation
of the nal products (Rostagno & Prado, 2013; Santos et al., 2019; Souza
et al., 2020; Sumere et al., 2018; Wang et al., 2019). Da Silva et al.
(2020) proposed an online extraction/fractionation technique employ-
ing PLE coupled to SPE to increase the purication of phenolics from
apple pomace. PLE-SPE was used at different temperatures (60–80 ◦C),
solvent concentrations (pure water, methanol (0–100%, v/v), and
ethanol (0–100%, v/v)) at 10 MPa during 70 min, and the method was
compared to PLE and other conventional techniques, such as magnetic-
stirrer, shaker, and UAE. The authors obtained two different fractions of
compounds, one of the phenolic acids (yield: 2.85 ±0.19 mg/g) and
another of avonoids (yield: 0.97 ±0.11 mg/g); therefore, PLE-SPE
presented higher extraction yields than the other techniques (3.69- to
1.45-fold higher than produced by PLE, UAE, shaker, and magnetic
stirring).
Besides, some techniques have been used to pre-treatment the apple
fruits to extract the target bioactive compounds, such as enzyme-assisted
extraction (EAE) and pulse electric eld extraction (PEF). EAE may
enhance the mass transfer in extraction processes by breaking the cell
walls of the vegetable matrices (Krakowska et al., 2018). PEF consists of
a technique in which samples are inserted between two electrodes
creating pulses that raise the extraction of the desired components. PEF
has also been employed as a pre-treatment to extract carotenoids and
phenolics from vegetable matrices (Bot et al., 2018). Lohani & Muthu-
kumarappan (2016) noticed that PEF as pre-treatment in apple pomace
enhanced the phenolics release up to 37.4% compared to the control.
EAE can be used to remove non-phenolic compounds (e.g., pectin) from
apples or assist the elution of the phenolics compounds (Wikiera et al.,
2015), which could be a suitable biomass pre-treatment to improve the
phenolics’ extraction selectivity.
To sum up, sequential extraction processes to integrate techniques
and intensify the recovery of target compounds or enhance their
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
11
concentration in the extract are still incipient in the literature. They are
expected to be worthy of investigation remarkably due to the ap-
proaches on biorenery. Due to the concerns in changing the linear to
circular economies, it is expected that the integration of processes could
be more explored shortly, including technical, economic, social, and
environmental aspects, resulting in factual greener platforms to use the
food by-products fully, including apple pomace.
3.2.6. Sustainability and the use of non-volatile alternative solvents
Developing new sustainable downstream processes to recover
bioactive extracts is a clear tendency in the scientic community.
However, much more is needed to create a green process than reduce the
processing time and cost. It is necessary to guarantee higher extract
yields than those conventionally obtained, besides better extract purity
and quality (Chemat et al., 2019; Mesquita et al., 2020). Also, it is
desired that the newly developed process promotes low energy con-
sumption, economic costs, and environmental impacts.
From ancient times, many extraction platforms are mediated by
petroleum-based organic solvents for recovering compounds to be
applied in many industrial sectors, which are not desired considering
their real toxicity potential, besides severe implications on the envi-
ronment (Chemat et al., 2019). Thus, a strategy carried forward is using
water as the extraction solvent, which seems to be the best (and safer!)
alternative for recovering bioactive compounds from biomass. Never-
theless, due to the high-water polarity, water is not suitable for solubi-
lizing a very broad compound. Considering this, some compounds added
in water could modulate the solubility of solutes, such as ILs and eutectic
solvents, enhancing the extraction of certain compounds that are usually
not well recovered.
The ILs are salts with low melting points that can be used as solvents
for selective extraction of a large plethora of biomolecules, from hy-
drophilic (phenolic compounds) (Silva et al., 2017; Lima et al., 2017) to
hydrophobic (carotenoids, chlorophylls, curcuminoids, essential oils)
(Souza Mesquita et al., 2020; Souza Mesquita et al., 2019). Also, ILs have
been considered design solvents due to their unique tunable properties
and eutectic solvents.
However, eutectic solvents are low-transition-temperature mixtures
(of two or more compounds), which cover a large variety of anionic and/
or cationic molecules, for which the eutectic temperature is under that of
an ideal liquid mixture and are used for a myriad of applications
(Hansen et al., 2020). Furthermore, both ILs and eutectic mixtures
present negligible volatility at atmospheric conditions, besides being
considered alternatives for replacing organic solvents in extraction
platforms, which are usually labeled as hazards and ammable (Ventura
et al., 2017).
Therefore, some authors classify these solvents as an environmen-
tally compatible (or green) alternative. Some reports have already
proven the possibility of recycling them without loss of efciency, be-
sides their low toxicity compared to those organic solvents used in the
same extraction process. Another alternative is using an aqueous solu-
tion of surfactants (nonionic or ionic), which are also considered alter-
natives for replacing volatile organic solvents in extraction processes
since their amphiphilic structure can extract both hydrophilic and hy-
drophobic compounds.
In the context of the available reports using apple by-products as a
source of bioactive compounds, IL and eutectic solvents have been
scarcely explored (Table 5). Also, three reports highlighted the use of
aqueous solutions of nonionic surfactants. A conventional approach by
stirring rotation was recently optimized by Skrypnik & Novikova (2020)
for obtaining phenolics from apple pomace. An aqueous polysorbate 80
solution (1.14 %) at room temperature, SLR 0.009 for 64.6 min
extracted 7.75 mg/g of phenolic compounds, representing two-fold the
extraction yield obtained by pure water and ethanol (70%, v/v). Also,
the authors noticed that the antioxidant activity of the surfactant extract
was higher than those extracted by ethanol.
Hosseinzadeh et al. (2013) highlighted that surfactant-water
solution was selected as the best solvent to recover phenolic com-
pounds from whole apple samples, even compared to those where the
surfactant was dissolved in ethanol or methanol. The UAE (bath) was
optimized using Brij-58 (7 mM) at 25 ◦C, recovering between 97 and
104% of the main target compounds from apple. Also, using Brij-58
solution at 7 mM, Sharma et al. (2015) enhanced the extraction per-
formance of total phenolics from apple juice by applying surfactant so-
lution instead of acetone, methanol, and ethanol. Using UAE (bath) at
room temperature for 10 min, the authors recovered 180 mg/g of total
phenolic compounds, besides 90.4% of antioxidant activity.
Imidazolium-based ILs were the most well-investigated for extract-
ing natural compounds from different biomasses, including apple
biomass (Table 5). However, given the signicant possibilities of new
ILs, such as those made with naturally derived ions (more benign, non-
toxic, and low-cost), additional studies are necessary to improve the
safety of the obtained extracts since imidazolium-based ILs were not
considered as the best choice, especially in the food sector due to their
high toxicity (Flieger & Flieger, 2020).
By a conventional approach technique (rotatory elliptical shaking),
de Faria et al. (2017) recovered triterpene acids from apple skin using an
aqueous solution of the tensioactive IL 1-tetradecyl-3-methylimidazo-
lium chloride ([C
14
mim]Cl) at 500 mM, 80 ◦C, SLR 0.1 for 60 min,
representing a promising alternative over the replacement of acetone
and chloroform, the most organic solvents used for this purpose.
A microwave-assisted extraction using 1-Butyl-3-methylimidazolium
bromide ([C
4
min]Br) at 600 mM, 73 ◦C, SLR 0.03 for 15 min was applied
by (Du et al., 2013). The authors recovered only 0.3% of the total
phenolic content from apple pomace, which indeed does not represent a
successful extraction method. However, 181 mg/g of phenolic com-
pounds were extracted from apple owers by using a methanolic solu-
tion of [C
4
min]Br (operational conditions: 520 mM, SLR 0.01, 60 min),
which promoted an increased by 25.4% of the extraction yield compared
to the same process using organic solvents (Li et al., 2012).
