Food Bioscience 35 (2020) 100547

Contents lists available at ScienceDirect

Food Bioscience
journal homepage: www.elsevier.com/locate/fbio

The effects of ultrasound assisted extraction on yield, antioxidant, T

anticancer and antimicrobial activity of polyphenol extracts: A review
Courage Sedem Dzaha,b, Yuqing Duana,∗, Haihui Zhanga, Chaoting Wena, Jixian Zhanga,
Guangying Chenc, Haile Maa
a
Department of Food Science and Engineering, School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu, 212013, China
b
Department of Food Science and Technology, Faculty of Applied Sciences and Technology, Ho Technical University, Ho, Volta Region, HP217, Ghana
c
Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, Hainan Normal University, Haikou, Hainan, 571158, China

A R T I C LE I N FO A B S T R A C T

Keywords: Ultrasound assisted extraction (UAE) is widely used in recent times for its benefits, but it is difficult to find
Ultrasound assisted extraction literature that comprehensively addresses the effect of UAE-specific parameters such as temperature, frequency,
Polyphenols power, solvent type, and solvent to material ratio on extracted compounds and their functionality. There is no
Extraction conditions review done so far on the effects of all UAE parameters on polyphenol extracts to guide the design of extraction
Biological activity
protocols. This review therefore focuses on the effects of UAE parameters on the yield and composition, as well
Antioxidants
as the effects of the UAE on the antioxidant, anticancer, and antimicrobial properties of phenolic extracts. Higher
extraction temperatures above 50 °C are degradative to polyphenols in extracts; lower frequencies within the
power ultrasound range below 40 kHz are most effective; polyphenol yield generally increases with increasing
power, but with a threshold, beyond which no significant increase is observed; and higher ultrasound power
produces free hydroxyl radicals which degrade polyphenols, especially in the presence of high water content. A
comparative assessment of literature showed that, UAE does not only contribute to increased extraction yield of
polyphenols, but also better preserves and increases the biological activity of polyphenol extracts compared to
traditional maceration and Soxhlet extraction. A full picture of UAE is given to serve as a reference material on
the control of UAE parameters for desired results and efficiency.

1. Introduction
Phenolic compounds are secondary metabolites, common in the
forms of phenolic acids and flavonoids in plants (Dzah, 2014;
Ghasemzadeh & Ghasemzadeh, 2011; Lin et al., 2016). They are the
most abundant of many phytochemicals and have been given enormous
attention due to their healthful benefits (Huang, Yin, & Chiu, 2011; Li
et al., 2014; Mozaffarian, 2017; Scalbert, Manach, Morand, & Remesy,
2005; Schönfeldt, Hall, & Pretorius, 2018; Smethers & Rolls, 2018).
These health benefits have been associated with their antioxidative,
anti-inflammatory, anticancer, and antimicrobial properties (Appleton
et al., 2011; Carvalho et al., 2017; Evans, Kawabata, & Thomas, 2014;
Flores, Wu, Negrin, & Kennelly, 2015; Manganaris, Goulas, Vicente, &
Terry, 2014; Zielinski et al., 2014). The advantages derived from their
use and the increased research interest have led to the development of
several advanced technologies that can permit their extraction without
largely compromising their biological activities (Ameer, Shahbaz, &
Kwon, 2017; Dent et al., 2015; Falleh, Ksouri, Lucchessi, Abdelly, &
Magné, 2012; Ma et al., 2008; Sevenich & Mathys, 2018; Wen et al.,
2018; Wizi et al., 2018). One of such technologies which has shown
substantial advantage over traditional maceration and Soxhlet extrac-
tions is the use of ultrasound assisted extraction (UAE) (Luo et al., 2018;
Rodsamran & Sothornvit, 2019; Wen et al., 2018; Yolmeh, Habibi-
Najafi, & Farhoosh, 2014). However, the successful application and
efficiency of these technologies, including UAE, is met with the chal-
lenge of process optimization. The ability to optimize UAE of poly-
phenols prevents material and solvent wastage and as well ensures in-
creased extraction yield and preservation of biological properties of
extracts. An understanding of how UAE parameters such as time, fre-
quency, power, temperature, and solvent to material ratio influence the
treatment outcomes and efficiency, is therefore important to the success
of polyphenol extraction, hence the need for this study. Also, no such
comprehensive literature dedicated to the effects of UAE on the yield,
composition and biological properties of polyphenols was found. This
study therefore serves as a relevant reference for current and future
UAE designs. Published journals papers relating to the use of UAE in the

∗
Corresponding author. School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu, 212013, China.
E-mail address: dyq101@ujs.edu.cn (Y. Duan).

https://doi.org/10.1016/j.fbio.2020.100547
Received 12 June 2019; Received in revised form 24 February 2020; Accepted 24 February 2020
Available online 28 February 2020
2212-4292/ © 2020 Elsevier Ltd. All rights reserved.
C.S. Dzah, et al.
extraction of polyphenols were screened from academic databases (such
as Web of Science and Science Direct) based on results that specifically
showed improvements in extraction and biological activity of extracts
as well as UAE-specific parameter effects.
