Green Extraction Methods for Polyphenols from Plant Matrices and Their Byproducts: A Review Kashif Ameer, Hafiz Muhammad Shahbaz, and Joong-Ho Kwon

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1 Green Extraction Methods for Polyphenols from Plant Matrices and Their Byproducts: A Review Kashif Ameer, Hafiz Muhammad Shahbaz, and Joong-Ho Kwon Abstract: Polyphenols as phytochemicals have gained significant importance owing to several associated health benefits with regard to lifestyle diseases and oxidative stress. To date, the development of a single standard method for efficient and rapid extraction of polyphenols from plant matrices has remained a challenge due to the inherent limitations of various conventional extraction methods. The exploitation of polyphenols as bioactive compounds at various commercial levels has motivated scientists to explore more eco-friendly, efficient, and cost-effective extraction techniques, based on a green extraction approach. The current review aims to provide updated technical information about extraction mechanisms, their advantages and disadvantages, and factors affecting efficiencies, and also presents a comparative overview of applications of the following modern green extraction techniques supercritical fluid extraction, ultrasound-assisted extraction, microwave-assisted extraction, pressurized liquid extraction, and pressurized hot water extraction as alternatives to conventional extraction methods for polyphenol extraction. These techniques are proving to be promising for the extraction of thermolabile phenolic compounds due to their advantages over conventional, time-consuming, and laborious extraction techniques, such as reduced solvent use and time and energy consumption and higher recovery rates with lower operational costs. The growing interest in plant-derived polyphenols prompts continual search for green and economically feasible modern extraction techniques. Modern green extraction techniques represent promising approaches by virtue of overcoming current limitations to the exploitation of polyphenols as bioactive compounds to explore their wide-reaching applications on an industrial scale and in emerging global markets. Future research is needed in order to remove the technical barriers to scale-up the processes for industrial needs by increasing our understanding and improving the design of modern extraction operations. Keywords: microwave-assisted extraction (MAE), polyphenols, pressurized liquid extraction (PLE), pressurized hot water extraction (PHWE), supercritical fluid extraction (SFE), ultrasound-assisted extraction (UAE) Introduction Plant phenolic compounds have considerable significance as bioactive compounds with substantial health benefits. There are several key factors responsible for the shifting trend toward herbal products among the consumer markets of polyphenols globally. Prominent factors include the rising proportion of aged people in the populations of Japan and Europe, increased health awareness of consumers, and the onset of various metabolic disorders due to aging (Cherniack 2011; Visioli and others 2011). A recent study conducted by Transparency Market Research, a global market intelligence group, has predicted a boom in the polyphenol market owing to increasing demands and market size. This study indicates that the global demand for polyphenols in 2018 will be expected to reach USD million. The estimated demand is based on revenue (USD million) and volumes (tons) CRF Submitted 9/20/2016, Accepted 12/6/2016. Authors Ameer and Kwon are with School of Food Science & Biotechnology, Kyungpook Natl. Univ., Daegu 41566, South Korea. Author Shahbaz is with the Dept. of Biotechnology, Yonsei Univ., 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea. Direct inquiries to author Joong-Ho Kwon ( jhkwon@knu.ac.kr, knujhkwon@hanmail.net). for the period 2012 to 2018, with an annual growth rate of 6.1% (Transparency Market Research 2016). Implementation strategy for green extraction techniques The implementation process of green extraction on an industrial scale consists of 3 tiers related to the optimization of process variables: raw materials, energy, and solvent consumption. The 3-tier implementation process is comprised of the following levelbased innovation and modification of existing protocols and technologies: (i) bringing about improvement by innovative designing and ensuring compliance with optimization strategies (Chemat and others 2012; Buckley and others 2013), (ii) exploitation of inherently undedicated equipment, and (iii) exploration of new alternatives to conventional solvents during the design of innovative processes (Cravotto and others 2011; Mustafa and Turner 2011). The current review aims to provide updated technical information about extraction mechanisms, their advantages and disadvantages, and also presents a comparative overview of the applications of modern green extraction techniques supercritical fluid extraction (SFE), ultrasound-assisted extraction (UAE), microwaveassisted extraction (MAE), pressurized liquid extraction (PLE), and C 2017 Institute of Food Technologists doi: / Vol.16,2017 ComprehensiveReviewsinFoodScienceandFoodSafety 295

2 pressurized hot water extraction (PHWE) as alternatives to conventional extraction methods (for example, Soxhlet, percolation, and maceration). Extraction techniques for plant-derived polyphenols Plant materials have been increasingly exploited to isolate and purify bioactive compounds, and recent studies have reported on the antioxidant potential of byproducts of fruits (Shahbaz and others 2016a, 2016b). Traditional techniques involve application of solid liquid extraction (SLE) simply by means of solvent application and leaching. A domestic application of conventional solvent extraction (CSE) is quite familiar to everybody in daily life from the making of coffee or tea at home. SLE encompasses conventional methods: Soxhlet extraction (SE), percolation, and maceration extraction (ME). These techniques have been utilized for more than a century for the isolation of polyphenols. However, certain disadvantages pertaining to CSE render its application quite uneconomical due to excessive consumption of time, energy, and polluting solvents (Cravotto and others 2011). These underlying drawbacks have triggered research that explores more cost-effective and greener techniques for the extraction of polyphenols from a wide range of plant matrices and their byproducts (Azmir and others 2013), as illustrated in detail in Figure 1. SFE In a broad sense, SFE has established itself as a prominent green method, particularly in the case of solid matrices, owing to the advantages described in Table 1. SFE has been widely used for value-addition to plant byproducts generated during processing. Such products apparently have no commercial significance, and extraction allows effective exploitation of waste components in order to extract the targeted phenolic compounds (Herrero and others 2010). Extraction principle and mechanism of SFE Supercritical (SC) fluid can be defined as fluid existing in a phase which possesses features of both liquids and gases above its characteristic critical temperature and pressure. Critical pressure (P c ) is regarded as the minimum quantity of pressure required to liquefy a gas at its unique critical temperature. The critical temperature (T c ) of a gas is the temperature at which the gas does not become liquid until application of extra pressure. SC fluids have become solvents of choice due to the combined properties of 2 individual phases: gaseous and liquid simultaneously. This results in an improved