Phenolic compounds, like those present in apple biomass, have been
widely extracted by eutectic mixtures from different matrices, namely
grapes (Jeong et al., 2015), olive pomace (Chanioti & Tzia, 2018), and
wood (Alvarez-Vasco et al., 2016), just to mention a few. A high-speed
countercurrent chromatography approach was performed by using
Choline chloride/glucose-ethyl acetate eutectic solvent (75%, molar
ratio: 1:1:2) for extraction of phenolics from Malus hupehensis. Water
was used as a co-solvent under the operational conditions optimized at
77.5 ◦C, SLR 0.04 for 30–90 min. The methodology recovered 15.3% of
the target compounds, which was superior to that obtained by methanol-
mediated extraction (Cai et al., 2021).
Non-volatile solvents allow new combinations in different extraction
techniques to investigate each case’s best scenario. Thus, considering
the countless possibility of alternative solvents that can be formed (~10
8
ternary ILs and 10
6
binary ILs are potentially formed), compared to 600
different organic solvents commonly used in the industrial eld, the
design solvents are the future (and the present!) since it is possible to
modulate a particular solvent for a specic purpose.
However, until now, no sustainable extraction processes have been
developed using apple as a source of bioactive compounds, which is
worrying, considering the large number of tons yearly discarded of this
raw material. Therefore, more studies are needed in order to optimize
not only the extraction performance (yield of extraction), but also the
sustainability of the developed process (especially the recyclability of
solvents) (Souza Mesquita et al., 2021), putting into practice the circular
economy concept.
Besides, it is worth mentioning that the alternative solvents are a tool
to be used in an extraction method and, in this sense, the application of
the new solvent and the method process parameters must be optimized
and studied from lab to large scales. Additionally, new solvents gener-
ally are costly, which leads to two options. First, the new solvent could
give technical or biological roles to the extract that justies the solvent’s
presence in the product. Second and contrarily, the solvent must be
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
12
Table 5
Summary of studies that applied IL, and eutectic solvents to obtain phenolic compounds from apple including the operational parameters and target compounds.
Sample Optimum operating conditions Extracted compounds Yield References
Solvent Co-solvent Concentration Technique Temperature (◦C) Time (min) SLR (g/mL)
Apple peels 1-tetradecyl-3-
methylimidazolium
chloride - [C
14
mim]Cl
Water 500 mM Rotatory elliptical
shaking
80 60 0.1 Ursolic, oleanolic, and
betulinic acids
2.6% Faria et al. (2017)
Apple pomace 1-Butyl-3-
methylimidazolium
bromide - [C
4
mim]Br
Water 600 mM MAE 73 15 0.03 TPC 0.3% Du et al. (2013)
Apple owers 1-Butyl-3-
methylimidazolium
bromide - [C
4
mim]Br
MEOH 520 mM UAE n.d. 60 0.01 Phlorizin, Astragalin, and
Afzelin
181.03 mg/g Li et al. (2018)
Whole apple Choline chloride/
glucose-ethyl acetate -
ChCl/Glu-EAC- molar
ratio: 1:1:2
Water 75 % High-speed
countercurrent
chromatography
based on eutectic
solvent
77.5 30–90 0.04 6 -O-coumaroyl-2 -O-
glucopyranosylphloretin,
3 -methoxy-6 -O-
feruloy- 2 -O-
glucopyranosylphloretin,
vicularin, phloridzin, and
sieboldin
15.% Cai et al. (2021)
Apple pomace Polysorbate 80 - Tween
80® – Surfactant)
Water 1.14 % Stirring rotation RT 64.6 0.009 TPC 7.75 mg/g Skrypnik & Novikova (2020)
Apple juice Brij-58® - surfactant Water 7 mM UAE (bath) RT 10 n.r. TPC 35.4 mg/g Sharma et al. (2015)
Whole apple Brij-58®
-
surfactant +2
% potassium chloride
(W/V), pH =3.7
Water 7 mM UAE (bath) 25 n.i. n.d. Gallic acid, Catechin, Epi-
catechin, Chlorogenic
acid, Coumaric acid,
Fluoridizin, and
Quercetin
180 mg/g Hosseinzadeh et al. (2013)
MAE: microwave assisted extraction; MEOH: methanol n.d.: not described; n.r.: not required step; TPC: calculated in terms of total phenolic content depending on the study cited; SLR: solid–liquid ratio; RT: room
temperature; UAE: ultrasound assisted extraction.
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
13
separated and recycled.
4. Concluding remarks and future perspectives
The available information indicates that many strategies were
explored to overcome the challenges of recovering phenolic compounds
from apples and by-products. Fig. 1 summarizes the data raised by this
work, which was detailed presented in Tables 2–5, and allows an
overview of the extraction methods and their extraction variables that
have been used. According to Fig. 1, magnetic stirring and shaker ho-
mogenization was the preferred conventional techniques employed in
the last two decades. It is worth mentioning that this work identied
majority extraction methods at lab scales; therefore, although these
methods are not considered the most efcient in terms of yield and
selectivity, they are very ready to hand at lab scales, making them the
most applied. Apart from the conventional methods, the UAE is gaining
prominence and is the leading emergent technique, possibly due to its
advantages like short extraction times with comparable or higher yield
of other techniques. Additionally, coupled techniques, such as PLE-SPE,
are yet poorly explored to extract/separate bioactive compounds from
apple raw materials, having only one work published so far (Da Silva
et al., 2020).
Still, it is possible to note in Fig. 1 that the SLR used more times by
the authors ranged between 0.04 and 0.05 g/mL, which can be
considered a good choice for following works aiming to devolop of new
extraction platforms. Mild temperatures (20–30 ◦C) were the most used
in the works, especially in conventional methods. However, tempera-
tures between 51 and 60 ◦C, and higher than 100 ◦C were already
studied with satisfactory results, especially in pressurized systems like
PLE (primarily performed using pressures ranging from 1 to 10 MPa).
The extraction time was the operational condition with more
different ranges, reecting its dependence on other extraction variables.
Regardless of the technique used, most extractions are performed using
times between 10 and 30 min. Here we must make a very important
statement; the behavior of an extraction run shows a typical evolution
with time in which the yield increases with the time until the extractable
fraction is exhausted from the raw material. The optimal time to stop the
run varies with the purpose of the process. For example, in an analytical
application, an extraction time is expected to allow the sample depletion
and achieve the quantitative extraction.
On the other hand, for industrial purposes, it is well documented that
it is not convenient to extract until such time to exhaust the raw mate-
rial. The extraction time impacts the number of batches produced
annually and, consequently, impacts the cost of manufacturing. There-
fore, for industrial applications, it is also advisable to verify the impact
of the extraction time on the cost of manufacturing.
Fig. 1 allows concluding that organic solvents are yet the most used
to extract phenolic compounds from apple-based raw materials
Fig. 1. Distribution of the works dealing with different extraction technique and their respective conditions (solid–liquid ratio (SLR), temperature, time, solvent,
and pressure).
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
14
(unfortunately!). However, despite the large number of works developed
with methanol, acetonitrile, and acetone, the ethanolic solutions with
different concentrations (20–99% v/v) were the most employed so far,
which is a positive point considering that the ethanol has a low toxicity
potential compared to other organic solvents and is not petroleum
derivate. Supercritical CO
2
, ILs, eutectic solvents, and aqueous solutions
of surfactants have already been used but just in few cases still in lab
scales, and more research is needed to discover new possibilities towards
the sustainability of new solvents. Considering the main trends in the
industrial sector are going toward the development of sustainable stra-
tegies for extraction of biobased molecules from wastes, by-products,
and pomaces, shortly we hope to see the scientic community chang-
ing the paradigm from the conventional to the modern, with more
studies focusing on the development of integrated downstream pro-
cesses with recycling of the raw materials and using extraction tech-
niques that meet the green chemistry principles.