2. Types of ultrasound assisted extraction technology
The identification of differences among the various machinery used
in UAE depends largely on the make of the equipment and the varia-
tions in the controls of microenvironment parameters such as tem-
perature, frequency, power, and time. Some criteria used in their
classification are described based on interaction between ultrasound
source and extraction medium, frequency ranges, frequency combina-
tions, and purpose.
2.1. Interaction between ultrasound source and extraction medium
A criterion used to classify this technology is whether or not there is
a direct interaction between the extraction medium and the ultrasound
source. When the source is in direct contact with the extraction
medium, it is termed direct ultrasonication and the vice versa is true
with indirect ultrasonication (Fig. 1). It is established by studies that
direct contact between sound waves and extraction medium allows
better interaction and enhances higher and more intense cavitation
effects which improves extraction of target compounds from cellular
plant matrices than seen in indirect ultrasonication such as the ultra-
sound bath. Mellado, Figueroa, Baez, Meléndrez, and Fernández (2019)
investigated the effects of probe and bath ultrasonic treatments on
graphene oxide (GO) structure and observed that probe sonication in-
duced deformities in the GO layers, degrading their properties, whereas
bath sonication was less invasive and caused less damage to the GO
sheet structure. Depending on the purpose of ultrasound treatment, it is
important to understand the differences in their mechanism of action
and effects on materials. However, there is the potential of the probe or
horn carrying over residues from previous extractions that may con-
taminate subsequent processes (Mirza et al., 2008). As well, there is a
high likelihood of having the probe or horn changed over time due to
potential corrosion as a result of chemical oxidative reactions between
probe materials and extraction medium components. For indirect ul-
trasonication (Fig. 2), it is shown that as sound waves pass through two
media (water bath and sample container) before getting to the extrac-
tion medium, intensity reduces with concomitant reduction in cavita-
tion intensity and extraction rate, compared to direct ultrasonication.
Beside the relatively lower extraction rate, its advantage is the absence
of cross contamination from previous extraction procedures, unlike
Fig. 1. Different types of direct ultrasonication equipment. (a) shows an equipment with a water bath which contains sample held in a second vessel. (b) shows an
equipment with no water bath, but a jacketed glass beaker which holds sample in extraction medium.
2
Food Bioscience 35 (2020) 100547
observed for direct ultrasonication.
2.2. Frequency range
Differences are also found between ultrasonication equipment re-
garding the range of sound frequencies allowable by design (Zhang
et al., 2017). There are different ranges such as power ultrasound
(20 kHz–100 kHz), mostly applied in cleaning, plastic welding and
sonochemistry (including extraction protocols); the extended range
(100 kHz–2 MHz), also mostly used in sonochemistry; and high fre-
quency range (2 MHz–10 MHz), often used in medical imaging (Varray
et al., 2012). Most often the power ultrasound range is used in the
extraction of biologically active compounds from biological matrices,
such as in the extraction of polyphenols from plant and waste food
materials. Most of the ultrasonic probes or cleaning baths available in
commercial quantities work at low ultrasound frequencies (20–40 kHz).
Low frequencies have been observed to generate large cavitation bub-
bles in extraction solvents which implode violently, generating high
shear whiles creating microjets that ensure higher cellular degradation,
increased solvent penetration and higher extraction rate). Bhangu,
Ashokkumar, and Lee (2016) also showed that although low ultrasound
frequency seems optimal to generate higher nucleation and fragmen-
tation rates, the exact optimal frequency is probably reactor and system
specific, hence the need to design optimization tests that are specific to
different extractions and setups.
2.3. Frequency combinations
Certain ultrasound applications use frequencies in different combi-
nations, whether it is a combination of sound waves of the same fre-
quency or of varying frequencies (Yang et al., 2017; Zhang et al., 2017).
Some studies have shown that ultrasonication can be mono or multi-
frequency-based and the results vary. As cavitation effect is modulated
by frequency types applied, it is seen that understanding how to use
frequencies in combination has a great potential to improve extraction
yield (Leighton, 1995; Tatake & Pandit, 2002; Zhang et al., 2017). Ul-
trasound sources such as probes or horns are designed to either emit
single or dual or other multiple frequencies. A modelling and experi-
mental study was done by Tatake and Pandit (2002) to understand the
effect of dual frequency ultrasound source on cavity dynamics and ca-
vitation yield. In their study, the effects of the introduction of a second
wave were compared to those of a conventional single wave process
and results showed that the introduction of a second sound wave in-
creased the distribution of the cavitation activity and resulted in uni-
form yields. The formation of standing waves was also minimized, and
C.S. Dzah, et al.