mass transfer rate of solutes during extraction. Hence, SC fluid provides unique properties of viscosity, density, and solvation at a phase between liquids and gases. These properties can be modified by varying temperature/pressure (Lang and Wai 2001; Pereira and Meireles 2009). The SFE system is depicted in detail in Figure 2. During the extraction process, plant raw material is fed into an extraction vessel. The desired extraction conditions are maintained by the operation of a pressure release valve and temperature controllers attached to the extraction vessel. European Food Safety Authority and the United States Food and Drug Administration have assigned CO 2 a generally recognized as safe (GRAS) status. CO 2 is the most widely used SC solvent because of its particular features, notably its economic inexpensiveness and GRAS status (Pereira and Meireles 2009; Herrero and others 2010; Khosravi-Darani 2010). CO 2 is pumped as a fluid at critical conditions (T c < K and P c = 5.7 MPa) to the extraction vessel. Heat exchangers are used to cool the CO 2 located in the inlet and outlet of the CO 2 pump (Figure 2). In the CO 2 -extract separator, the solvation power of the SC fluid is lowered by combined manipulation of temperature/pressure. The phenolic compounds dissolved in the fluid are separated from the fluid in the CO 2 -extract separator by means of an outlet valve located on the lower side of the separator. The cyclic process of SFE continues until maximum recovery rates of polyphenols are achieved from the targeted plant sample matrices (Wang and Weller 2006). Factors Influencing SFE Efficiency Correct SC fluid selection This is one of the crucial factors governing SFE efficiency for polyphenol extraction. Due to the thermolabile nature of phenolic compounds, SC water is not a good choice in spite of high extraction yields in the case of polar compounds. Polyphenols possess a low degree of solubility in SC-CO 2, making CO 2 usage alone unfavorable (King 2014). To overcome this limitation, modifiers have been added to SC-CO 2 in order to improve solubility and recovery rates of phenolic compounds. Acetonitrile, acetone, methanol, ethyl ether, ethanol, and water are the most commonly used effective polar modifiers (Pereira and Meireles 2009; Azmir and others 2013). Ethanol has been reported to be the better option as a modifier compared to others by virtue of its lower toxicity and enhanced extraction of polyphenols with a lower degree of selectivity. Water has very low solubility in SC-CO 2 and is normally not used as a modifier alone. In order to increase water solubility, binary mixtures of ethanol and water are used (Wang and Weller 2006; King 2014). Modifier effect Clean extracts with higher recovery rates are achieved by exploiting a temperature range just above the critical point at which the targeted phenolic compounds have solubility in a fluid. This also helps to minimize the extraction of unwanted compounds from matrices. Modifiers can also influence extraction efficiency during the SFE operation (Wang and Weller 2006). Higher extraction rates of a glycosylated flavonoid (naringin) have been reported from Citrus paradise when ethanol (15%) was used as modifier with SC-CO 2 at K (T c ) and 5.9 to 9.5 MPa (P c ), as compared to the yield obtained using SC-CO 2 alone. SFE results in a higher yield (14.4 g/kg in 45 min) in comparison with the yield rates obtained from ME (11.1 g/kg in 24 h) and heat reflux extraction (HRE) (13.5 g/kg in 3 h) (Giannuzzo and others 2003). Particle size effect Particle size is another factor that has an influential effect on SFE efficiency during phenolic compound extraction. Particle size is reported to influence mass transfer of solutes during the extraction process, thereby affecting polyphenol recovery rates (Pereira and Meireles 2009). In another study, the effect of particle size on SFE efficiency was investigated for the extraction of isoflavones from soybean meal. It was concluded that an optimum particle size in the range of 20 to 30 mesh provides a greater surface area and, consequently, results in increased mass transfer. Improved isoflavone yield was obtained because of enhanced extractant penetration in the matrix. Any deviation of particle size less than 20 mesh or greater than 30 mesh leads to a marked decline in isoflavone recovery from soybean meal (Zuo and others 2008). SFE applications for the green extraction of polyphenols Recently published studies have reported on the extensive application of SFE in the food sector, due to the distinctive merits 296 ComprehensiveReviewsinFoodScienceandFoodSafety Vol.16,2017 C 2017 Institute of Food Technologists

3 Figure 1 Conventional and modern extraction methods for plant-derived polyphenols. Figure 2 Operational schematic mechanism of supercritical fluid extraction (SFE) system. of SFE. Promising features include its potential as a sustainable and environmentally friendly technique that limits the use of toxic organic pollutants, improved selectivity for isolating targeted compounds, faster extraction rate, comparable yields, and utilization of food-grade organic modifiers (Pereira and Meireles 2009; De Melo and others 2014). Zuo and others (2008) extracted the soybean isoflavones (predominantly daidzein, genistein, and daidzin) from soybean meal, and the effects of various factors, such as modifier (aqueous methanol) concentration and operating conditions (P c, T c,andsc-co 2 flow rate), were investigated. CSE was compared with SFE in terms of isoflavone recoveries. After studying the effect of various factors, a maximum isoflavone yield of 87.3% was obtained with the following conditions: 80% aqueous modifier, 50 MPa (P c ) at K (T c ), 20 to 30 mesh as the optimum particle size range, with SC-CO 2 flow rate of 9.80 kg/h. SFE of isoflavones was reported to be more efficient, with a 10.2% increase in yield and rapid extraction time (the optimum is only 150 min), in comparison with CSE, which takes up to 4 h at K, and may lead to degradation of thermolabile soybeanmeal isoflavones (Zuo and others 2008). Cajaninstilbene acid (CSA) and pinostrobin (PI) are, respectively, a stilbene and flavonone from pigeon pea leaves and Kong and others (2009) compared the antioxidant activities of SFE extracts of these compounds with those recovered by HRE. After optimizing the SFE process by employing response surface methodology (RSM), a statistical process optimization technique, SFE resulted in enhanced recovery of CSA and PI under the following operating conditions: a P c of 30 MPa with ethanol (80%) as a modifier and a solid/liquid ratio of 10:1, a CO 2 flow rate of 12 kg/h at T c of K, and extraction time of 2 h. Higher yield rates of CSA (11.17 mg/g) and PI (2.73 mg/g) were achieved in the case of SFE extracts with relatively higher antioxidant capacities compared to the HRE yield rates (8.31 and 1.99 mg/g for CSA and PI, respectively). A higher SFE extract yield was achieved due to an increased mass transfer rate. Table 3 shows a comparative overview of SFE for polyphenols in comparison with other green methods. SFE process was optimized by RSM for effective and efficient extraction of flavonoids from kudzu (Pueraria lobata) owhi plant roots. The highest flavonoid contents were obtained at the C 2017 Institute of Food Technologists Vol.16,2017 ComprehensiveReviewsinFoodScienceandFoodSafety 297