Due to the large amount of waste produced annually from the apple
industries, adequate handling and disposal of the residues are needed to
reduce the environmental impacts. In addition to environmental issues,
there are the economic aspects, where the reuse of waste (and by-
products) allows reducing the waste treatment cost. Thus, the extrac-
tion processes using apple-based raw materials are a feasible alternative
to create new products with high added value, creating new market
opportunities in many industrial elds. In this sense, the concept of
transition from linear to circular production systems can be applied to
the chain of apple products. The extraction processes we cover in this
work consist of only one step in this chain and can be integrated with
other processes giving rise to a biorenery. Specically, the chemical
composition of apple pomace enables it to be used in extraction pro-
cesses to obtain phenolic compounds, whose by-products can still follow
in the transformation chain because they have pectin and lignocellulosic
compounds that are interesting for the production of new materials and
energy. Indeed, apple by-products as the pomace have already been
industrially used to produce pectin, ethanol, citric acid, lactic acid, and
enzymes. To the best of our knowledge, such and other processes could
be integrated into a biorenery concept.
Been more restricted to the extraction processes, as presented and
discussed in the previous sections, apple pomace has been widely used
on a laboratory scale to obtain phenolic compounds, mainly phenolic
acids and avonoids. Nevertheless, there is a lack of reports dealing with
coupled extraction techniques. Many published works approach the use
of SFE-UAE to recover bioactive compounds from by-products from food
industries (Dias et al., 2016; Santos et al., 2015). Some other studies
used PLE-UAE to obtain bioactive from food waste, such as pomegranate
peels (Sumere et al., 2018; Santos et al., 2019), defatted passion fruit
bagasse (Vigan´
o et al., 2020).
Moreover, Santos et al. (2019) used the coupled expanded N
2
asso-
ciated with UAE to enhance phenolics recovery from pomegranate peels.
The combination of these techniques, whether in a raw material pre-
treatment or by assisting the entire extraction process, or in pulses,
aims to enhance the extraction process, i.e., increase the yield and
extract concentration, provide less heat to the system, and decrease
consumption solvent and extraction time always with the least envi-
ronmental impact in mind. Therefore, these mentioned coupled
extraction techniques arise as promising possibilities to enhance the
apple by-products processing.
Apart from the extraction technique, the choice of solvent is a critical
step in the process design. Ethanol, water, and mixture have been widely
employed to obtain phenolic compounds. Water is compatible with the
most phenolic extract application; therefore, it does not always need to
be evaporated, unlike ethanol. Consequently, the option for a solvent
that is both efcient to extract and may have functionalities in the
product in which the extract will be applied is very welcome. For
example, Strieder et al. (2020) used milk as a solvent to obtain a blue
colorant from genipap, considering the application in foods.
We want illustrate that the solvent’s choice can go beyond simply
desorbing and solubilizing the extract; the solvent can, for instance, play
as an emulsier and stabilizer in food or as an emollient in drugs and
cosmetics. In this context, ILs and eutectic solvents are good candidates
since they have favorable physicochemical properties. Ionic liquids and
natural deeps eutectic solvents have been reported as solvents for
emerging extraction techniques like UAE and MAE. Accordingly, they
are handled as a perspective to be employed as solvents in emerging
extraction techniques and modern and coupled ones, such as those
where the extraction coincides with the analysis.
Regardless of the extraction technique, to better understand the
bioactive compounds’ mass transfer behavior, mathematical modeling is
recommended in which the solutes’ behavior in sub- and supercritical
media during the extraction procedures can be predicted. Moreover, the
economic analysis and life cycle assessment of the new processes are
helpful and very welcome, especially if the scale-up of the methods is
aimed. Similarly, with the transposition between laboratory and in-
dustrial scales in mind, developing methods to concentrate the extract
on the target compounds is also a fertile eld for research.
Finally, given what was presented in this review, the potential of
apple-based raw materials for obtaining bioactive compounds is reaf-
rmed. In addition to market trends and needs, the apple is grown in all
continents, which provides a good supply chain worldwide showing and
ensures the promising industrial application for producing phenolic
compounds into a biorenery concept.
Declaration of Competing Interest
The authors declare that they have no known competing nancial
interests or personal relationships that could have appeared to inuence
the work reported in this paper.
Acknowledgments
The authors would like to thanks to S˜
ao Paulo Research Foundation
(FAPESP), the National Council for Scientic and Technological Devel-
opment (CNPq), and the Coordination of Superior Level Staff Improve-
ment - Brazil (CAPES) for supporting this research.
Funding sources
This work was supported by S˜
ao Paulo Research Foundation
(FAPESP), S˜
ao Paulo, SP [grant number 2019/13496-0; 2018/14582-5;
2019/24537-0; 2020/15774-5; 2020/08421-9; 2018/17089-8; 2019/
18772-6; 2020/04067-6 and 2020/03623-2]; National Council for Sci-
entic and Technological Development (CNPq) [grant number 151005/
2019-2] and Coordination of Superior Level Staff Improvement - Brazil
(CAPES) [grant number 88887.310558/2018-00 and Finance Code
001].
References
Ajila, C. M., Brar, S. K., Verma, M., Tyagi, R. D., & Val´
ero, J. R. (2011). Solid-state
fermentation of apple pomace using Phanerocheate chrysosporium - Liberation and
extraction of phenolic antioxidants. Food Chemistry, 126(3), 1071–1080. https://doi.
org/10.1016/j.foodchem.2010.11.129
Alberti, A., Zielinski, A. A. F., Zardo, D. M., Demiate, I. M., Nogueira, A., & Mafra, L. I.
(2014). Optimisation of the extraction of phenolic compounds from apples using
response surface methodology. Food Chemistry, 149, 151–158. https://doi.org/
10.1016/j.foodchem.2013.10.086
Alonso-Salces, R. M., Korta, E., Barranco, A., Berrueta, L. A., Gallo, B., & Vicente, F.
(2001). Pressurized liquid extraction for the determination of polyphenols in apple.
Journal of Chromatography A, 933(1–2), 37–43. https://doi.org/10.1016/S0021-
9673(01)01212-2
Alvarez-Vasco, C., Ma, R., Quintero, M., Guo, M., Geleynse, S., Ramasamy, K. K., …
Zhang, X. (2016). Unique low-molecular-weight lignin with high purity extracted
from wood by deep eutectic solvents (DES): A source of lignin for valorization. Green
Chemistry, 18(19), 5133–5141. https://doi.org/10.1039/C6GC01007E
Armenta, S., Garrigues, S., Esteve-Turrillas, F. A., & de la Guardia, M. (2019). Green
extraction techniques in green analytical chemistry. TrAC - Trends in Analytical
Chemistry, 116, 248–253. https://doi.org/10.1016/j.trac.2019.03.016
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
15
Azmir, J., Zaidul, I. S. M., Rahman, M. M., Sharif, K. M., Mohamed, A., Sahena, F., …
Omar, A. K. M. (2013). Techniques for extraction of bioactive compounds from plant
materials: A review. Journal of Food Engineering, 117(4), 426–436. https://doi.org/
10.1016/j.jfoodeng.2013.01.014
Barreca, D., Bellocco, E., Lagan`
a, G., Ginestra, G., & Bisignano, C. (2014). Biochemical
and antimicrobial activity of phloretin and its glycosilated derivatives present in
apple and kumquat. Food Chemistry. https://doi.org/10.1016/j.
foodchem.2014.03.118
Barros, L., Due˜
nas, M., Ferreira, I. C. F. R., Baptista, P., & Santos-Buelga, C. (2009).
