Sonication, a Potential Technique for Extraction of Phytoconstituents: A Systematic Review

: Traditional extraction techniques have lost their optimum performance because of rising consumer demand and novel technologies. In this regard, several techniques were developed by humans for the extraction of plant materials from various indigenous sources, which are no longer in use. Many of the techniques are not efﬁcient enough to extract maximum plant material. By this time, evolution in extraction has led to development of various techniques including microﬁltration, pulsed electric ﬁelds, high pressure, microwave assistance, enzyme assistance, supercritical ﬂuid, subcritical ﬂuid and ultrasonication. These innovations in food processing/extraction are known as “Green Food Processing”. These technologies were basically developed by focusing on three universal parameters: simplicity, energy efﬁciency and economy. These green technologies are practical in a number of different food sectors, mostly for preservation, inhibition of microorganisms, inactivation of enzymes and extraction of plant material. Like the others, ultrasonication could also be used for the said purposes. The primary objective of this review is to conﬁne the potential use of ultrasonication for extraction of oils, pectin and phytochemicals by reviewing the literature systematically.


Introduction
Innovation and technological study, along with diffusion of technologies, are the main drivers in the face of potential challenges. Moreover, they are important elements for a model of sustainable development that can assess economic growth suitable for meeting the needs of international systems in terms of well-being in the short, medium and long term, responding to the needs of the present without sacrificing future generations' aspirations.
Changes in consumer expectations and the need to produce healthy, high-quality foods drive the evolution in the food processing industry. Emerging technologies seem to be the perfect solution to the above-mentioned characteristics. Such systems, including

Systematic Literature Review Methodology
The current review focused on reviewing reliability and efficiency of sonication for extraction of phytoconstituents from plant sources systematically [15].

Search Terms Used
"Sonication", "ultrasound", "ultrasonication", "extraction", "ultrasound-assisted extraction (UAE)" were the major search terms used for gathering the literature. Initially, 210 articles were selected from Web of Science, 172 articles were selected from Scopus and 131 articles were selected from Google Scholar.

Inclusion and Exclusion
The systematic literature review methodology has been illustrated in Figure 1.

Systematic Literature Review Methodology
The current review focused on reviewing reliability and efficiency of sonication for extraction of phytoconstituents from plant sources systematically [15].

Search Terms Used
"Sonication", "ultrasound", "ultrasonication", "extraction", "ultrasound-assisted extraction (UAE)" were the major search terms used for gathering the literature. Initially, 210 articles were selected from Web of Science, 172 articles were selected from Scopus and 131 articles were selected from Google Scholar.

Inclusion and Exclusion
The systematic literature review methodology has been illustrated in Figure 1.  It was made sure that all the articles to be included in this review should be indexed by Scopus/WOS, to be published from 2015 to 2021, to be in the English language, to be It was made sure that all the articles to be included in this review should be indexed by Scopus/WOS, to be published from 2015 to 2021, to be in the English language, to be research articles, to be peer-reviewed and should not be reports. This resulted in a selection of 340 articles. All the articles were imported to the Mendeley library and duplicates were removed, which resulted in 211 articles. Then, a deep screening was done by title, abstract and full text, which resulted in 172, 113 and finally 56 articles, respectively. The screening was done to confine studies conducted on ultrasonic extraction only, while studies on ultrasonic processing and preservations were excluded. All the articles were separated with their respective nature of bioactive compounds (22), oils (16), pectin (18), proteins (9) and combined with other technologies (6).

History and Applications of Ultrasound in the Food Industry
The history of technological advancements and the invention of ultrasound had its origins in sound experiments, with Sir Isaac Newton introducing his theory of sound waves in 1687 [16]. Ultrasound is a state-of-the-art non-thermal food processing technology that, thanks to its comparatively high efficacy, lower costs of production and environmentally friendly nature, has drawn increased interest as a replacement for or adjuvant to conventional processing techniques [17]. In the food industry, ultrasound was used for the tenderization, curing and microbial inactivation of meats [18,19]. Moreover, it enhanced bioactive elements, β-glucan content, cereal, fruit and vegetable phenolics and cereal starch extraction [6,[20][21][22][23][24]. High-intensity ultrasound extraction methods increase quality and speed of a vast range of food components such as oils, flavourings, pigments and bioactive substances, including antioxidants and essential oils from aromatic plant material, such as basil, artemisia and lavender [25].