4 Table 1 Advantages, disadvantages, precautions, and applications of 1 SFE, 2 UAE, 3 PLE, and 4 PHWE. Sr. no. Merits Demerits Precautions Applications References 1) Cutting down usage of organic solvents and potential risk of storage 2) Reduction in extraction time to allow process completion in about 20 min due to back-diffusion of analytes of interest in SFE process 3) Possesses excellent suitability for extraction of solid/liquid compounds with lower volatility 4) Requirements of operative conditions are relatively lower 5) Allows maximum degree of separation of solvent from target extract 6) Continual process with no intermittence 7) Cost-effective handling 8) Ease in recovery of employed solvent 9) Usage of cosolvents with cosolutes result in enhanced efficiency 1) Ease of use due to simplicity of technique 2) Increased extraction throughput of extracted materials and rapid extraction rate of thermolabile components at mild/low temperature ranges during processing 3) Increased extraction throughput of extracted materials and rapid extraction rate of thermolabile components at mild/low temperature ranges during processing Extended time due to low rate of diffusion of solute from solid matrix in to the SCF Imprecise modeling can affect efficiency of SFE Scalability is impossible due to lack of molecular model of solutes diffusion in to SCF Requirements for high pressures of SC fluids and costly infrastructure such as CO 2 pumps and pressure vessels Variation may be brought about in terms of consistency and reproducibility of continuous process of extraction CO 2 cannot always be used as SC solvent due to its nonpolar nature for polar solutes Postextraction residual solvents disposal issues from plant matrices complying to EPA regulations Availability of solvent is necessary in order to carry out optimum extraction of bioactive compounds Degradation of active principles from plant matrices occurs due to oxidative pyrolysis caused by hydroxyl (OH-) radicals during cavitation phenomenon Degradation of active principles from plant matrices occurs due to oxidative pyrolysis caused by hydroxyl (OH-) radicals during cavitation phenomenon SFE Provision of adequate contact time for proper solvent penetration into plant matrices for diffusion Achievement of equilibrium (phase equilibrium of solvent and solutes) UAE Careful experimentation required to choose optimum solvents for high recovery Recovery of natural products and thermosensitive polyphenols from wide range of plant matrices Phenolic compounds and flavors Ginger Eucalyptus Soybean Coffee Orange peel Byproducts recovery from fruits and vegetables Extraction and recovery of natural products Nondestructive method for extraction of active principles from vegetable matrices Nondestructive method for extraction of active principles from vegetable matrices (Herrero and others 2010; Sairam and others 2012) (Herrero and others 2010; King 2014) (Herrero and others 2010; Sairam and others 2012) (Ghude and others 2013; King 2014) (Sairam and others 2012; King 2014) (Herrero and others 2010; King 2014) (Herrero and others 2010; Sairam and others 2012) (Sairam and others 2012; King 2014) (Sairam and others 2012; King 2014) (Vilkhu and others 2008; Tadeo and others 2010) (Vilkhu and others 2008; Kentish and Feng 2014) (Vilkhu and others 2008; Kentish and Feng 2014) (Continued) 298 ComprehensiveReviewsinFoodScienceandFoodSafety Vol.16,2017 C 2017 Institute of Food Technologists

5 Table 1 Continued Sr. no. Merits Demerits Precautions Applications References 4) Less time consuming as compared to traditional techniques, such as, Soxhlet extraction, maceration and hydrosilization) 5) Low cost and economically viable choice for green extraction of polyphenols 6) Advantageous due to diminishing laboratory wastes 7) Coupling with other techniques such as, MSPD, enables enhanced extraction of plant matrices without further purification 8) Maximum compatibility of UAE with GRAS solutions 9) Ultrasounds allow penetration of solvents to greater depths in sample matrices to facilitate the increased mass transfer of solutes to extraction solvent 10) Minimum degree of interaction of ultrasonic waves with extracted materials during extraction process 1) Extraction of target analytes efficiently in faster manner from solid plant matrices 2) Increased wetting of matrix molecules by solvent and enhanced penetration 3) Reduced viscosity of employed solvent at elevated temperature and pressures, resulting in increased solubility High ultrasound waves bring about deleterious effects in active constituents in plants by free radical formation and result in undesirable changes in extracted components Dilution of extract is one of the major drawbacks in case of dynamic ultrasound-assisted extraction (DUAE) Requirement of sophisticated and specialized automated equipment Economic consideration due requirement of various columns (Silica gel) for removal of food samples in destructive manner Need for continual improvement of automation levels for reduction of sample preparation bottlenecks with analyst intervention to minimum degree PLE Care must be taken to select solvent mixtures from wide range of choices, especially modifier and surfactant assisted in terms of sustainability and safety Extraction of polyphenols from plant matrices/ byproducts or waste parts (bark, leaves, peel, and seeds) Intensification of bioactive compounds (polyphenols) from natural plant sources Polyphenols and nutraceuticals from wide range of plant matrices Bioactive compounds from herbal sources Isoflavones Flavonones Antioxidants (Vilkhu and others 2008; Kentish and Feng 2014) (Knorr and others 2011; Simsek and others 2012) (Tadeo and others 2010; Awad and others 2012) (Tadeo and others 2010; Kentish and Feng 2014) (Kentish and Feng 2014) (Vilkhu and others 2008; Awad and others 2012) (Awad and others 2012; Kentish and Feng 2014) (Mustafa and Turner 2011; Knorr and others 2011; Heng and others 2013) (Mustafa and Turner 2011; Knorr and others 2011; Heng and others 2013) (Carabias-Martínez and others 2005; Knorr and others 2011) (Continued) C 2017 Institute of Food Technologists Vol.16,2017 ComprehensiveReviewsinFoodScienceandFoodSafety 299

6 Table 1 Continued Sr. no. Merits Demerits Precautions Applications References 4) Increased mass transfer by facilitating breakdown of matrix-analyte bonds facilitating solute diffusion from plant matrix 5) Reduced time and solvent usage with advantage of online coupling with instrumental separation techniques (GC & HPLC), and automation 1) Employment of water as eco-friendly extractant with similar polarity to that of organic solvents (for example, alcohol) with minimum disposal issues 2) Facilitates diffusion of variety of solutes within range of low to medium polarities with improved selectivity Lower recovery rates of potentially thermosensitive polyphenols at elevated temperatures Incomplete extraction under static mode due to limited extractant volume Addition of different additives and purpose-based modifiers may result in alteration of physicochemical properties of superheated water Requirement of micelle-mediated PHWE with Triton X-100 for thermosensitive components PHWE Maintenance of constant pressure to ensure subcritical water conditions Extraction of numerous phenolic compounds (Flavonoids and nonflavonoids) from vast range of plant matrices Anthocyanins Hydroxycinnamic acids Flavonols Flavones Flavonols Flavanols p-coumaric acid (Carabias-Martínez and others 2005; Mustafa and Turner 2011) (Mustafa and Turner 2011; Santos and others 2012) (Teo and others 2010; Plaza and Turner 2015) (Teo and others 2010; Vergara-Salinas and others 2015; Plaza and Turner 2015) 3) Reduction of organic solvents usage to greater extent 4) Nontoxic and cost-effective extraction technique of organic components from wide array of plant matrices/ byproducts 5) Low operational and maintenance requirements as compared to other sophisticated techniques 6) Improved aid in bioremediation procedures as being green extraction method 1 SFE (Supercritical fluid extraction). 