Phenolic acids determination by HPLC–DAD–ESI/MS in sixteen different Portuguese
wild mushrooms species. Food and Chemical Toxicology, 47(6), 1076–1079. https://
doi.org/10.1016/j.fct.2009.01.039
Belwal, T., Ezzat, S. M., Rastrelli, L., Bhatt, I. D., Daglia, M., Baldi, A., … Atanasov, A. G.
(2018). A critical analysis of extraction techniques used for botanicals: Trends,
priorities, industrial uses and optimization strategies. TrAC – Trends in Analytical
Chemistry, 100, 82–102. https://doi.org/10.1016/j.trac.2017.12.018
Bolarinwa, I. F., Orla, C., & Morgan, M. R. (2015). Determination of amygdalin in apple
seeds, fresh apples and processed apple juices. Food chemistry, 170, 437–442.
https://doi.org/10.1016/j.foodchem.2014.08.083
Bondonno, N. P., Bondonno, C. P., Ward, N. C., Hodgson, J. M., & Croft, K. D. (2017). The
cardiovascular health benets of apples: Whole fruit vs. isolated compounds. Trends
in Food Science & Technology, 69, 243–256. https://doi.org/10.1016/j.
tifs.2017.04.012
Bot, F., Verkerk, R., Mastwijk, H., Anese, M., Fogliano, V., & Capuano, E. (2018). The
effect of pulsed electric elds on carotenoids bioaccessibility: The role of tomato
matrix. Food Chemistry, 240, 415–421. https://doi.org/10.1016/j.
foodchem.2017.07.102
Bouras, M., Chadni, M., Barba, F. J., Grimi, N., Bals, O., & Vorobiev, E. (2015).
Optimization of microwave-assisted extraction of polyphenols from Quercus bark.
Industrial Crops and Products, 77, 590–601. https://doi.org/10.1016/j.
indcrop.2015.09.018
Budzynska, B., Faggio, C., Kruk-Slomka, M., Samec, D., Nabavi, S. F., Sureda, A., …
Nabavi, S. M. (2017). Rutin as neuroprotective agent: From bench to bedside. Current
Medicinal Chemistry, 26(27), 5152–5164. https://doi.org/10.2174/
0929867324666171003114154
Cai, X., Xiao, M., Zou, X., Tang, J., Huang, B., & Xue, H. (2021). Extraction and
separation of avonoids from Malus hupehensis using high-speed countercurrent
chromatography based on deep eutectic solvent. Journal of Chromatography A, 1641,
Article 461998. https://doi.org/10.1016/j.chroma.2021.461998
Carocho, M., & Ferreira, I. (2013). The role of phenolic compounds in the ght against
cancer – A review. Anti-Cancer Agents in Medicinal Chemistry, 13(8), 1236–1258.
https://doi.org/10.2174/18715206113139990301
Casazza, A. A., Pettinato, M., & Perego, P. (2020). Polyphenols from apple skins: A study
on microwave-assisted extraction optimization and exhausted solid characterization.
Separation and Purication Technology, 240, Article 116640. https://doi.org/
10.1016/j.seppur.2020.116640
Chandrasekar, V., Martín-Gonz´
alez, M. F. S., Hirst, P., & Ballard, T. S. (2015). Optimizing
microwave-assisted extraction of phenolic antioxidants from red delicious and
jonathan apple pomace. Journal of Food Process Engineering, 38(6), 571–582. https://
doi.org/10.1111/jfpe.12187
Chanioti, S., & Tzia, C. (2018). Extraction of phenolic compounds from olive pomace by
using natural deep eutectic solvents and innovative extraction techniques. Innovative
Food Science & Emerging Technologies, 48, 228–239. https://doi.org/10.1016/j.
ifset.2018.07.001
Chemat, F., Abert-Vian, M., Fabiano-Tixier, A. S., Strube, J., Uhlenbrock, L., Gunjevic, V.,
& Cravotto, G. (2019). Green extraction of natural products. Origins, current status,
and future challenges. TrAC - Trends in Analytical Chemistry, 118, 248–263. https://
doi.org/10.1016/j.trac.2019.05.037
Zhi, K., Li, M., Bai, J., Wu, Y., Zhou, S., Zhang, X., & Qu, L. (2016). Quercitrin treatment
protects endothelial progenitor cells from oxidative damage via inducing autophagy
through extracellular signal-regulated kinase. Angiogenesis. https://doi.org/
10.1007/s10456-016-9504-y
Zhou, L., Xiong, Z., Liu, W., & Zou, L. (2017). Different inhibition mechanisms of gentisic
acid and cyaniding-3-O-glucoside on polyphenoloxidase. Food Chemistry, 19(3),
311–324. https://doi.org/10.1016/j.foodchem.2017.05.010
Chemat, F., Zill-e-Huma, & Khan, M. K. (2011). Applications of ultrasound in food
technology: Processing, preservation and extraction. Ultrasonics Sonochemistry, 18
(4), 813–835. https://doi.org/10.1016/j.ultsonch.2010.11.023.
Chemat, F., Rombaut, N., Sicaire, A. G., Meullemiestre, A., Fabiano-Tixier, A. S., & Abert-
Vian, M. (2017). Ultrasound assisted extraction of food and natural products.
Mechanisms, techniques, combinations, protocols and applications A review.
Ultrasonics Sonochemistry, 34, 540–560. https://doi.org/10.1016/j.
ultsonch.2016.06.035
Chen, C. (2016). Sinapic acid and its derivatives as medicine in oxidative stress-induced
diseases and aging. Oxidative Medicine and Cellular Longevity, 2016, 1–10. https://
doi.org/10.1155/2016/3571614
Connor, S., Adriaens, M., Pierini, R., Johnson, I. T., & Belshaw, N. J. (2014). Procyanidin
induces apoptosis of esophageal adenocarcinoma cells via JNK activation of c-Jun.
Nutrition and Cancer, 66(2), 335–341. https://doi.org/10.1080/
01635581.2014.868914
Da Silva, L. C., Souza, M. C., Sumere, B. R., Silva, L. G. S., da Cunha, D. T., Barbero, G. F.,
… Rostagno, M. A. (2020). Simultaneous extraction and separation of bioactive
compounds from apple pomace using pressurized liquids coupled on-line with solid-
phase extraction. Food Chemistry, 318, Article 126450. https://doi.org/10.1016/j.
foodchem.2020.126450
Dachineni, R., Ai, G., Kumar, D. R., Sadhu, S. S., Tummala, H., & Bhat, G. J. (2016).