Fig. 2. An ultrasound water bath. Ultrasound is produced within the equipment and sound waves travel through the water and glassware into extraction mixture
(Source: Laboratory, Jiangsu University, Food Science and Engineering department).
reactant volume and dissipated sound energy were more effectively
used, resulting in a two-fold energy efficiency compared to that from
the single sound wave. An extension of this experiment also measured
variations in efficiency with the use of sound waves of the same or
different frequencies, and it was suggested that sound waves introduced
should be of the same frequency with respect to the initial, as this was
shown to increase cavitation effects with higher chemical yields
(Santos, Guzmán, Espinosa, & Estrada, 2016; Tatake & Pandit, 2002).
This observation seems to be true, cutting across other applications
such as in medical imaging technology as reported by Varray et al.
(2012). Another study by Liu and Hsieh (2009) confirmed the ad-
vantage of using multiple-frequency over single-frequency ultrasound
in effectively enhancing the acoustic cavitation effect during sample
treatments in the pharmaceutical industry. The results of the study
showed that dual-frequency ultrasound treatment has a greater poten-
tial to increase acoustic cavitation and can generate bubbles at an in-
creased rate up to 5 times higher than observed with single-frequency
treatment.
2.4. Frequency and power combinations
Ultrasonic techniques can also be classified into different groups
depending on the ranges of frequency and power during operation and
their combinations. Diagnostic and high frequency ultrasound is char-
acterized with high frequency and low power, whereas that of low
frequency and high power is classified as power ultrasound (Juliano
et al., 2017). It is worth noting that diagnostic ultrasound uses higher
frequencies than those normally classified as high frequency ultra-
sound. The latter is known to produce low cavitation effects in ex-
traction materials or mixtures but has been observed to enhance se-
paration of particulates from biological matrices (Bhangu et al., 2016;
Juliano et al., 2017). Diagnostic ultrasound is commonly used medi-
cally to measure the state of internal tissue structures with low power
(< 100 mWcm−2), and high frequency (1–10 MHz). The power used in
this technique is low enough to not give any physicochemical changes
to the tissues of interest (Frizzell, 1988).
High frequency, low power ultrasound has been used in food ap-
plications to produce standing waves called megasonics; useful in the
extraction of oil from the olives. Its application increased the ex-
tractability of oil from olive fruits (Juliano et al., 2017). Although re-
commended for oil extraction due to increased extractability, high
frequency ultrasound negatively influenced anthocyanins and phenolics
in extracts, as well as antioxidant activity in berry extracts (Stojanovic
& Silva, 2007). This can be explained by the fact that high ultrasound
frequencies generate high amounts of free radicals that degrade phenols
and reduce their antioxidant properties (Crum, 1995; Masuda,
Maruyama, Eguchi, Hirakawa, & Murakami, 2015; Miljevic et al.,
2014). Usually, frequencies used range between 100 kHz and 1 MHz,
significantly lower than applied in diagnostic ultrasound. This tech-
nique also does not induce any changes in materials due to the low
power or intensities used, and several examples of its successful ap-
plication are observed in the food industry such as its use in fats and oils
characterization studies (McClements & Povey, 1992); emulsions
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Food Bioscience 35 (2020) 100547
(Coupland & McClements, 2001; McClements, 1991); and crystal-
lization of carbohydrates (Gülseren & Coupland, 2008; Yucel &
Coupland, 2010, 2011a, b). With such high frequencies coupled with
low powers, the treatments have been shown to be non-invasive and
nondestructive, making it one of the best means of studying samples
that need to be kept intact.
3. Effects of ultrasound microenvironment parameters
The polyphenol composition of extracts from plant sources differ
from plant to plant, based on several influencing factors from both
biotic and abiotic environmental conditions. Polyphenols play major
functions in plant defense mechanisms against predators, auto-oxida-
tive effects, induced oxidative stress, drought stress, infections, and
extreme weather conditions among others (Vladimir-Knežević et al.,
2012). They are also useful in signaling pathway modulation, anti-
oxidation reactions, conservation of enzyme moieties, attraction of
pollinators, development of flavor compounds, and cell membrane in-
tegrity preservation (Moosavi, Hosseini, Saso, & Firuzi, 2016). Beside
these primary reasons given for the varied polyphenol composition in
plants, the extraction techniques, solvents used and other parameters
during their separation from complex plant matrixes have the potential
to also alter the composition of extracts (Altemimi, Watson, Choudhary,
Dasari, & Lightfoot, 2016; Do et al., 2014; Turkmen, Sari, & Velioglu,
2006). Most often, studies done on the effects of extraction methods on
biochemical properties of extracts consider the effects of extraction
microenvironment conditions such as temperature, solvent to material
ratio, and time (Li et al., 2016; Maran et al., 2017; Zhong & Wang,
2010). For UAE, additional conditions such as frequency, intensity, and
power are also studied (Wen et al., 2018).
3.1. Effects of extraction temperature
Many single-factor UAE experiments have been done and have
confirmed the effects of extraction temperature on polyphenol yield.
Maran et al. (2017) studied the effect of extraction temperature among
other parameters on anthocyanin, flavonoid and total phenolic contents
of Nephelium lappaceum peel extracts obtained using UAE. Results
showed that yield was increased due to increased material porosity,
higher solvation and mass transfer when extraction temperature in-
creased (Maran et al., 2017). This was confirmed by others who ob-
served similar increments in extraction yield of phenolic components of
samples as a result of increased extraction temperature (Altemimi et al.,
2016; Li et al., 2016; Toma, Vinatoru, Paniwnyk, & Mason, 2001).