2 UAE (Ultrasound-assisted Extraction). 3 PLE (Pressurized fluid extraction). 4 PHWE (Pressurized hot water extraction). (Vergara-Salinas and others 2015) (Teo and others 2010; Plaza and Turner 2015) (Vergara-Salinas and others 2015) (Vergara-Salinas and others 2015) following set conditions: a T c of K, SC-CO 2 flow rate of 20 L/h, with approximately 181 ml ethanol modifier at a P c of 20 MPa (Wang and others 2008a). Ethanol used as cosolvent caused an increased polarity of SC-CO 2, which resulted in improved extraction yields of flavonoids from plant roots. Moreover, the model-predicted values showed a fair match with experimental values under optimum conditions. Rice wine lees was investigated for antioxidant activity of phenolic compounds from SFE extracts. Ethanol (as the employed modifier) in combination with SC-CO 2 has been described as a critical factor for enhanced SFE efficiency for polyphenols. SFE has been compared with SE in terms of extract yield and extraction times. SFE yielded 43% of total SE extract yield. In contrast, the SFE process has been reported to consume considerably less ethanol (approximately one-tenth of the amount used in SE) and time (only 1 h compared to 6 h in the case of SE). Polyphenol extraction was found to increase with a corresponding increase in 95% ethanol volume during SFE. A final yield rate of 11.9% was reported using the following extraction conditions: P c (35 MPa) and T c (313 K) with SC-CO 2 flow rate of 25 ml/min (Wu and others 2009). 300 ComprehensiveReviewsinFoodScienceandFoodSafety Vol.16,2017 C 2017 Institute of Food Technologists

7 UAE UAE has emerged as a promising technique that fulfills the required criteria as an inexpensive green extraction technique. Notable UAE features include versatility, simplicity, safety, rapidity, eco-friendliness, and cost-effectiveness, due to the reduced consumption of time, energy, and expensive organic solvents, which is in contrast to traditional extraction techniques (Wang and Weller 2006; Azmir and others 2013). The advantages, disadvantages, and limitations of UAE are presented in Table 1. Extraction principle and mechanism of UAE Acoustic waves are classified as longitudinal waves that require a certain medium for their propagation. However, ultrasound waves differ from normal sound waves by virtue of their relatively higher frequencies than those of the normal audible range of humans ( 20 Hz to 20 khz) (Priego-Capote and de Castro 2004; Azmir and others 2013). As ultrasound has longer wavelengths, typically in the millimeter (mm) range, which are longer than medium-sized molecules, chemical changes are not brought about by the direct interaction of waves with matrix molecules. Instead, chemical changes are brought about due to phenomenal changes, resulting in implosion caused by massive energy production (de Castro and Delgado-Povedano 2014; Kentish and Feng 2014). Generally, the most widely used extractor device for sonication is an ultrasonic bath, as shown in Figure 3. In order to conduct sonication for extraction purposes, the operational frequencies of ultrasound waves generally range from 20 khz or above. When media are exposed to such high frequencies, ultrasound waves produce their effects by transmittance of massive energy and pressure, which are radiated by base transducers to the targeted sample causing cavitation (Figure 3). Strong ultrasonic waves result in the formation of bubbles in liquid media upon interaction with a matrix. The bubbles continue to absorb energy up to their maximum limit, and further exposure to ultrasonic waves causes the bubbles to grow and collapse; in sonochemistry, this collapse is described as cavitation (Azmir and others 2013). As a consequence of this collapse, a considerable amount of energy is produced, which occurs in an uncontrollable manner in each direction in the ultrasonic bath tank (Figure 3). This massive energy release causes significantly extreme changes in temperature (up to 5000 K) and pressure (100 MPa) within bubbles during extraction, causing liquid solutes to leach at speeds of 280 m/s (Vilkhu and others 2008; Vázquez and others 2014). Figure 3 provides a detailed schematic overview of the UAE mechanism. Upon sonication, ultrasonic waves break up solid particles (disruption) and remove inert material layers, which may cause passivation, resulting in an increased surface area for mass transfer of solutes during extraction (Figure 3). Factors Influencing UAE Efficiency Operational conditions Application of ultrasound during extraction influences other process variables, namely, the extraction temperature and pressure. A reduction in temperature occurs due to the applied ultrasound during operation, making UAE a preferred choice for the extraction of thermosensitive phenolic compounds from a wide range of plant matrices. However, it is noted that this temperature change can be unfavorable in terms of extract recovery, due to changes in extraction time. Consequently, temperature should be regulated carefully during optimization studies (Wang and Weller 2006). Ma and others (2008) have observed a declining trend in hesperidin yield from citrus peel due to thermal degradation of phenolic compounds at elevated temperatures during longer extraction times. Sonication parameters (power, temperature, and frequency). Lower frequency has been reported to be correlated with increased cavitation during UAE. Increased efficiency is obtained due to the positive influence on mass transfer of solutes from plant matrices. The porous nature of plant matrices is also found to be affected by the applied frequency during sonication. This necessitates optimization studies for enhanced extract yields of phenolic compounds (Wang and Weller 2006). Hesperidin extract yield was found to be higher ( mg/g DW) from Satsuma mandarin peel under an optimum frequency of 60 khz instead of 100 khz, K temperature for 20 min extraction time, and 8 W power, compared to ME for 8 h, which resulted in a lower recovery rate (601.2 mg/g DW). It was also noted that decreased recovery of hesperidin was obtained with a gradual increase in extraction process variables. Therefore, the authors stressed the need for carefully optimized application of UAE (Ma and others 2008). UAE applications for the green extraction of polyphenols. UAE of isoflavones from Pueraria lobata (Wild.) ohwi stem was carried out and extraction efficiency was compared with that of CSE using aqueous solutions of n-butanol (95%) and ethanol of 2 concentrations: 95% (v/v) and 50% (v/v) (Huaneng and others 2007). The authors found UAE to be more efficient for total extract yield of isoflavones than CSE under the following extraction conditions: 50% aqueous ethanol (extractant), 650 W ultrasonic power at K with agitation at 300 rpm. A positive correlation was also observed between extract yield and ultrasonic power. Similarly, UAE was used to carry out the extraction of phenolic acids (caffeic acid, p-coumaric acid, ferulic acid, sinapic acid, protocatechuic acid, and 4-hydroxybenzoic acid) from Satsuma mandarin (Citrus unshiu Marc.) peels and compared with ME as a control. The authors investigated the effects of different operational parameters on phenolic compound extraction from peel matrix: sonication time (10 to 60 min), temperature levels (288.15, , and K) at different ultrasonic power levels (3.2, 8, 30, and 56 W). Ultrasonic power resulted in higher extract yields of phenolic acids than those obtained by