Cyclin A2 and CDK2 as novel targets of aspirin and salicylic acid: A potential role in
cancer prevention. Molecular Cancer Research, 14(3), 241–252. https://doi.org/
10.1158/1541-7786.MCR-15-0360
D’Archivio, M., Scazzocchio, B., Giovannini, C., & Masella, R. (2014). Role of
protocatechuic acid in obesity-related pathologies. Polyphenols in Human Health and
Disease. Academic Press. https://doi.org/10.1016/B978-0-12-398456-2.00015-3
Dias, A. L. B., Aguiar, A. C., & Rostagno, M. A. (2021). Extraction of natural products
using supercritical uids and pressurized liquids assisted by ultrasound: Current
status and trends. Ultrasonics Sonochemistry, 74, Article 105584. https://doi.org/
10.1016/j.ultsonch.2021.105584
Dias, A. L. B., Arroio Sergio, C. S., Santos, P., Barbero, G. F., Rezende, C. A., &
Martínez, J. (2016). Effect of ultrasound on the supercritical CO
2
extraction of
bioactive compounds from dedo de moça pepper (Capsicum baccatum L. var.
pendulum). Ultrasonics Sonochemistry, 31, 284–294. https://doi.org/10.1016/j.
ultsonch.2016.01.013
Dias, A. L. B., Arroio Sergio, C. S., Santos, P., Barbero, G. F., Rezende, C. A., & Martínez,
J. (2017). Ultrasound-assisted extraction of bioactive compounds from dedo de moça
pepper (Capsicum baccatum L.): Effects on the vegetable matrix and mathematical
modeling. Journal of Food Engineering, 198, 36–44. https://doi.org/10.1016/j.
jfoodeng.2016.11.020 Chemistry, 281(25), 17359-17368. https://doi.org/10.1074/
jbc.M600861200.
Ding, M., Feng, R., Wang, S. Y., Bowman, L., Lu, Y., Qian, Y., … Shi, X. (2006). Cyanidin-
3-glucoside, a natural product derived from blackberry, exhibits chemopreventive
and chemotherapeutic activity. Journal of Biological Chemistry, 281(25),
17359–17368. https://doi.org/10.1074/jbc.M600861200
Du, F., Deng, B., Gao, L., Xiang, Y., & Zhang, J. (2013). Optimization of microwave-
assisted extraction technology of total avonoids from Malus micromalus Makino
using Ionic liquids and response surface methodology. Science and Technology of Food
Industry, 2013, 17.
Eisvand, F., Razavi, B. M., & Hosseinzadeh, H. (2020). The effects of Ginkgo biloba on
metabolic syndrome: A review. Phytotherapy Research, 34(8). https://doi.org/
10.1002/ptr.6646
Faria, E. L. P., Shabudin, S. V., Claúdio, A. F. M., V´
alega, M., Domingues, F. M. J.,
Freire, C. S. R., … Freire, M. G. (2017). Aqueous solutions of surface-active ionic
liquids: Remarkable alternative solvents to improve the solubility of triterpenic acids
and their extraction from biomass. ACS Sustainable Chemistry & Engineering, 5(8),
7344–7351. https://doi.org/10.1021/acssuschemeng.7b01616
Ferenczyova, K., Kalocayova, B., & Bartekova, M. (2020). Potential implications of
quercetin and its derivatives in cardioprotection. International Journal of Molecular
Sciences, 34(8), 1798–1811. https://doi.org/10.3390/ijms21051585
Ferrentino, G., Morozova, K., Mosibo, O. K., Ramezani, M., & Scampicchio, M. (2018).
Biorecovery of antioxidants from apple pomace by supercritical uid extraction.
Journal of Cleaner Production, 186, 253–261. https://doi.org/10.1016/j.
jclepro.2018.03.165
Flieger, J., & Flieger, M. (2020). Ionic liquids toxicity—Benets and threats. International
Journal of Molecular Sciences, 21(17), 6267. https://doi.org/10.3390/ijms21176267
Franquin-Trinquier, S., Maury, C., Baron, A., Le Meurlay, D., & Mehinagic, E. (2014).
Optimization of the extraction of apple monomeric phenolics based on response
surface methodology: Comparison of pressurized liquid-solid extraction and manual-
liquid extraction. Journal of Food Composition and Analysis, 34(1), 56–67. https://doi.
org/10.1016/j.jfca.2014.01.005
Fromm, M., Loos, H. M., Bayha, S., Carle, R., & Kammerer, D. R. (2013). Recovery and
characterisation of coloured phenolic preparations from apple seeds. Food Chemistry,
136(3–4), 1277–1287. https://doi.org/10.1016/j.foodchem.2012.09.042
Fu, L., Xu, B.-T., Xu, X.-R., Gan, R.-Y., Zhang, Y., Xia, E.-Q., & Li, H.-B. (2011).
Antioxidant capacities and total phenolic contents of 62 fruits. Food Chemistry, 129
(2), 345–350. https://doi.org/10.1016/j.foodchem.2011.04.079
Grigoras, C. G., Destandau, E., Foug`
ere, L., & Elfakir, C. (2013). Evaluation of apple
pomace extracts as a source of bioactive compounds. Industrial Crops and Products,
49, 794–804. https://doi.org/10.1016/j.indcrop.2013.06.026
Guo, X. F., Liu, J. P., Ma, S. Q., Zhang, P., & Sun, W. De. (2018). Avicularin reversed
multidrug-resistance in human gastric cancer through enhancing Bax and BOK
expressions. Biomedicine and Pharmacotherapy, 103, 67–74. https://doi.org/
10.1016/j.biopha.2018.03.110
Hajialyani, M., Farzaei, M. H., Echeverría, J., Nabavi, S. M., Uriarte, E., & Eduardo, S. S.
(2019). Hesperidin as a neuroprotective agent: A review of animal and clinical
evidence. Molecules, 24(3), 648. https://doi.org/10.3390/molecules24030648
Hameed, A., Hazur, R. M., Hussain, N., Raza, S. A., Rehman, M., Ashraf, S., …
Choudhary, M. I. (2018). Eriodictyol stimulates insulin secretion through cAMP/PKA
signaling pathway in mice islets. European Journal of Pharmacology, 820, 245–255.
https://doi.org/10.1016/j.ejphar.2017.12.015
Haminiuk, C. W. I., Maciel, G. M., Plata-Oviedo, M. S. V., & Peralta, R. M. (2012).
Phenolic compounds in fruits - an overview. International Journal of Food Science &
Technology, 47(10), 2023–2044. https://doi.org/10.1111/j.1365-2621.2012.03067.
x
Hansen, B. B., Spittle, S., Chen, B., Poe, D., Zhang, Y., Klein, J. M., … Doherty, B. W.
(2020). Deep eutectic solvents: A review of fundamentals and applications. Chemical
Reviews, 121, 1232–1285. https://doi.org/10.1021/acs.chemrev.0c00385
Hartogh, D. J. D., & Tsiani, E. (2019). Antidiabetic properties of naringenin: A citrus fruit
Polyphenol. Biomolecules, 9(3), 99. https://doi.org/10.3390/biom9030099
He, B., Zhang, L. L., Yue, X. Y., Liang, J., Jiang, J., Gao, X. L., & Yue, P. X. (2016).
Optimization of ultrasound-assisted extraction of phenolic compounds and
anthocyanins from blueberry (Vaccinium ashei) wine pomace. Food Chemistry, 204,
70–76. https://doi.org/10.1016/j.foodchem.2016.02.094
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
16
Hern´
andez-Carranza, P., ´
Avila-Sosa, R., Guerrero-Beltr´
an, J. A., Navarro-Cruz, A. R.,
Corona-Jim´
enez, E., & Ochoa-Velasco, C. E. (2016). Optimization of antioxidant
compounds extraction from fruit by-products: Apple pomace, orange and banana
peel. Journal of Food Processing and Preservation, 40(1), 103–115. https://doi.org/
10.1111/jfpp.12588
Hosseinzadeh, R., Khorsandi, K., & Hemmaty, S. (2013). Study of the effect of surfactants
on extraction and determination of polyphenolic compounds and antioxidant
capacity of fruits extracts. PloS One, 8(3), Article e57353. https://doi.org/10.1371/
journal.pone.0057353
Hyson, D. A. (2011). A comprehensive review of apples and apple components and their
relationship to human health. Advances in Nutrition, 2(5), 408–420. https://doi.org/
10.3945/an.111.000513
Illera, A. E., Chaple, S., Sanz, M. T., Ng, S., Lu, P., Jones, J., … Bourke, P. (2019). Effect
of cold plasma on polyphenol oxidase inactivation in cloudy apple juice and on the
quality parameters of the juice during storage. Food chemistry: X, 3, Article 100049.
https://doi.org/10.1016/j.fochx.2019.100049
Imran, M., Rauf, A., Abu-Izneid, T., Nadeem, M., Shariati, M. A., Khan, I. A., …
Mubarak, M. S. (2019). Luteolin, a avonoid, as an anticancer agent: A review.