Added, increased temperature also reduces surface tension and visc-
osity in extracts, which also enhances extraction yield. Dai and Mumper
(2010) observed that viscosity and surface tension of solvents-sample
mixtures are decreased at higher temperatures, increasing matrix pe-
netration and extraction rate of polyphenols.
Despite the advantages, many phenolic compounds are easily hy-
drolyzed and oxidized at higher temperatures, especially when ex-
tracted over extended periods (Bi, Yang, Sun, Chen, & Zhang, 2011; Dai
& Mumper, 2010). Akowuah, Mariam, and Chin (2009) showed that
C.S. Dzah, et al.
total phenolic content in extracts decreased with extraction tempera-
tures exceeding 60 °C due to oxidative degradation. The sensitivity of
polyphenols to elevated temperatures was also shown about three
decades ago by Havlikova and Mikova (1985). They showed that long
extraction times at high temperatures increased the rate of phenol
oxidation and decreased the yield of total phenolic compounds in ex-
tracts. For example, orthodox polyphenol extraction (such as macera-
tion) is typically done at temperatures between 20 and 50 °C, and not at
temperatures above this range (Jackman, Yada, Tung, & Speers, 1987).
Temperatures above 70 °C especially have been shown to lead to rapid
polyphenol degradation, hence the need to select efficient extraction
temperatures that maintain the stability of phenolic compounds
(Havlikova & Mikova, 1985). It is also important to mention that the
sensitivity of a sample to temperature-induced polyphenol degradation
depends on the types of polyphenol compounds available in the extract
or plant matrix, and their physicochemical and biochemical char-
acteristics, as well as solvent-sample interaction.
3.2. Effects of ultrasonic power
Increased cavitation effect attributed to increased ultrasound power
has been reported to have increased polyphenol yield in Nephelium
lappaceum fruit peel extract (Maran et al., 2017) and grape seeds when
power was increased from 50 to 150 W (Da Porto, Porretto, & Decorti,
2013). Different ultrasound power intensities were used in extracting
polyphenols from mashed tea leaves and yield increased by 16.6%
when power increased from 25 to 125 W (Van Man, Anh Vu, & Chi Hai,
2017). Polyphenol yield of Acer truncatum leaves extracts increased by
9.5% when power was increased from 150 to 240 W. Beside the in-
creased extraction of polyphenols, it was observed that hydroxyl radi-
cals (OH*) could be produced at high ultrasonic power that would react
with phenolic compounds and degrade them, especially in the presence
of high-water content (Fernando and Soysa, 2015; Phan, Nguyen, & Le,
2012). Caution must therefore be taken to avoid high power-induced
polyphenol degradation.
Changes in chemical composition of extracts have also been ob-
served in other studies regarding the effect of high ultrasound power. In
oenology studies, high power ultrasound (HPU) was used in the treat-
ment of must to increase diffusion of favorable compounds during
fermentation. It was observed that the chemical composition of poly-
phenols was significantly changed. Significant decreases in total poly-
phenols and total anthocyanins were also observed with high ultra-
sound power (Ćurko et al., 2017).
3.3. Effects of ultrasonic frequency
The frequency applied during UAE procedures was shown to be
directly linked to the polyphenols and flavonoids compositions in ex-
tracts (Carciochi, Manrique, & Dimitrov, 2015). According to some
studies, increasing ultrasonic frequency within the power ultrasonic
range (20–100 kHz) led to increased polyphenol yields (Paini et al.,
2015). Bhangu et al. (2016) also showed that low frequencies increased
acoustic cavitation, which accounted for significant physicochemical
changes in materials. Total phenolic contents and free radical scaven-
ging properties of peach and pumpkins were best at a frequency of
37 kHz (Altemimi et al., 2016). On the other hand, the generation of
standing waves (megasonics) at high frequency had no significant im-
provement on the quality and chemical composition of olive oil
(Juliano et al., 2017).
Unfortunately, and similar to the effects of high ultrasound power,
high frequency ultrasound has also been reported to generate high
amounts of free radicals which degrade polyphenols and reduce their
biological activity (Fernando and Soysa, 2015; Phan et al., 2012). This
was attributed to the formation of unstable bubbles, leading to transient
cavitation. These unstable bubbles collapse and generate hydrogen
atoms (H) and hydroxyl radicals (OH*) in aqueous solutions, which are
4
Food Bioscience 35 (2020) 100547
likely to mediate solvent and solute decomposition, polymerization and
degradation of polyphenols (Masuda et al., 2015; Riesz, BerdahI, &
Christman, 1985). It is therefore important that the type and physico-
chemical nature of material to be extracted is carefully considered,
especially when using water as the sole extraction solvent so as to im-
prove yield without compromising the biological activity of poly-
phenols.