Types of Ultrasound Equipment
The core parts of ultrasonic equipment consist of sound emitter devices, an electrical power generator and a transducer. The core part that determines the type of ultrasound is the emitter, whose primary purpose is to send the ultrasonic waves to the system physically [3]. Based on this, the ultrasonic devices that are used in UAE can be roughly divided into 2 categories, which includes ultrasonic bath mode and sonotrode (ultrasonic probe) mode.

Ultrasound Bath
In the ultrasound bath type, multiple transducers are normally mounted below a stainless-steel tank, which is the ultrasound source. Few tanks still have thermostatically operated heaters. Ultrasound levels produced by most commercial ultrasonic baths are usually adequate for washing, degassing solvents and removing adsorbed metals and organic contaminants from environmental samples, although they are less efficient for extracting matrix-bound analytes [3]. The strength should be high enough to induce cavitation within the bath extraction vessel; this is not often done with traditional ultrasonic baths [26]. A significant factor determining extraction performance is the location of the vessel within the bath. The extraction vessel must be placed just above the transducer for a bath with a single transducer at the base, as power distribution would be optimum at this location [27]. Figure 2 deeply illustrates the base parts of an ultrasonic bath. All of the parts are holed in a stainless-steel tank. There exists a bath space where the regent bottles/sample is placed. Usually, distilled water is used as a medium where the sample is placed. Usually on one side, there is a valve through which the water is removed from the system. There is a control panel on the front side through which temperature, time and frequency of the system could be controlled. There could be up to two transducers that cannot be physically seen but are located in the bottom middle of the ultrasound bath.

Ultrasound Probe Type
Probe-type sonicators can provide up to 100-fold greater power to the extraction medium than an ultrasonic bath, so an improved performance is expected. One key feature for efficient implementation of ultrasonic samples for many chemical processes is that the ultrasonic energy is not passed to the extraction vessel via the liquid medium, but is inserted directly into the device [28]. Figure 3 deeply illustrates the base parts of an ultrasonic probe type. It usually consists of a single transducer attached to a control panel with the aid of a wire, through which temperature, time and frequency of the system can be controlled. Then, there is a separate stainless-steel tank where the sample is placed and the ultrasonic treatment is given.

Mechanism of Extraction
Extraction is one of the most important unit operations in industries such as pharmaceuticals and nutraceuticals. The basic objective of extraction in these industries is to get a whole plant extract or a highly specific compound. Alongside these industries, extraction is done in the food industries in the development of natural functional foods [29].

Ultrasound Probe Type
Probe-type sonicators can provide up to 100-fold greater power to the extraction medium than an ultrasonic bath, so an improved performance is expected. One key feature for efficient implementation of ultrasonic samples for many chemical processes is that the ultrasonic energy is not passed to the extraction vessel via the liquid medium, but is inserted directly into the device [28]. Figure 3 deeply illustrates the base parts of an ultrasonic probe type. It usually consists of a single transducer attached to a control panel with the aid of a wire, through which temperature, time and frequency of the system can be controlled. Then, there is a separate stainless-steel tank where the sample is placed and the ultrasonic treatment is given.

Ultrasound Probe Type
Probe-type sonicators can provide up to 100-fold greater power to the extraction medium than an ultrasonic bath, so an improved performance is expected. One key feature for efficient implementation of ultrasonic samples for many chemical processes is that the ultrasonic energy is not passed to the extraction vessel via the liquid medium, but is inserted directly into the device [28]. Figure 3 deeply illustrates the base parts of an ultrasonic probe type. It usually consists of a single transducer attached to a control panel with the aid of a wire, through which temperature, time and frequency of the system can be controlled. Then, there is a separate stainless-steel tank where the sample is placed and the ultrasonic treatment is given.