Biomedicine and Pharmacotherapy, 12, Article 108612. https://doi.org/10.1016/j.
biopha.2019.108612
Jakobek, L., & Barron, A. R. (2016). Ancient apple varieties from Croatia as a source of
bioactive polyphenolic compounds. Journal of Food Composition and Analysis, 45,
9–15. https://doi.org/10.1016/j.jfca.2015.09.007
Jakobek, L., Boc, M., & Barron, A. R. (2015). Optimization of ultrasonic-assisted
extraction of phenolic compounds from apples. Food Analytical Methods, 8(10),
2612–2625. https://doi.org/10.1007/s12161-015-0161-3
Jeong, K. M., Zhao, J., Jin, Y., Heo, S. R., Han, S. Y., Yoo, D. E., & Lee, J. (2015). Highly
efcient extraction of anthocyanins from grape skin using deep eutectic solvents as
green and tunable media. Archives of Pharmacal Research, 38(12), 2143–2152.
https://doi.org/10.1007/s12272-015-0678-4
Krakowska, A., Ra´
nska, K., Walczak, J., & Buszewski, B. (2018). Enzyme-assisted
optimized supercritical uid extraction to improve Medicago sativa polyphenolics
isolation. Industrial Crops and Products, 124, 931–940. https://doi.org/10.1016/j.
indcrop.2018.08.004
Kumar, S., & Pandey, A. K. (2013). Chemistry and biological activities of avonoids: An
overview. The Scientic World Journal. https://doi.org/10.1155/2013/162750
Kumar, N., & Pruthi, V. (2014). Potential applications of ferulic acid from natural
sources. Biotechnology Reports, 4, 86–93. https://doi.org/10.1016/j.
btre.2014.09.002
Kumar, K., Srivastav, S., & Sharanagat, V. S. (2021). Ultrasound assisted extraction (UAE)
of bioactive compounds from fruit and vegetable processing by-products: A review.
Ultrasonics Sonochemistry, 70, Article 105325. https://doi.org/10.1016/j.
ultsonch.2020.105325
Lesjak, M., Beara, I., Simin, N., Pinta´
c, D., Majki´
c, T., Bekvalac, K., … Mimica-Duki´
c, N.
(2018). Antioxidant and anti-inammatory activities of quercetin and its derivatives.
Journal of Functional Foods, 40, 68–75. https://doi.org/10.1016/j.jff.2017.10.047
Li, H., Deng, Z., Wu, T., Liu, R., Loewen, S., & Tsao, R. (2012). Microwave-assisted
extraction of phenolics with maximal antioxidant activities in tomatoes. Food
Chemistry, 130(4), 928–936. https://doi.org/10.1016/j.foodchem.2011.08.019
Li, W., Shi, M., Wang, P., Guo, X., Li, C., & Kang, W. (2018). Efcient determination of
three avonoids in Malus pumila owers by ionic liquid-HPLC. Journal of Molecular
Liquids, 263, 139–146. https://doi.org/10.1016/j.molliq.2018.04.135
Li, Z., Meng, F., Zhang, Y., Sun, L., Yu, L., Zhang, Z., … Guo, J. (2016). Simultaneous
quantication of hyperin, reynoutrin and guaijaverin in mice plasma by LC-MS/MS:
Application to a pharmacokinetic study. Biomedical Chromatography, 30(7),
1124–1130. https://doi.org/10.1002/bmc.3660
Lima, ´
A. S., Soares, C. M. F., Paltram, R., Halbwirth, H., & Bica, K. (2017). Extraction and
consecutive purication of anthocyanins from grape pomace using ionic liquid
solutions. Fluid Phase Equilibria, 451, 68–78. https://doi.org/10.1016/j.
uid.2017.08.006
Lohani, U. C., & Muthukumarappan, K. (2016). Application of the pulsed electric eld to
release bound phenolics in sorghum our and apple pomace. Innovative Food Science
& Emerging Technologies, 35, 29–35. https://doi.org/10.1016/j.ifset.2016.03.012
Lu, Y., & Foo, L. Y. (1998). Constitution of some chemical components of apple seed.
Food chemistry, 61(1–2), 29–33. https://doi.org/10.1016/S0308-8146(97)00123-4
Macan, A. M., Kraljevi´
c, T. G., & Rai´
c-mali´
c, S. (2019). Therapeutic perspective of
vitamin C and its derivatives. Antioxidants, 8(8), 247. https://doi.org/10.3390/
antiox8080247
Machado, A. P. D. F., Pasquel-Re´
ategui, J. L., Barbero, G. F., & Martínez, J. (2015).
Pressurized liquid extraction of bioactive compounds from blackberry (Rubus
fruticosus L.) residues: A comparison with conventional methods. Food Research
International, 77, 675–683. https://doi.org/10.1016/j.foodres.2014.12.042
Makarova, E., G´
orna´
s, P., Konrade, I., Tirzite, D., Cirule, H., Gulbe, A., … Dambrova, M.
(2014). Acute anti-hyperglycaemic effects of an unripe apple preparation containing
phlorizin in healthy volunteers: A preliminary study. Journal of the Science of Food
and Agriculture, 95(3), 560–568. https://doi.org/10.1002/jsfa.6779
Malinowska, M., ´
Sliwa, K., Sikora, E., Ogonowski, J., Oszmia´
nski, J., & Kolniak-Ostek, J.
(2018). Ultrasound-assisted and micelle-mediated extraction as a method to isolate
valuable active compounds from apple pomace. Journal of Food Processing and
Preservation, 42(10), Article e13720. https://doi.org/10.1111/jfpp.13720
Martins Strieder, M., Neves, M. I. L., Silva, E. K., & Meireles, M. A. A. (2020). Low-
frequency and high-power ultrasound-assisted production of natural blue colorant
from the milk and unripe Genipa americana L. Ultrasonics Sonochemistry, 66, Article
105068. https://doi.org/10.1016/j.ultsonch.2020.105068
Massias, A., Boisard, S., Baccaunaud, M., Leal Calderon, F., & Subra-Paternault, P.
(2015). Recovery of phenolics from apple peels using CO
2
+ethanol extraction:
Kinetics and antioxidant activity of extracts. The Journal of Supercritical Fluids, 98,
172–182. https://doi.org/10.1016/j.supu.2014.12.007
Matsui, T. (2015). Condensed catechins and their potential health-benets. European
Journal of Pharmacology. https://doi.org/10.1016/j.ejphar.2015.09.017
Mihailovi´
c, N. R., Mihailovi´
c, V. B., Kreft, S., ´
Ciri´
c, A. R., Joksovi´
c, L. G., & Đurđevi´
c, P.
T. (2018). Analysis of phenolics in the peel and pulp of wild apples (Malus sylvestris
(L.) Mill.), 67, 1-9. Journal of Food Composition and Analysis. https://doi.org/
10.1016/j.jfca.2017.11.007.