3.4. Effects of extraction solvent
The selection of an appropriate solvent for UAE depends on polarity,
melting point, boiling point, density, specific gravity, affinity for target
component, as well as effect on purity and activity of extracted com-
pound (Zou et al., 2014). Another factor to consider is the extraction
parameters to use and their suitability for the solvent, intermediate and
final reaction products, and how the solvent may react with target
compounds with extraction conditions. The biochemical and physico-
chemical properties of extraction solvents used for UAE are important
because they define the nature of the extraction medium and interact
with treated material and extracted compounds. Potential changes that
may occur in extraction solvents may have significant effects on the
stability of polyphenols and efficiency of treatments.
Often, during UAE, solvents used for the extraction of bioactive
plant compounds are a mixture, comprising of both organic and aqu-
eous phases in different ratios (Vankar & Srivastava, 2010). Organic
solvents such as ethanol, methanol, acetone and isopropanol, mixed
with varying proportions of water, have been widely used to extract
polyphenols and antioxidant compounds from plant sources using UAE.
On some occasions, 100% of either organic solvent or water is used for
extraction. Also, in some studies, extraction solvents have been acid-
ified to preserve sensitive polyphenols from oxidative degradation
(Dzah, 2014). The principle behind this is that, acids produce hydrogen
ions (H+) that stabilize free radicals that may be produced during ul-
trasonication. One factor that determines the ratios of the solvent
mixtures is the affinity of target compounds for the solvents. If a target
compound is more polar, the proportion of the polar fraction (water)
exceeds that of the non-polar solvent, and vice versa. In a study done by
Falleh et al. (2012), methanol and ethanol were used exclusively to
extract polyphenols from Mesembryanthemum edule L. Aizoaceae shoots.
Results showed that the methanolic extract had significantly higher
total polyphenol contents than the ethanolic extract, but the anti-
oxidant activity obtained for the latter was significantly higher (Falleh
et al., 2012). This could be explained by the possibility that different
types of polyphenols were extracted in the different solvents, probably
due to affinity differences.
Another study done by Xu et al. used ethanol at concentrations
ranging from 10 to 90% with fixed UAE conditions. The observed total
antioxidant activities of extracts significantly increased by 28.2% when
ethanol concentration was increased from 10 to 50%, and significantly
dropped when ethanol concentration was further increased from 50 to
90%. Other studies done using ethanol confirmed that using a con-
centration of 50% gave the best antioxidant yields from Zizyphus lotus
fruits (Hammi, Jdey, Abdelly, Majdoub, & Ksouri, 2015). Um, Han, and
Lee (2017) also extracted polyphenols from Rosa rugosa fruits using
UAE at 50 °C for 30 min in 50% ethanol and results showed higher
antioxidant activity of extracts. Similar results were obtained using
ethanol at concentrations close to 50% (Lu et al. (2015), Cryptotaenia
japonica, 55%; Rodsamran and Sothornvit (2019), lime peel, 55%;
Zhou, Xu, et al. (2017) and Zhou, Zheng, et al. (2017), Melastoma
sanguineum, 42.9%).
3.5. Effects of solvent to material ratio
As discussed earlier in section 3.4, the characteristics of solvents in
relation to treated materials, their affinities for each other, their pro-
portions, and extraction conditions are important parameters to
C.S. Dzah, et al.
consider. Knowing the optimum amount of solvent to be used is of
economic relevance, as well as important for enhancing extraction
outcomes and efficiency. Several studies have been done with different
combinations of extraction solvents and plant materials (solvent to
material ratio), and have shown varied results. For example, optimi-
zation of UAE of rice grain phenolics using two solvent to material
ratios (2.5:1 and 5:1) showed that the 5:1 ratio gave the best yield of
polyphenols (Setyaningsih, Saputro, Carrera, & Palma, 2019). Other
studies also confirmed this observation for increased polyphenol yield
(Oliveira et al. (2019), Hydrocotyle umbellate, 5:1; Pinela et al. (2019),
Hibiscus sabdariffa calyces, 33.3:1) and antioxidant activity, Jatropha
integerrima, 40:1).
The effect of solvent to material ratio can be attributed to the pos-
sibility that the reduced mixture density attained as a result of higher
solvent to material ratio increases ultrasound wave propagation speed
(v), reducing the effect of attenuation of ultrasound power (P) and in-
creasing the transfer of energy (E)/distance covered (d) by wave/time
(t), which can be established using the equation:
P = K ⎛Ϩ [(E ∗ v )/ d]……where Ϩ is material stiffness
ρ⎞
⎝ ⎠
This efficient transfer of energy as a result of reduced mixture
density increases extraction efficiency. Also, the reduced mixture den-
sity increased cavitation, the phenomenon that is characteristic of ul-
trasound treatment efficiency (Coussios, Farny, Ter Haar, & Roy, 2007).
4. The effects of UAE on some biological activities of polyphenols
The biological activity of polyphenols underpins their healthful
benefits because of their antioxidant, anti-inflammatory, anticancer,
and antimicrobial properties among many others. Considering the ef-
fects of technologies on outcomes, it is important that UAE is studied
more and information made available to guide study designs and future
studies. This section discusses the effects of UAE on some biological
activities of polyphenols.