Mechanism of Extraction
Extraction is one of the most important unit operations in industries such as pharmaceuticals and nutraceuticals. The basic objective of extraction in these industries is to get a whole plant extract or a highly specific compound. Alongside these industries, extraction is done in the food industries in the development of natural functional foods [29].

Mechanism of Extraction
Extraction is one of the most important unit operations in industries such as pharmaceuticals and nutraceuticals. The basic objective of extraction in these industries is to get a whole plant extract or a highly specific compound. Alongside these industries, extraction is done in the food industries in the development of natural functional foods [29].
The use of transducers, which are the main components of ultrasonic equipment since they are responsible for transforming mechanical or electrical energy into acoustic wave shapes, were used in the UAE. The sound wave moves across the vessel filled with the medium during the UAE until acoustic resonance is produced by transducers, and compression and rarefaction (high and low pressure regions) are formed [17]. The cavitation and implosion triggered by sonication leads to cell-wall rupture and increases the number of disrupted cells. When the cell is disrupted, the solvent enters the cell and the intracellular plant material is incorporated in the solvent [4]. Figure 4 illustrates the possible extraction mechanism of ultrasonic-assisted extraction.
The use of transducers, which are the main components of ultrasonic equipment since they are responsible for transforming mechanical or electrical energy into acoustic wave shapes, were used in the UAE. The sound wave moves across the vessel filled with the medium during the UAE until acoustic resonance is produced by transducers, and compression and rarefaction (high and low pressure regions) are formed [17]. The cavitation and implosion triggered by sonication leads to cell-wall rupture and increases the number of disrupted cells. When the cell is disrupted, the solvent enters the cell and the intracellular plant material is incorporated in the solvent [4]. Figure 4 illustrates the possible extraction mechanism of ultrasonic-assisted extraction.

Influence of Treatment Conditions on Extraction
Temperature, ultrasound frequency, extraction time and solvent/medium nature affect not only the extraction yield, but also the composition of the extract.

Influence of Temperature
Extraction temperature is a crucial factor in traditional extraction and one that promotes diffusion and permeation of the solvent into the solid matrix [17]. A higher temperature may lead to a better extraction, but it may damage the plant material [30]. The cavitation nuclei number depends on temperature. A rise in temperature from 10 to 50 °C induces an increase in tension and an increase in vapor pressure inside the cavity, which can result in a lower Pmax and in a decrease of sonochemical effects [28].
Adjusting the temperature, two things must be kept in mind: the boiling point of the solvent being used and the target component. If the temperature is above the boiling point of the solvent, there are chances of an un-economical extraction. Moreover, there are a number of different phytoconstituents that are susceptible to a higher temperate, since when the critical limit is exceeded, the component may start degrading.

Influence of Frequency
When using a high frequency, loops are shortened. Thus, inadequate time to produce adequate negative pressure prevents bubble formation [31]. Thus, cavitation bubble formation reduces as ultrasonic frequency increases. This is due to inadequate time for the rarefaction period to enable the bubble to expand and create the liquid disruption [28].
While adjusting the temperature, it must be kept in mind to determine the optimal frequency level. Using a higher frequency may lead to an uneconomical extraction process. Furthermore, a greater frequency may lead to degradation of the phytoconstituents. In a study conducted by Zhu et al. [32], a relationship between ultrasonication frequency

Influence of Treatment Conditions on Extraction
Temperature, ultrasound frequency, extraction time and solvent/medium nature affect not only the extraction yield, but also the composition of the extract.