Moreira, M. M., Barroso, M. F., Boeykens, A., Withouck, H., Morais, S., & Delerue-
Matos, C. (2017). Valorization of apple tree wood residues by polyphenols
extraction: Comparison between conventional and microwave-assisted extraction.
Industrial Crops and Products, 104, 210–220. https://doi.org/10.1016/j.
indcrop.2017.04.038
Mustafa, A., & Turner, C. (2011). Pressurized liquid extraction as a green approach in
food and herbal plants extraction: A review. Analytica Chimica Acta, 703(1), 8–18.
https://doi.org/10.1016/j.aca.2011.07.018
Naveed, M., Hejazi, V., Abbas, M., Kamboh, A. A., Khan, G. J., Shumzaid, M., …
XiaoHui, Z. (2018). Chlorogenic acid (CGA): A pharmacological review and call for
further research. Biomedicine and Pharmacotherapy, 97, 67–74. https://doi.org/
10.1016/j.biopha.2017.10.064
Panadare, D., Dialani, G., & Rathod, V. (2021). Extraction of volatile and non-volatile
components from custard apple seed powder using supercritical CO
2
extraction
system and its inventory analysis. Process Biochemistry, 100, 224–230. https://doi.
org/10.1016/j.procbio.2020.09.030
Pavli´
c, B., Naffati, A., Hojan, T., Vladi´
c, J., Zekovi´
c, Z., & Vidovi´
c, S. (2017). Microwave-
assisted extraction of wild apple fruit dust-production of polyphenol-rich extracts
from lter tea factory by-products. Journal of Food Process Engineering, 40(4), Article
e12508. https://doi.org/10.1111/jfpe.12508
Pei, K., Ou, J., Huang, J., & Ou, S. (2016). p-Coumaric acid and its conjugates: Dietary
sources, pharmacokinetic properties and biological activities. Journal of the Science of
Food and Agriculture, 96(9), 2952–2962. https://doi.org/10.1002/jsfa.7578
Pingret, D., Fabiano-Tixier, A. S., Bourvellec, C. Le, Renard, C. M. G. C., & Chemat, F.
(2012). Lab and pilot-scale ultrasound-assisted water extraction of polyphenols from
apple pomace. Journal of Food Engineering, 111(1), 73–81. https://doi.org/10.1016/
j.jfoodeng.2012.01.026
Ponte, L. G. S., Pavan, I. C. B., Mancini, M. C. S., da Silva, L. G. S., Morelli, A. P.,
Severino, M. B., … Simabuco, F. M. (2021). The hallmarks of avonoids in cancer.
Molecules, 26(7), 2029. https://doi.org/10.3390/molecules26072029
Rahath Kubra, I., Kumar, D., & Jagan Mohan Rao, L. (2016). Emerging trends in
microwave processing of spices and herbs. Critical Reviews in Food Science and
Nutrition, 56(13), 2160-2173. https://doi.org/10.1080/10408398.2013.818933.
Rajan, V. K., Shameera, S. A., Hasna, C. K., & Muraleedharan, K. (2018). A non toxic
natural food colorant and antioxidant ‘Peonidin’ as a pH indicator: A TDDFT
analysis. Computational Biology and Chemistry, 76, 202–209. https://doi.org/
10.1016/j.compbiolchem.2018.07.015
Ramirez, G., Zamilpa, A., Zavala, M., Perez, J., Morales, D., & Tortoriello, J. (2016).
Chrysoeriol and other polyphenols from Tecoma stans with lipase inhibitory activity.
Journal of Ethnopharmacology, 185, 1–8. https://doi.org/10.1016/j.jep.2016.03.014
Rana, S., Gupta, S., Rana, A., & Bhushan, S. (2015). Functional properties, phenolic
constituents and antioxidant potential of industrial apple pomace for utilization as
active food ingredient. Food Science and Human Wellness, 4(4), 180–187. https://doi.
org/10.1016/j.fshw.2015.10.001
Reis, S. F., Rai, D. K., & Abu-Ghannam, N. (2012). Water at room temperature as a
solvent for the extraction of apple pomace phenolic compounds. Food Chemistry, 135
(3), 1991–1998. https://doi.org/10.1016/j.foodchem.2012.06.068
Rezaei, S., Rezaei, K., Haghighi, M., & Labba, M. (2013). Solvent and solvent to sample
ratio as main parameters in the microwave-assisted extraction of polyphenolic
compounds from apple pomace. Food Science and Biotechnology, 22(5), 1–6. https://
doi.org/10.1007/s10068-013-0212-8
Rostagno, M. A., D’Arrigo, M., Martínez, J. A., & Martínez, J. A. (2010). Combinatory
and hyphenated sample preparation for the determination of bioactive compounds
in foods. TrAC - Trends in Analytical Chemistry, 29(6), 553–561. https://doi.org/
10.1016/j.trac.2010.02.015
Rostagno, M. A., & Prado, J. M. (2013). Natural product extraction: principles and
applications. Royal Society of Chemistry.
Salehi, B., Venditti, A., Shari-Rad, M., Kręgiel, D., Shari-Rad, J., Durazzo, A., …
Martins, N. (2019). The therapeutic potential of Apigenin. International Journal of
Molecular Sciences, 20(6), 1305. https://doi.org/10.3390/ijms20061305
Santos, P., Aguiar, A. C., Barbero, G. F., Rezende, C. a, & Martínez, J. (2015).
Supercritical carbon dioxide extraction of capsaicinoids from malagueta pepper
(Capsicum frutescens L.) assisted by ultrasound. Ultrasonics Sonochemistry, 22,
78–88. https://doi.org/10.1016/j.ultsonch.2014.05.001.
Santos, M. P., Souza, M. C., Sumere, B. R., da Silva, L. C., Cunha, D. T., Bezerra, R. M. N.,
& Rostagno, M. A. (2019). Extraction of bioactive compounds from pomegranate
peel (Punica granatum L.) with pressurized liquids assisted by ultrasound combined
with an expansion gas. Ultrasonics Sonochemistry, 54, 11–17. https://doi.org/
10.1016/j.ultsonch.2019.02.021
Sato, Y., Itagaki, S., Kurokawa, T., Ogura, J., Kobayashi, M., Hirano, T., … Iseki, K.
(2011). In vitro and in vivo antioxidant properties of chlorogenic acid and caffeic
acid. International Journal of Pharmaceutics, 403(1–2), 136–138. https://doi.org/
10.1016/j.ijpharm.2010.09.035
Sharma, S., Kori, S., & Parmar, A. (2015). Surfactant mediated extraction of total
phenolic contents (TPC) and antioxidants from fruits juices. Food Chemistry, 185,
284–288. https://doi.org/10.1016/j.foodchem.2015.03.106
Shay, J., Elbaz, H. A., Lee, I., Zielske, S. P., Malek, M. H., & Hüttemann, M. (2015).
Molecular mechanisms and therapeutic effects of (-)-epicatechin and other
L.C. da Silva et al.
Food Chemistry: X 12 (2021) 100133
17
polyphenols in cancer, inammation, diabetes, and neurodegeneration. Oxidative
Medicine and Cellular Longevity, 2015, 1–13. https://doi.org/10.1155/2015/181260
Silva, F. A., Carmo, R. M. C., Fernandes, A. P. M., Kholany, M., Coutinho, J. A. P., &
Ventura, S. P. M. (2017). Using ionic liquids to tune the performance of aqueous
biphasic systems based on pluronic L-35 for the purication of naringin and rutin.