4.1. Antioxidative activity
Polyphenols are known for their ability to undergo series of re-
duction and oxidation reactions due to resonance effects localized to
phenyl rings. Polyphenols are considered more efficient antioxidants
due to their diverse chemical structures, from simple to complex (Dzah,
2014). Several studies have been done in the area of antioxidant ac-
tivity assessment of plant-based polyphenols extracted with ultrasonic
treatment (Szydłowska-Czerniak and Tułodziecka, 2015; Liu, Ma, Liu,
Yang, & Zhang, 2013; Bi et al., 2011). Many methods have been de-
veloped to test the antioxidant potential of extracts, most of which are
based on the inhibitory action of extracts on free radical activity of ROS
producing compounds such as in the ABTS, trolox equivalence anti-
oxidant capacity (TEAC), ferric reducing antioxidant property (FRAP),
2,2-diphenyl-1-picrylhydrazyl (DPPH), and oxygen radical absorbance
capacity (ORAC) assays (Dzah, 2014; Mojzer, Hrncic, Škerget, Knez, &
Bren, 2016). Such methods are used to ascertain the preservation of
antioxidant potential of extracts after UAE. The TEAC assay value of
Limonium sinuatum flower extracts obtained using UAE were higher
than maceration and Soxhlet methods (Xu et al., 2017). Other studies
also showed stronger antioxidant activity of UAE extracts from different
plant sources when compared to conventional methods. According to
Teh and Birch (2014), ultrasound extracted phenolics and flavonoids
from defatted hemp, flax and canola seed cakes had higher antioxidant
potentials, by two-folds over conventional extraction methods. These
results are consistent with UAE being preferred for polyphenol extrac-
tion from plants compared to traditional methods. A summary of stu-
dies highlighting the effects of UAE on antioxidant activity of extracts is
shown in Table 1.
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Food Bioscience 35 (2020) 100547
4.2. Anti-cancer activity
Cancer is a disease that is generally characterized by uncontrolled
cellular proliferation, with a multi-phase feature, incorporating both
direct and/or indirect roles of environmental, chemical, physical, me-
tabolic, and genetic factors among others (Zhang, Binns, & Lee, 2002).
The inductive and deteriorative stages of cancer have been studied and
consistent epidemiological evidence points to the fact that a diet en-
riched in antioxidants significantly reduces the risk of many cancers
(Glasauer & Chandel, 2014; Lamson & Brignall, 1999; Parohan et al.,
2019; Russo, Tedesco, Spagnuolo, & Russo, 2017; Yasueda, Hayato, &
Toshinori, 2016). These studies suggested the use of certain dietary
antioxidants in the effective management and prevention of cancer and
related mortality. Due to their safety (depending on the extraction and
purification technology used), low toxicity and their ubiquitous nature,
polyphenols have become target study compounds in the fight against
cancer. It has also been established through studies that, in addition to
their primary antioxidative actions, they have an extensive diversity of
biological functions mainly related to control mechanisms of carcino-
genesis (Amawi, Ashby, Samuel, Peraman, & Tiwari, 2017; Cas &
Ghidoni, 2018; Zhou et al., 2016).
Polyphenols are able to prevent cancer by reducing or blocking the
harmful effects of free radicals on cells through their scavenging
properties. Their varied chemical structures make them versatile in
neutralizing free radical activities thereby preventing or reducing oxi-
dative stress to levels that do not damage cellular DNA and regulatory
protein synthesis needed for the coordination of cellular activities
(Dzah, 2014; Mojzer et al., 2016). Experimental confirmations have
established that polyphenols also influence cancer propagation, and are
able to suppress progression and contribute to the healing of damaged
cells (González-Vallinas, González-Castejón, Rodríguez-Casado, &
Ramírez de Molina, 2013; Tabrez et al., 2013). Polyphenols can protect
normal cells, have cytotoxic effects on cancerous cells, modulate
growth factor-receptor interfaces and cell signaling cascades that reg-
ulate survival of normal cells and apoptosis of cancerous cells (Mojzer
et al., 2016; Tabrez et al., 2013).
The importance of UAE in cancer studies is mainly due to its ability
to preserve the anticarcinogenic properties of polyphenols in plant ex-
tracts, as their actions have been extensively studied in various in vitro
and in vivo systems (Cas & Ghidoni, 2018; Lee-Chang et al., 2013;
Medina-Torres, Ayora-Talavera, Espinosa-Andrews, Sánchez-Contreras,
& Pacheco, 2017; Thyagarajan & Sahu, 2018; Zhou et al., 2016). Par-
ticular effects of ultrasound treatment on the anticancer properties of
polyphenols have not been given as much attention as the effects of
whole extracts. However, earlier studies have shown that polyphenols
extracted using UAE from Thelephora ganbajun had greater anti-
proliferative activities toward human breast (MCF-7), lung (A549),
liver (HepG2) and colon (HT-29) cancer cells when compared to ma-
ceration and Soxhlet methods (Xu et al., 2016). Li et al. (2017) also
extracted polyphenols from Trapa quadrispinosa Roxb. residues using
ultrasound assisted enzyme extraction (UAEE) and results showed that
extracts had higher effective antitumor action against Hela, HepG2 and
U251 tumor cells. That is, UAE has the potential to conserve and en-
hance antitumor or anticarcinogenic activities of polyphenol extracts.