conventional ME for 8 h expressed in µg/g DW units as follows: caffeic acid (UAE = 64.28, ME = 31.7), p-coumaric acid (UAE = 140, ME = 63.1), ferulic acid (UAE = 1513, ME = 763), sinapic acid (UAE = 133, ME = 132), protocatechuic acid (UAE = 15.8, ME = 20.6), and 4-hydroxybenzoic acid (UAE = 34.1, ME = 23.5). However, degradation of phenolic acids was reported to take place at high temperatures for longer periods of time under UAE. Therefore, the UAE technique must be used carefully by optimizing all parameters for extraction in order to avoid thermal degradation of phenolic compounds. Maximum yields of phenolic acids were reported using the following optimized operational parameters: 20 min of extraction time at K temperature and 8 W ultrasonic power (Ma and others 2008). The potential of UAE was exploited for a comparative study with traditional mix-stirring (TMS) regarding the efficiency of extracting isoflavones from freeze-dried soybeans. The extract yield of soy isoflavones was found to be higher in the case of UAE extracts. Optimal UAE parameters for enhanced soy isoflavone extraction at K comprise a sonication power of 200 W for 20 min at 24 khz frequency. Under these optimized conditions, sonication led to an enhanced extract yield of isoflavones (1180 µg/g DW) from soybeans compared with that obtained using the TMS method (1098 µg/g DW), which was used as a control (Rostagno and others 2003). C 2017 Institute of Food Technologists Vol.16,2017 ComprehensiveReviewsinFoodScienceandFoodSafety 301

8 Figure 3 Operational schematic principle of ultrasound-assisted extraction (UAE) system. In another instance, UAE for anthocyanin, antioxidant, and total phenolic contents from grape seed was optimized by a central composite rotatable design using RSM. Extraction time as a process variable was reported to play an influential role in enhancing the total extract yield of anthocyanins (2.29 mg/ml), total phenolic content (5.41 mg GAE/mL), and increased antioxidant activity (12.28 mg/ml). The optimal extraction conditions for anthocyanins were found to be an ethanol concentration of 53% and K temperature for 29 min extraction time, while keeping the ultrasonic power and frequency constant: 250 W and 40 khz, respectively. The authors reported a reasonable match between the predicted and real values of response variables after optimization (Ghafoor and others 2009). In conclusion, UAE has a demonstrated edge over traditional extraction techniques and has proven to be more suitable for polyphenol recovery as a modern green extraction technique. Peculiar features differentiating UAE from conventional techniques include decreased solvent consumption, easy residual recovery from plant matrix in bound form, rapid and substantial recovery rates of polyphenols, and suitability of the UAE method for routine analysis due to cost-effectiveness of equipment and infrastructure (Wang and Weller 2006; Vilkhu and others 2008). Table 3 presents a comparative overview of the UAE of polyphenol from various plant matrices in comparison with other extraction methods. MAE Initially, all technologies collectively known as microwaveassisted processes (MAPs) were developed and patented by the Canadian Department of the Environment (Environmental Technology Centre). These methods were developed for the extraction of bioactive compounds from various targeted plant matrices and their byproducts. A review of the published literature indicates that this technique is also acknowledged as a clean process technology with several environmental, economic, and social advantages (Kwon and others 2003a, 2003b). The advantages, disadvantages, and limitations of MAE are tabulated in Table 1. Principle and mechanism of MAE. MAE is an efficient and promising method involving derivation of natural compounds from raw plants or their byproducts. The MAE process allows rapid and efficient extraction of polyphenols with similar or better yields as compared to conventional techniques (Abdel-Aal and others 2014). Two oscillating perpendicular fields, electric and magnetic fields, act directly to heat materials having the ability to convert part of the absorbed energy to thermal energy. MAE offers several advantages over CSE, including reduction in extraction time, improved yield, better accuracy, and suitability for thermolabile chemical components (Delazar and others 2012; Azmir and others 2013). Dried plants contain minute microscopic traces of moisture serving as target for microwave heating. High temperature and pressure is generated inside the oven upon interaction of microwave radiation with chemically bound water molecules. High temperature causes the dehydration of cellulose leading to decreased mechanical strength. The MAE process consists of several steps in order to achieve efficient extraction of phytochemicals, particularly polyphenols from plants (Veggi and others 2013). The MAP starts with the generation of electromagnetic waves from a cavity magnetron (Figure 4). Tissues and cell walls of plants and their byproducts inside the plant matrix interact with the emitted radiation waves. This interaction results in the heating up of moisture trapped inside the plant matrix due to absorption of the characteristic photonic energy of electromagnetic waves. Electromagnetic energy causes moisture evaporation from the plant matrix. This causes considerable pressure to be exerted on plant cell walls at the cellular and subcellular levels, resulting in the swelling of plant cells during the MAE process. This swelling eventually brings about structural changes in the plant matrix, thereby promoting an increased mass transfer of solutes due to the rupturing of cells. This, in turn, facilitates phytochemical leaching from the plant cellular matrix into the extractant during MAE (Delazar and others 2012; Azmir and others 2013; Veggi and others 2013). Commercial MAE system types Commercially, 2 types of MAE systems are available for industrial and commercial applications for natural product extraction: (i) the closed-vessel system and (ii) the open-vessel system (Figure 4). A comparison regarding the advantages and disadvantages of commercial MAE systems for extraction purposes is presented in Table ComprehensiveReviewsinFoodScienceandFoodSafety Vol.16,2017 C 2017 Institute of Food Technologists

9 Figure 4 Operational schematic principle and mechanism of microwave-assisted extraction (MAE) system. (a) Open-vessel MAE system. (b) Closed-vessel MAE system. Closed-vessel system (multimode) In this system, extraction is carried out under controlled conditions of temperature and pressure. This is generally employed for extractions under extremely high temperature conditions (Wang and Weller 2006). Diffused microwaves from a cavity magnetron radiate in all directions to interact with plant samples placed in extraction vessels in a closed-vessel chamber. Owing to the even dispersion of microwaves, this technique is also known as the multimode system (Figure 4). Open-vessel system (monomode) In this system, also known as the monomode system, the extraction vessel is partially exposed to microwave radiation (focused radiation) (Mandal and others 2007). A circular metallic waveguide directs the focused microwaves toward the extraction vessel inside the microwave (monomode) cavity. This interaction promotes the initiation of mass transfer between the solute and extractant upon solvation, as shown in Figure 4. Factors Influencing MAE Efficiency The efficiency of the MAE process is subjected to changes caused by various factors: extractant nature, microwave irradiation power, extraction temperature and time, the peculiar