Influence of Temperature
Extraction temperature is a crucial factor in traditional extraction and one that promotes diffusion and permeation of the solvent into the solid matrix [17]. A higher temperature may lead to a better extraction, but it may damage the plant material [30]. The cavitation nuclei number depends on temperature. A rise in temperature from 10 to 50 • C induces an increase in tension and an increase in vapor pressure inside the cavity, which can result in a lower Pmax and in a decrease of sonochemical effects [28].
Adjusting the temperature, two things must be kept in mind: the boiling point of the solvent being used and the target component. If the temperature is above the boiling point of the solvent, there are chances of an un-economical extraction. Moreover, there are a number of different phytoconstituents that are susceptible to a higher temperate, since when the critical limit is exceeded, the component may start degrading.

Influence of Frequency
When using a high frequency, loops are shortened. Thus, inadequate time to produce adequate negative pressure prevents bubble formation [31]. Thus, cavitation bubble formation reduces as ultrasonic frequency increases. This is due to inadequate time for the rarefaction period to enable the bubble to expand and create the liquid disruption [28].
While adjusting the temperature, it must be kept in mind to determine the optimal frequency level. Using a higher frequency may lead to an uneconomical extraction process. Furthermore, a greater frequency may lead to degradation of the phytoconstituents. In a study conducted by Zhu et al. [32], a relationship between ultrasonication frequency and degradation of catechin was established. It was articulated by the authors that a higher frequency might lead to the degradation of catechin.

Influence of Time
There is a great influence of time on extraction [33]. Better extraction is done with an elevated time period, but after certain limits the plant material may start degrading [34].
While adjusting the temperature, it must be noted that a longer period of time may lead to an uneconomical extraction. Moreover, a longer period of time may lead to the degradation of phytoconstituents.

Extraction of Bioactive Compounds
Effective biological active compounds are available in plants that are known as phytochemicals. Effective phytochemicals can be extracted from different parts of the plants such as barks, leaves, seed coat, seed, roots, pulps and flowers, and particularly nominated as the direct medicinal agent's sources. Phytochemistry explains that there are more secondary metabolites available in the plants [35][36][37][38][39]. Various techniques are applied to extract bioactive compounds such as flavonoids, phenolic acids, keratin, tanshinone, terpenoids, tocols, xanthones, carrageenans, a-mangostin, isoflavones, apigenin, genistin and many others [40][41][42][43].
Natural sources might be used to extract bioactive compounds, since they possess beneficial impacts on the health of human. Fruits and vegetables contain high amounts of phenolic compounds, carotenoids and vitamin C as compared to others. The process of extraction of these compounds is based on various factors such as the raw material, the organic solvent and the applied technique. Generally, conventional techniques need large quantities of organic solvents, maximum expenditure for energy and consume more time, which has produced interest in novel technologies known as green or clean technologies [44,45]. These can eliminate or reduce the toxic solvents used, and therefore preserve resources of natural environment [46].
Numerous innovative non-thermal extractions (e.g., high-pressure, pulsed electric fields, ultrasound-assisted extraction, etc.) have been suggested for the extraction of biologically active compounds. Conceptually, such techniques are "green", shorter, elude toxic chemicals and are capable to enhance the extraction quality and yields with decreased solvents and energy consumption [47]. Ultrasound could be used as green, valuable and alternative techniques to improve the bioactive compounds extraction through solvent [48]. UAE is a rapid, novel, green and developing technology appropriate for improving and scaling up the efficiency of bioactive compound extraction. Ultrasound mostly generates cavitation bubbles and acts in the biological matrix. Inclusively, it has been described for attaining high rates of extraction and yields of bioactive compounds. Furthermore, remarkable environmental benefits and economic could be improved and ultrasound has maximum potential for application and development [49]. Table 2 shows various studies conducted on the extraction of bioactive compounds by ultrasonic-assisted extraction.