Ultrasound irradiation was also used to increase the synthesis of sele-
nium containing chrysin which increased its action against cancer de-
velopment in vitro (Fonseca et al., 2017). Refer to Table 1 for a sum-
mary of important studies highlighting the effects of UAE on anticancer
properties of polyphenol and antioxidant extracts.
4.3. Antimicrobial activity
The use of UAE of polyphenolic compounds for their antimicrobial
properties is of specific interest, owing to the earlier benefits articu-
lated. Many extraction protocols have adopted the use of UAE as a
treatment method in this regard, and more so because of the possibility

Table 1
Improvements in antioxidative, anticancer and antimicrobial activity of phenol and antioxidant extracts obtained using UAE compared to conventional methods.
Material
Antioxidant activity
Flowers of L. sinuatum
Stem of T. quadrispinosa Roxb
Mung bean (V. radiata) seed coat
Blackberry (R. fructicosus) residues
Sugar beet molasses
Sugar apple (A. squamosa L.) peel
Rapeseed
6
Flowers of J. integerrima
Anticancer activity
T. ganbajun mushroom
T. quadrispinosa
Antimicrobial activity
C. paliurus
E. glaucophyllum
L. sativum
A. citriodora Palau leaves
Note: UAE = ultrasound assisted extraction; SFE = supercritical fluid extraction; UAEE = ultrasound assisted enzymatic extraction; ASE = accelerated solvent extraction; HE = hot water extraction.
C.S. Dzah, et al.
Extract UAE condition Results References
Antioxidants Ethanol (60%); solvent:solid ratio (56.9:1 mL/g); time (9.8 min); UAE- 483 μmol TE/gdw Xu et al. (2017)
temperature (40 °C) Maceration-442 μmol TE/gdw
Soxhlet- 222 μmol TE/gdw
Phenols Cellulase concentration (1.74%); time (25.5 min); temperature UAEE- 1.54 ± 0.1 mmol TE/gdw Li et al. (2017)
(49 °C); solvent/solid ratio (30:1 mL/g) HE- 1.28 mmol TE/gdw
Antioxidants Ethanol (37.6%); solvent:solid ratio (35.1:1 mL/g); time UAE- 178 μmol TE/gdw Zhou, Xu, et al. (2017) and
(46.1 min); temperature (70 °C); power (500 W) Maceration- 159 μmol TE/gdw Zhou, Zheng, et al. (2017)
Soxhlet- 138 μmol TE/gdw
Antioxidants Amplitude (91%); time (15 min) UAE- 6319 μmol TE/100 gdw Zafra-Rojas et al. (2016)
Maceration- 2568 μmol TE/100 gdw
Phenols Acidic ethanol (60 mL, 1.5M HCl); Frequency (35 kHz); power UAE- 16.7 mg TE/g Chen, Zhao, and Yu (2015)
(450 W); ethanol concentration (50%); temperature (45 °C) Maceration- 9 mg TE/g
Antioxidants Acetone (32.7%); solvent:solid ratio (20:1 mL/g); temperature UAE- 121 μmol TE/gfw Deng, Xu, Li, and Li (2015)
(67.2 °C); time (42.5 min) Maceration- 94.7 μmol TE/gfw
Soxhlet- 89.6 μmol TE/gfw
Antioxidants Methanol (50.3%); solvent:solid ratio (26.2:1 mL/g); time UAE- 62.7 mmol TE/100 g Szydłowska-Czerniak and
(13.8 min); temperature (50 °C); frequency (30 kHz); power Soxhlet- 41.1 mmol TE/100 g Tułodziecka (2015)
(150 W)
Antioxidants Ethanol (59.6%); solvent:solid ratio (50:1 mL/g); time (7 min); UAE- 1103 μmol TE/100 g Xu et al
temperature (40 °C) Soxhlet- 588 μmol TE/100 g
Antioxidants Ethanol (57.4%); solvent:solid ratio (70.2 mL/g); time UAE- antiproliferative effect against human lung (A549), breast (MCF-7), liver Xu, Zheng, et al. (2016) and
(10.6 min); temperature (40 °C); power (500 W) (HepG2) and colon (HT-29) cancer cell lines was highest compared to maceration and Xu, Zhou, et al. (2016)
Soxhlet methods.
Phenols Cellulase concentration (1.74%); ethanol (30%); time UAEE-antitumor effect against Hela, HepG-2 and U-251 tumor cell lines suggested Li et al. (2017)
(25.5 min); temperature (49 °C); solvent:solid ratio (30:1 mL/g); that it was a better alternative to preserve antitumor activity of phenol extracts than
frequency (40 kHz); power (250 W) conventional methods.