characteristics of individual plant matrices, and the solvent-to-feed (S/F) ratio. A detailed description of the factors influencing this technique is provided in the next section. Microwave power During the process of phenolic compound extraction, high microwave power levels can result in poor recovery rates due to degradation of thermolabile components. It is noted that the extraction rates of phenolic compounds from various plant matrices have been shown to increase up to certain levels followed by a declining trend in extraction yields. Evidently, the sample matrix becomes heated because of localized interaction with microwaves. This phenomenon leads to a higher diffusion of polyphenols out of the plant matrix and into the extractant (Chan and others 2011). In the case of Oolong tea, the total phenolic content increased with a rise in extraction temperature, and the optimum extract yield was achieved at K. Reduced yields were reported beyond the optimum extraction temperature, confirming the importance of an optimal combination of microwave power and temperature for high extract yields of thermolabile phenolic compounds from targeted plant matrices (Tsubaki and others 2010). Extraction time. During MAE, the extraction time is an important influential factor, along with microwave power and temperature. As mentioned previously, exposure to microwave radiation for longer time periods decreases overall extract yield due to disruption of the structural integrity of chemically active principles (polyphenols) present in plant matrices. To circumvent thermal degradation of phenolic compounds, extraction time during the MAE process can be manipulated by controlling exposure, ranging from a few minutes to 30 min, excluding the solvent-free MAE. Moreover, in the case of longer extraction times, extraction cycles can be employed in order to reduce the degradation of phenolic compounds. This can be accomplished by repetition of the extraction procedure until completion, with subsequent addition of extractant during the extraction cycle (Chan and others 2011). Pan and others (2003) have investigated the MAE process of tea polyphenols and tea caffeine from tea leaves under various experimental conditions. They found that MAE proved to be more advantageous in terms of fast extraction with higher yield rate. For the extraction of phenolic compounds from tea leaves, MAE is completed in a shorter time interval (4 min) using ethanol compared with CSE (20 h) at room temperature and HRE (45 min). Features of the plant matrix. Apart from other factors, the characteristic nature and features of individual plant samples also influence efficiency of the MAE process. Prior to MAE, optimum extraction of phenolic compounds demanded that the desired sample should be in particular forms: finely ground powdered sample, dried, sieved, or preleached. Very small-sized sample particles will C 2017 Institute of Food Technologists Vol.16,2017 ComprehensiveReviewsinFoodScienceandFoodSafety 303

10 Table 2 Comparison of closed-vessel and open-vessel MAE systems according to intrinsic advantages and disadvantages Closed-vessel system Open-vessel system Sr. no. Merits Demerits Merits Demerits References 1) Higher temperature, constraints of closed vessel system renders reduced extraction time 2) Avoidance of loss of volatile substances 3) Less solvent requirement due to absence of evaporation phenomenon 4) No production of hazardous fumes during pressurized extraction under closed-vessel system 5) High yield by using ionic liquids (IL s) at ambient temperature (70 F/ K) 6) Simple procedural set-up without any inherent complexity as compared to SFE and other techniques Application of high pressure poses safety risks High solution temperature are not permissible by constituent material of vessel Impossibility of regent addition since it is single step process Constraint of cooling down vessel before opening rendering prevention of volatile constituents Handling and processing of limited sample volumes Requirement of cooling step after each treatment for further processing Enhanced and safer possibility of reagent addition Utilization of vessel manufactured from various materials that is, quartz or glass Easy removal of excessive quantities of employed solvents Easy processing of larger samples volumes No need of operational cooling down or depressurization Cost-effective availability of sophisticated equipment for polyphenol extraction More effective for extraction of thermosensitive phenolic compounds than closed-vessel Comparatively exhibit less precision than in close-vessel system Inability to process multiple samples simultaneously due to low throughput of equipment Longer time spans are required than closed-vessel system (Zhang and others 2011; Veggi and others 2013; Destandau and others 2013) (Mandal and others 2007; Alupului and others 2012; Afoakwah and Teye 2012) (Zhang and others 2011; Delazar and others 2012; Alupului and others 2012) (Alupului and others 2012; Afoakwah and Teye 2012) (Zhang and others 2011; Afoakwah and Teye 2012; Veggi and others 2013) (Delazar and others 2012; Veggi and others 2013; Destandau and others 2013) (Alupului and others 2012) lead to difficult separation of the extract from plant residues upon completion of the extraction process. This will necessitate an additional clean-up step after extraction of phenolic compounds from plant matrices (Ruan and Li 2007; Chan and others 2014). Furthermore, pretreatment of powdered samples with extractant for 90 min prior to the extraction step has been reported to enhance MAE efficiency. This resulted in improved kinetics, such as improved mass transfer and increased diffusion rate of phenolic compounds from plant sample residues (Kaufmann and Christen 2002). In the case of dried plant sample matrices, pretreatment with water has been reported to promote the heating effect of microwaves in a localized manner. It was noted that heating up of moisture present in the plant sample matrix continued to increase as the extraction process progressed and resulted in higher evaporation rates. By allowing the release of polyphenols from plant molecules due to matrix rupturing, this caused a further rise in the internal pressure within the extraction cell, producing higher extraction yields of phenolic compounds. A high moisture content in plant matrices favors a high hydrolyzation tendency, which improved the diffusion of solute molecules (Alfaro and others 2003; Wang and Weller 2006; Mandal and others 2007; Azmir and others 2013). Stirring effect. With the introduction of stirring during the MAE process, the negative effects of the S/F ratio upon extraction recovery can be minimized (Chan and others 2011). Furthermore, concentrated polyphenols as bound active principles in the plant matrix lead to the creation of a barrier to mass transfer rate due to a deficiency of the extractant. Stirring action helps to reduce this barrier, thereby enhancing the extraction yield by causing accelerated agitation, which leads to increased extraction efficiency (Ruan and Li 2007). Effect of additives and solvent choice. Binary solutions of organic solvents with water were reported to have a desirable impact on extraction efficiency. In this regard, it is also noted that the presence of water in organic solvents leads to enhanced penetration of the extractant in matrix molecules. This subsequently promotes microwave heating and imparts a positive impact on overall efficiency and extraction time compared with MAE using organic solvents alone (Alfaro and others 2003; Wang and Weller 2006). Solvent toxicity is another important factor that must