Extraction of Oils
Edible plant oil (EPO) is an essential resource of nutrition for human health. Numerous oil-bearing plant cultivars are produced worldwide, and the compositions of chemicals from different oils of plants are varied. The exceptionally complex oil components lead to varied standards for estimating the safety and quality of several EPOs. The environmental stances are great encounters for the quality and safety of EPOs during the entire chain of industry, containing harvesting, plant cultivation, storage and oil processing [70].
Great importance has been given to consider the impact of ultrasound technology on the efficiency of oil extraction from seeds and on the extracted oil properties as well. The phenomenon of cavitation is persuaded by ultrasound, which improves the yield of oil as it smashes the primary seeds' cell wall and develops an easy oil release. Therefore, the maximum yield of oil is gained when UAE is utilized in comparison with conventional techniques. The UAE oil properties such as the content of free fatty acid, oxidative stability and crystallization are influenced by the ultrasonic temperature, time, solvent type and intensity during extraction [71].
Oil extraction through the UAE is likely to lessen the ecological and economic influences of the process on the oil and fat industry [72]. Extraction of oil through UAE has improved the performance and decreased the time for extraction without disturbing the quality of oil [73]. This extraction is extensively used to extract valuable intracellular components from different parts of the plant. As an escalating technique for the process, edible oil extraction through ultrasonic methods, such as avocado oil, extra virgin olive oil, flaxseed oil, sunflower seed oil, as compared to others, has improved the extracted oil (fatty acids) yield, reduced the time of extraction and avoided the consumption of solvent. Being a non-thermal technique of extraction, the operational principle of extraction through ultrasonically assisted means depends on the acoustic cavitation phenomenon. Acoustic cavitation by ultrasonic methods generates powerful shear forces, which disturb the cell walls and enhance the transfer of mass between the surrounding solvent and the interior of the cell. Therefore, ultrasonic extraction is regarded as a superior technique for the isolation and extraction of compounds entrapped in the cells of the plant [74]. Table 3 shows various studies on the ultrasonic-assisted extraction of oils.

Extraction of Pectin
Heteropolysaccharides that are mainly composed of α-1-4 d-galacturonic acid unit are known as pectin. This natural cell wall of the plant may or may not be methyl esterified and contains neutral branching of sugars that harbor moieties functionally. Physicochemical factors such as temperature, cosolute presence, pH and concentration of ions directly affect the gelling capacity and yield of pectin through extraction. The structural and chemical features of polysaccharide allow its interaction with an extensive molecule range, a property that experts utilize to form novel composite matrices for controlled/target therapeutic cells, molecules or gene delivery. As part of a measured prebiotic diet of fiber, pectin encounters various regulations, including applications of health within the pharmaceutical industry as an agent and as a raw material for cancer prevention [90]. Pectin is an appreciated hydrocolloid with numerous functional properties and applied in the cosmetic, pharmaceutical and food industries [91].
The degradation of ultrasonic methods has been converted into a promising strategy for developing modified pectin (MP). The treatment of ultrasonic methods at numerous pH values can be established as viable resources to extract the desirable MP [92]. Innovative processing techniques processing (enzymatic extraction, ultrasound-assisted extraction and microwave extraction) are utilized to extract pectin from by-products and different wastes. The extraction of pectin differs based on the studied matrix and time, pH, solvents, solid-to-liquid ratio and temperature as well. The utilization of innovative processes of extraction such as microwave, enzymes and ultrasound can be a valuable means to escalate the pectin quality and yield, and for decreasing the extraction temperature, use of toxic solvents, time and strong conditions of acids for the recovery of pectin. Furthermore, the solvent modelling combination and the particular processes of extraction can facilitate the selective pectin recovery [93]. For pectin, which is a soluble fiber, the disruption and cavitation of cells initiated by waves of ultrasounds may progress the mass transfer, and consequently enhance the process of extraction [94]. Table 4 shows various studies on ultrasonic-assisted extraction of pectin.