ACS Sustainable Chemistry & Engineering, 5(8), 6409–6419. https://doi.org/10.1021/
acssuschemeng.7b00178
Skrypnik, L., & Novikova, A. (2020). Response surface modeling and optimization of
polyphenols extraction from apple pomace based on nonionic emulsiers. Agronomy,
10(1), 92. https://doi.org/10.3390/agronomy10010092
Souza Mesquita, L. M., Martins, M., Pisani, L. P., Ventura, S. P. M., & de Rosso, V. V.
(2021). Insights on the use of alternative solvents and technologies to recover bio-
based food pigments. Comprehensive Reviews in Food Science and Food Safety, 20,
787-818. https://doi.org/https://doi.org/10.1111/1541-4337.12685.
Souza Mesquita, L. M., Martins, M., Maricato, ´
E., Nunes, C., Quinteiro, P. S. G. N.,
Dias, A. C. R. V., … Ventura, S. P. M. (2020). Ionic liquid-mediated recovery of
carotenoids from the Bactris gasipaes fruit waste and their application in food-
packaging chitosan lms. ACS Sustainable Chemistry & Engineering, 8(10),
4085–4095. https://doi.org/10.1021/acssuschemeng.9b06424
Souza Mesquita, L. M., Ventura, S. P. M., Braga, A. R. C., Pisani, L. P., Dias, A., & de
Rosso, V. V. (2019). Ionic liquid-high performance extractive approach to recover
carotenoids from Bactris gasipaes fruits. Green Chemistry, 21, 2380–2391. https://
doi.org/10.1039/C8GC03283A
Souza, M. C., Santos, M. P., Sumere, B. R., Silva, L. C., Cunha, D. T., Martínez, J., …
Rostagno, M. A. (2020). Isolation of gallic acid, caffeine and avonols from black tea
by on-line coupling of pressurized liquid extraction with an adsorbent for the
production of functional bakery products. Lwt, 117, Article 108661. https://doi.org/
10.1016/j.lwt.2019.108661
Srinivasulu, C., Ramgopal, M., Ramanjaneyulu, G., Anuradha, C. M., & Suresh Kumar, C.
(2018). Syringic acid (SA) – A review of its occurrence, biosynthesis,
pharmacological and industrial importance. Biomedicine and Pharmacotherapy, 108,
547–557. https://doi.org/10.1016/j.biopha.2018.09.069
Sumere, B. R., de Souza, M. C., dos Santos, M. P., Bezerra, R. M. N., da Cunha, D. T.,
Martinez, J., & Rostagno, M. A. (2018). Combining pressurized liquids with
ultrasound to improve the extraction of phenolic compounds from pomegranate peel
(Punica granatum L.). Ultrasonics Sonochemistry, 48, 151–162. https://doi.org/
10.1016/j.ultsonch.2018.05.028
Ullah, R., Ikram, M., Park, T. J., Ahmad, R., Saeed, K., Alam, S. I., … Kim, M. O. (2020).
Vanillic acid, a bioactive phenolic compound, counteracts LPS-induced neurotoxicity
by regulating c-Jun N-Terminal kinase in mouse brain. International Journal of
Molecular Sciences, 22(1), 361. https://doi.org/10.3390/ijms22010361
Ventura, S. P. M., E Silva, F. A., Quental, M. V., Mondal, D., Freire, M. G., & Coutinho, J.
A. P. (2017). Ionic-liquid-mediated extraction and separation processes for bioactive
compounds: past, present, and future trends. Chemical Reviews, 117(10),
6984–7052. https://doi.org/10.1021/acs.chemrev.6b00550.
Vigan´
o, J., Aguiar, A. C., Moraes, D. R., Jara, J. L. P., Eberlin, M. N., Cazarin, C. B. B., …
Martínez, J. (2016). Sequential high pressure extractions applied to recover
piceatannol and scirpusin B from passion fruit bagasse. Food Research International,
85, 51–58. https://doi.org/10.1016/j.foodres.2016.04.015
Vigan´
o, J., Assis, B. F. de P., N´
athia-Neves, G., dos Santos, P., Meireles, M. A. A., Veggi, P.
C., & Martínez, J. (2020). Extraction of bioactive compounds from defatted passion
fruit bagasse (Passiora edulis sp.) applying pressurized liquids assisted by
ultrasound. Ultrasonics Sonochemistry, 64, 104999. https://doi.org/10.1016/j.
ultsonch.2020.104999.
Vigan´
o, J., Zabot, G. L., & Martínez, J. (2017). Supercritical uid and pressurized liquid
extractions of phytonutrients from passion fruit by-products: Economic evaluation of
sequential multi-stage and single-stage processes. The Journal of Supercritical Fluids,
122, 88–98. https://doi.org/10.1016/j.supu.2016.12.006
Wang, L., Boussetta, N., Lebovka, N., & Vorobiev, E. (2018). Selectivity of ultrasound-
assisted aqueous extraction of valuable compounds from esh and peel of apple
tissues. LWT, 93, 511–516. https://doi.org/10.1016/j.lwt.2018.04.007
Wang, L., Boussetta, N., Lebovka, N., & Vorobiev, E. (2019). Ultrasound assisted
purication of polyphenols of apple skins by adsorption/desorption procedure.
Ultrasonics Sonochemistry, 55, 18–24. https://doi.org/10.1016/j.
ultsonch.2019.03.002
Wang, X., Yang, Y., An, Y., & Fang, G. (2019). The mechanism of anticancer action and
potential clinical use of kaempferol in the treatment of breast cancer. Biomedicine
and Pharmacotherapy, 117, Article 109086. https://doi.org/10.1016/j.
biopha.2019.109086
Wijngaard, H., & Brunton, N. (2009). The optimization of extraction of antioxidants from
apple pomace by pressurized liquids. Journal of Agricultural and Food Chemistry, 57
(22), 10625–10631. https://doi.org/10.1021/jf902498y
Wikiera, A., Mika, M., & Grabacka, M. (2015). Multicatalytic enzyme preparations as
effective alternative to acid in pectin extraction. Food Hydrocolloids, 44, 156–161.
https://doi.org/10.1016/j.foodhyd.2014.09.018
Wiktor, A., Sledz, M., Nowacka, M., Rybak, K., & Witrowa-Rajchert, D. (2016). The
inuence of immersion and contact ultrasound treatment on selected properties of
the apple tissue. Applied Acoustics, 103, 136–142. https://doi.org/10.1016/j.
apacoust.2015.05.001
Withouck, H., Boeykens, A., Vanden Broucke, M., Moreira, M. M., Delerue-Matos, C., &
De Cooman, L. (2019). Evaluation of the impact of pre-treatment and extraction
conditions on the polyphenolic prole and antioxidant activity of Belgium apple
wood. European Food Research and Technology, 245(11), 2565–2578. https://doi.org/
10.1007/s00217-019-03373-2
Xu, Y., Fan, M., Ran, J., Zhang, T., Sun, H., Dong, M., … Zheng, H. (2016). Variation in
phenolic compounds and antioxidant activity in apple seeds of seven cultivars. Saudi
Journal of Biological Sciences, 23(3), 379–388. https://doi.org/10.1016/j.
sjbs.2015.04.002
Xu, D. P., Li, Y., Meng, X., Zhou, T., Zhou, Y., Zheng, J., … Li, H. Bin (2017). Natural
antioxidants in foods and medicinal plants: Extraction, assessment and resources.
International Journal of Molecular Sciences, 18(1), 96. https://doi.org/10.3390/
ijms18010096
Yue, T., Shao, D., Yuan, Y., Wang, Z., & Qiang, C. (2012). Ultrasound-assisted extraction,
HPLC analysis, and antioxidant activity of polyphenols from unripe apple. Journal of
Separation Science, 35(16), 2138–2145. https://doi.org/10.1002/jssc.201200295
L.C. da Silva et al.