be evaluated regarding the selection of a suitable extractant for MAE. For instance, a recent study was conducted by Makris and others (2015) to investigate the effects of solvent toxicity on the extraction of phenolic compounds from red grape pomace by utilizing 2 aqueous solutions of glycerol/tartaric acid. Upon optimization by Box-Behken using the RSM approach, they concluded that glycerol was a more suitable choice for enhanced flavonoid recovery. Tartaric acid was found to exert a negative effect with regard to phenolic compound recovery from grape pomace. In the case of phenolic compound extraction from grape seeds and skin, methanol has shown a relatively better performance as an extractant in terms of higher recovery rates in contrast to ethanol, which resulted in lower extract recovery with higher antioxidant activity (Casazza and others 2010). MAE efficiency was reported to be enhanced if the plant material is impregnated with alternative solvents, such as an ionic liquid (IL) at room temperature, in comparison with traditional organic solvents alone. The advantages associated with IL addition include higher heating 304 ComprehensiveReviewsinFoodScienceandFoodSafety Vol.16,2017 C 2017 Institute of Food Technologists

11 efficiency, viscosity, tenability, and excellent thermal stability under microwave irradiation treatment (Mandal and others 2007). MAE applications for the green extraction of polyphenols Colored grains from diverse origins (blue wheat, purple corn, and black rice) are rich sources of polyphenols and the efficiencies of different methods used for their extraction have been compared: CSE, MAE, and accelerated solvent extraction (ASE) for anthocyanins (water-soluble flavonoids). After optimization by full-factorial experimental design, higher extract recovery rates of anthocyanin from colored grains were achieved with both ASE and MAE compared to those obtained by CSE. ASE has been described as being more effective than MAE at the following optimum conditions: acidic methanol as solvent, 300 W power, and K temperature for 10 min. Anthocyanins were affected to minimal degree in terms of structural changes in the case of ASE at the following set conditions: 100% flush by 5 cycles for 10 min at K and MPa using aqueous acetone as a solvent (Abdel-Aal and others 2014). Dhobi and Hemalatha (2009) have compared MAE with conventional methods, namely, ME (24 h), SE (12 h), and MSE (24 h), for the extraction of silybinin (a flavonolignan) from the roots of Silybum marianum. Owing toincreased mass transfer, MAE has been reported to result in the highest extract yield (97.3%) as compared to those obtained from MSE (35%), ME (26.3%), and SE (79.6%). The optimum MAE conditions were reported to be 600 W of power, ethanol as solvent (80%), and an S/F ratio (25:1) at 12 min of extraction time. MAE has been exploited for the extraction of health-promoting flavonoids from artichoke herb (Cynara scolymus L.) leaves. The authors compared the efficiencies of MAE and CSE methods. The multimode MAE system was used for extraction purposes under the following operational conditions; to K temperature, 0 to 400 W power, and 0 to 2 MPa pressure. MAE efficiency was found to be better (74%) than CSE (70.5%) in terms of flavonoid recovery yield under reduced extraction temperature ( K) and time (1 to 2 min). The microwave power and pressure were described as temperature-dependent important process variables. The authors also highlighted the necessity for further research to scale-up MAE as a green and rapid extraction technique for thermosensitive phenolic compounds at an industrial scale (Alupului and others 2012). Similarly, Routray and Orsat (2014) identified high-bush blueberry (Vaccinium corymbosum) as a potent source of flavonoids, particularly chlorogenic acids and anthocyanins. They evaluated MAE, UAE, and CSE techniques in terms of extraction efficiencies for flavonoids from the leaves of the Bluetta variety of blueberry. The authors reported on the use of different levels of microwave power (10% to 20%) with extraction times spanning from 4 to 16 min with 80 ml solvent in combination with a 97:3 (v/v) ratio of 30% ethanol and 1.5 M citric acid. Microwave power and extraction time were found to be positively correlated with a higher recovery yield of flavonoids. MAE was claimed to be more efficient in terms of total phenolic content yield (92 to 128 mg GAE/g DW) compared to yields obtained by sonication for 1 h (97 mg GAE/g DW) and ordinary room temperature extraction for 24 h (89 mg GAE/g DW) using the same combination of solvents. Therefore, MAE was reported to be the most efficient among all methods, followed by UAE, as an alternative method in circumstances where no MAE apparatus is available. Table 3 presents a comparative overview of the polyphenols extracted from various plant matrices using MAE as a green extraction technique. PLE PLE is another green extraction technique for natural product extraction from food and botanical sample matrices. The Dionex Corporation was the first to introduce the PLE technique as an ASE technology (ASE R ) in 1995 (Benthin and others 1999). The advantages, disadvantages, and limitations of PLE are presented in Table 1. Extraction principle and mechanism Using PLE, a relatively faster extraction rate is attained due to a combination of the following: (1) liquid solvent interaction with matrix molecules and (2) elevated temperature and pressure for efficient extraction of targeted components. Elevating the temperatures of employed solvents above their atmospheric boiling points allows increased solubility and mass transfer rates between the plant matrix and the solvent of choice. Eventually, enhanced diffusivity of the solvent and plant matrix causes more prominent extraction kinetics. The application of elevated temperature decreases extractant viscosity, resulting in enhanced wetting of the plant matrix, and this leads to high solubility of the targeted molecules. It also causes breakage of bonding forces (dipole-dipole, van der Waals, and H 2 -bonding) in order to facilitate diffusion of targeted phenolic compounds to the outer surfaces of solid matrices. Eventually, increased diffusion rates allow high extraction efficiencies with improved recovery rates (Carabias-Martínez and others 2005; Wang and Weller 2006). Figure 5 shows the basic set-up of a pressurized liquid extractor. During the extraction process, the sample is placed into the extractor, followed by solvent pumping into the extraction vessel using an HPLC pump. The sample placed in the extraction cell is maintained at the desired temperature, using an electric heating jacket, until the required pressure is attained. After the desired combination of temperature and pressure variables is reached, the extraction process commences. Extraction processes having more than 1 extraction cycles involve extraction solvent replenishment during each extraction cycle. Owing to back pressure, blocking valves are opened carefully after completion of the extraction cycle at an appropriate level in order to maintain the desired flow rate. Once the extraction process is completed, the heating system and HPLC pump are shut down. Inert gases such as nitrogen may or may not be utilized for purging the pressurized liquid extractor for the removal of residual solvent within the extractor. Factors Influencing PLE Efficiency The factors that influence PLE extraction efficiency include matrix characteristics, choice of solvent, and extraction time and temperature. Solvent choice and toxicity. When selecting a suitable extractant, choice is always governed according to the famous notion like dissolves like. Therefore, an appropriate solvent and analyte combination is necessary to achieve higher diffusion and mass transfer rates, resulting in increased yield rates. Other factors that must be taken into account in this regard include solvent safety and toxicity, along with economic aspects (Piñeiro and others 2004; Plaza and others 2013). Non-harmful solvents with lower toxicity and ease of removal are good choices. Solvents that are termed as green should be preferred as they cause minimum environmental impact after their usage for extraction purposes. In PLE, various binary (mixture) solvents have been used for extracting phenolic compounds from various foodstuffs. Binary solvents such as methanol-water or ethanol-water have been found to be more effective and environment-friendly than pure organic C 2017 Institute of Food Technologists Vol.16,2017 ComprehensiveReviewsinFoodScienceandFoodSafety 305