Extraction of Protein
Proteins perform a significant role in nourishing life through foods obtained from animals and plants. Protein contents vary in every food, and the properties of proteins are higher in foods to be performed. Proteins contribute to providing the nutritional properties in foods through the provision of amino acids that are considered to be essential in the maintenance and growth of humans; proteins provide the structural basis for several foods' functional properties [113]. Proteins are a biomolecules' ubiquitous class that perform a chief role in the food industry as constituents to impart sensory, functional and nutritional properties to the formulations of food. The proteins' ability to perform actions in these capacities depends on their exceptional physicochemical properties that are based on the protein's structure at several organizational levels in turn (i.e., quaternary, tertiary, secondary and primary) [114].
Extraction is a major stage for the recovery and isolation of proteins. Various methods such as conventional alkaline, reverse micelle, salt, enzyme extraction and organic solvent have been utilized to extract proteins from plants [18]. A unique extraction technique is required to perform the procedure of protein extraction. UAE is a proficient technique for extraction due to its extraordinary benefits of high extraction yield, low solvent quantity and short extraction time [115]. Ultrasound technique has been used extensively for peptide and protein extraction from natural products, achieving maximum yields and extraction rates. Peptide encapsulation with biodegradable polymers can improve bioavailability and stability through ultrasound-assisted methods. Furthermore, in applications of sonophoresis, minimum-frequency ultrasound can be utilized to transfer peptide drugs with maximum molecular weight [116].
UAE decreased the particle size and the microstructure dimension in gluten and albumin, representing that ultrasound can unfold aggregates of protein. Moreover, UAE enhanced the emulsifying activity (EA), solubility, foam stability (FS) and foaming capacity (FC) of the proteins. The consequences reveal that ultrasound extraction is an encouraging approach to enhance the properties and extraction yield of proteins [117]. Table 5 shows various studies on the ultrasonic-assisted extraction of protein.

Conclusions, Challenges, and Future Perspectives
The advantages of UAE are recognizable, and so the food industry is especially interested in its acceptance. Consequently, there are numerous novel techniques for enhancing this method to improve the efficiency of extraction and meet the requirements of "natural chemistry". In the current situation, ultrasound combinations with other traditional or new innovations are a unique topic. These combinations predominantly involve supercritical fluids, enzymes and microwave-assisted extractions mutual with ultrasound to achieve the synergistic impact of such techniques. To meet demands for green extraction, UAE should alter the conventional extraction solvents with unique solvents such as deep eutectic solvents, ionic liquids, cloud point techniques and multi-phase solvents. New developments in advancing ultrasonic instruments to enhance the interaction with ultrasound, having a sample matrix in a system of continuous flow, are also in request.
In the food sector, ultrasound is considered a new technology. It has the advantages of reducing taste loss, increasing homogeneity, conserving energy, increasing production, improving quality, reducing chemical and physical dangers and being environmentally friendly. Its efficiency rises when pressure and/or temperature are applied, but caution is required to determine and control nutrition.
Comparatively, despite the minimum cost of ultrasonic devices, industrial pilot-scale or even scale-up usage is deliberated due to the requirement for ad hoc modified plants, limiting the optimization and investigation of operations on a large scale. The impact of highly powerful intensities or prolonged time duration on the component's stability in the matrices of food under treatment by ultrasound could cause significant compound oxidation or degradation, which could reduce its applications and use.
The research gap should be filled with material, the location of the vessel, study length and geometric characteristics concerning ultrasound extraction. Adopting improved cavitometers may offer essential distribution information and cavitation intensity. Calorimetric tests are performed to measure the actual ultrasonic power incoming towards the vessel. In order to accomplish excellence in the industrial tests of scaling-up, geometric design, location ultrasonic power and ultrasonic strength must be taken into interpretation. UAE is not a linear procedure, so that, simply, only the ultrasonic equipment size is impractical and limited to consider, as confirmed by findings from experiments in a laboratory. Hence, other technical parameters must be taken into consideration during up-scaling, containing ultrasound strength, geometric design, kinetic studies and control. Moreover, some sturdy agents of reducing, such as ascorbic acid and ethanol, should be added to free radical scavenging generated by cavitation, therefore protecting components of food. Chemical processes and reactions under the impact of sonochemical methods on components of food are needed to be deliberated to improve and adjust the process conditions of ultrasound methods and achieve excellence in the product quality.