Flavonoids Temperature (50.7 °C); pH (5.08); complex enzyme Enzymolysis- UAE showed higher antimicrobial activity against Staphylococcus aureus, Xiong et al. (2019)
concentration (3.23%); power (108 W). Salmonella typhi and Escherichia coli.
Phenols Ethanol (50%); solvent:solid ratio (50:1 mL/g); temperature UAE- growth rate of bacterial lower (0.37) than for conventional extraction (0.42) Abdelkebir et al. (2019)
(40 °C); power (400 W); time (10 min)
Phenols Ethanol (70%); solvent:solid ratio (20:1 mL/g); frequency SFE extracts showed higher antimicrobial activity for freeze-dried and air-dried Rafińska et al. (2019)
(45 kHz); time (2 × 30 min); temperature (50 °C) sprouts, followed by UAE, maceration and ASE
Essential oil Solvent:solid ratio (600:30 mL/g); power (100 W); frequency Antibacterial activities increased by UAE evident in higher growth inhibition than Hashemi et al. (2018)
(30 kHz); temperature (25 °C); time (45 min) observed in conventional hydrodistillation.
Food Bioscience 35 (2020) 100547
C.S. Dzah, et al.
of eliminating or reducing toxic organic solvent use. UAE has been
observed to improve extraction efficiency and biological activity of
extracts. It was used to extract flavonoids from Cyclocarya paliurus after
initial enzymolysis by Xiong et al. (2019), and results showed higher
antimicrobial activity against Staphylococcus aureus, Salmonella typhi
and Escherichia coli compared to conventional extraction methods.
Erodium glaucophyllum, a common Mediterranean herb, known for its
health benefits, was extracted using Soxhlet and UAE, and extracts were
analyzed for their antibacterial effects on Salmonella enterica, S. aureus,
Listeria innocua, Bifidobacterium lactis and Lactobacillus casei, and anti-
viral effects on hepatitis A virus and murine norovirus. The ethanolic
ultrasound-obtained extract of the phenolic compounds showed the
highest level of bioactivity on the tested bacteria and also showed the
highest antiviral activity (Abdelkebir et al., 2019). The antimicrobial
activities of Lepidium sativum polyphenol extracts were also investigated
for 4 different extraction techniques, including UAE, assisted solvent
extraction (ASE), maceration and supercritical fluid extraction (SFE).
Results showed that SFE extracts showed the highest antimicrobial
activity for freeze-dried and air-dried sprouts, followed by UAE, ma-
ceration and ASE (Rafińska et al., 2019). Hashemi et al. (2018) also
used ultrasound to extract essential oils from Aloysia citriodora Palau
leaves and observed that the treatment increased antibacterial and
antioxidant activities of the extracts. The results were linked to the
release of more metal ions as an effect of the use of ultrasound. Table 1
shows a summary of results regarding the use of UAE and its im-
provement on the antimicrobial activity of extracts.
5. Conclusion
The use of UAE has been emphasized. The major reason why it is a
preferred extraction method used to extract active plant compounds is
its versatility and the ability to use less or no organic solvent, its nature
as a physical extraction method, its simplicity of operation, its extrac-
tion efficiency, its ability to preserve biological activity of extracted
compounds, less time dependency, and its ability to be implemented at
the industrial level, among others. The application of UAE in the food,
pharmaceutical, and cosmetic industries were highlighted and ex-
amples of successful applications in recent times have also been cited.
The use of UAE and the effects on the bioactivity of polyphenols re-
garding their antioxidant and anticarcinogenic activities and under-
lying mechanisms were also discussed.
Generally, UAE results depended largely on type of plant material,
extraction solvent and the micro-environmental extraction parameters
discussed. This means, for every plant material and ultrasound equip-
ment used, there is the need to optimize the extraction protocol to
ensure that the best results are realized in terms of extraction yields and
preservation of biological activities.
6. Recommendation for further studies
Further study is needed to understand the effect of UAE on the
composition of extracts and elucidating structural and functional
changes before and after extraction procedures by comparing with
controls. This is to help ascertain effects on degradation of compounds
and the levels of specific compounds in extracts. Also, there is the need
to study the degradative effects of UAE on bioactive molecules and their
intermediary products and their biological effects in vitro and in vivo to
ascertain the safety of the process for foods and other uses. Further
study is also needed to find out how UAE may influence the breakdown
of xenobiotics in biological materials or how it may influence the for-
mation of new compounds through hydrolytic reactions or poly-
merization, and the potency of such compounds in biological systems.
7
Food Bioscience 35 (2020) 100547
Declaration of competing interest
The authors confirm that they have no conflicts of interest with
respect to the work described in this manuscript.
Acknowledgement
This study was supported by the National Key R & D Program, China
(2016YFD0400303), the Key Research and Development Plan of
Jiangsu Province (BE2016350) and the Modern Agriculture Project of
Yangzhou (YZ2016043).
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.fbio.2020.100547.
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