12 Table 3 Comparison of green extraction techniques for polyphenols from various plant matrices/plant byproducts. Plant sample Huáng qí (Radix astragali) Green extraction technique Plant matrix/part Target phenolic compound MAE Dried root Flavonoids MP W, 90% ethanol, extraction temperature ( K), S/F ratio (1.190), 2 extraction cycles Chilean papaya UAE Seeds Isothiocyanates, phenolic acids, and flavanols Sea-buckthorn MAE Fruit, leaves, and seeds Optimum extraction parameters Extraction time Remarks Reference 5 g papaya seeds+ 250 ml of 80% aqueous methanol, 42 khz F and 130 W UP 3 of ultrasound bath extractor Flavonoids No solvent addition. 400 W MP at power density (1 W g 1 ) Citrus UAE Peel Flavonoids 60 khz F at K temperature and methanol as solvent Red raspberry UAE Fruit Anthocyanins S/F ratio 4:1 (ml/g) and 400 W UP Grapes UAE Fruit Flavonoids Water ethanol (50:50), extraction temperature ( K), UP and F, W and 24 khz Soybean MAE Beans Isoflavone 50% EtOH (25 ml), 500 Cortex fraxini MAE Bark Coumarins, flavones Hu Zhang (Rhizoma Polygoni Cuspidati) Vacuum MAE and MAE W MP at K temperature 1.0 g sample in 40 ml polyethylene glycol (PEG) solution, K temperature Leaves Resveratrol 95% methanol (40 ml), K temperature, MP 600 W, vacuum pressure (50 kpa) for VMAE Strawberry SFE Fruits Phenolic compounds Modifier: Ethanol (0% to 20%) with CO2. 60 min extraction time with a flow rate of 15 g/min, Tc ( K) at 5 MPa Pc Orange UAE Peel Flavonoids Ethanol:Water ratio 4:1 (v/v) at K and 150 W UP 25 min Higher yield rate than UAE and comparable recovery with 2 SE in short time. In SE, limited solvent choice 10 min UAE resulted in rapid and enhanced extraction of phenolic compounds by 4.23% as compared to 4 CSE techniques with reduced solvent and energy 15 min 40% less yield of flavonoid (isorhamnetin 3-O-glucoside), higher extract yield of reducing compounds as compared to CSE 60 min Excellent extraction efficiency than SE with more choices of solvent 200 s 78.13% recovery rate than 71.4% of CSE 6 min Higher recovery than conventional reference method 20 min Similar recovery rate in comparison with UAE but processing of 10 samples is possible simultaneously with MAE 10 min 96% recovery rate of extract yield, relatively higher than maceration and reflux extraction 15 min 6-9% increase in extract yield from VMAE than MAE and 5 RE 60 min Rapid extraction of total phenolics than CSE with minimum solvent usage 30 min 35% to 40% increase in phenolic compounds than CSE (Xiao and others 2008) (Briones-Labarca and others 2015) (Périno-Issartier and others 2011) (Londoño-Londoño and others 2010) (Chen and others 2007) (Carrera and others 2012) (Rostagno and others 2007) (Zhou and others 2011) (Wang and others 2008b) (Akay and others 2011) (Khan and others 2010) (Continued) 306 ComprehensiveReviewsinFoodScienceandFoodSafety Vol.16,2017 C 2017 Institute of Food Technologists

13 Table 3 Continued. Plant sample Red bayberry (Myrica rubra) Green extraction technique Plant matrix/part Target phenolic compound VMAE Leaves Myricetin 50% ethanol (40 ml), at K and 40 kpa, MP (600 W) Jabuticaba UAE Skin Anthocyanins Ethanol (99.5%) as solvent, S/F ratio 10:1 at K temperature and 81 W UP Canola SFE Press cake/ meal Hydroxy-cinnamic acid (Sinapine) Optimum extraction parameters Extraction time Remarks Reference 150 g canola press cake, modifier (95% ethanol) with CO2 at Tc KandPc 400 MPa, with flow rate of CO2 at 70 g/min Olive UAE Leaves Flavonoids 50% ethanol, sample/solvent ratio (500 mg dried leaf to 10 ml), UP 220 W and F50kHz Apple MAE Pomace Flavonoids MP (650.4 W), ethanol as solvent (62.1 ml) and S/F ratio (22.9:1) Wine grapes SFE Seeds Flavonoids and phenolic acids Rosemary MAE Dried leaves Phenolic acids and flavonoids 99.9% pure CO2 as solventattc/pc of 313 K/35 MPa to obtain SFE extracts at S/F ratio of g of sample in methanol as solvent (highest yields), MP: low (320 W for 1 min for flavonoids), high (800 W for 5 min for total phenolics) Wheat UAE Bran Flavonoids 64% ethanol at K in ultrasonic cleaning bath at 40 khz F and 250 W UP, respectively) Maritime pine SFE Bark Flavonoids (catechin and epicatechin) CO2 + Ethanol as solvent and modifier (10%, v/v), 30 MPa Pc, static extraction (10 min) and dynamic extraction (90 min) at Tc K 20 min Enhanced extraction of thermolabile phenolic compounds with better recoveries in shorter time periods than SE 120 min Rapid and maximum recovery of anthocyanin than traditional LPSE 60 min Reduced extract recovery of phenolic compound. Rapid and fast extraction in contrast to CSE 60 min Less consumption of time and solvent for comparable extract yields with conventional reference method 53.7 s Higher recovery rates than CSE, RE, and UAE techniques 240 min SFE has provided efficient recovery of phenolic compounds than those obtained by conventional distillation 5 min Comparable recoveries of both SE and MAE. MAE was better than UAE and SE with reduced consumption of solvent and time 25 min Similar or better recovery rate 90 min SFE extract yield is comparatively higher than that of hydro-distillation. Rapid and efficient recovery in shorter extraction time (Wang and others 2008b) (Santos and others 2012) (Li and others 2010) (ŞahinandŞamli 2013) (Bai and others 2010) (Prado and others 2012) (Švarc-Gajić and others 2013) (Wang and others 2008cc) (Braga and others 2008) (Continued) C 2017 Institute of Food Technologists Vol.16,2017 ComprehensiveReviewsinFoodScienceandFoodSafety 307

14 Table 3 Continued. Plant sample Green extraction technique Plant matrix/part Target phenolic compound Dittany of crete MAE Stem Phenolic compounds Grape bagasse (Piso) SFE Stems, skins and seeds Anthocyanins, catechins, glycosides of flavonols Apple PLE Pulp and peel Catechins, flavonols (quercetin) and anthocyanins Jabuticaba (Plinia cauliflora) Guava (Psidium guajava) Optimum extraction parameters Extraction time Remarks Reference Solvents (methanol, acetone, ethyl acetate, 20 ml of each) 750 W MP for 1 min 20 g of bagasse as feed material, CO2+ 96% ethanol 10% (w/w) as modifier at Tc (313 K), 2 extraction cycles at Pc 20 and 35 MPa with S/F ratio 80 and 115, respectively 99% methanol (solvent), K temperature, 7 MPa pressure PLE Skin Anthocyanins Extractor conditions: Pressure (5 MPa) and 553 K temperature MAE Leaves Flavonoids Ionic liquids (1-Butyl-3- methylimidazolium chloride ([bmim]cl), 1-butyl-3- methylimidazolium tetrafluoroborate ([bmim][bf4]) (20 ml of each ionic liquid) at K temperature Coffee SFE Grounds and husk Phenolic compounds Parsley(Petroselinum crispum) PLE Flakes (glycone of apiin and melonyl-apiin Pc of 20 MPa (husk) and 10 MPa (spent coffee), 4% and 8% ethanol (w/w) as solvents, Tc K (coffee husks) and K (coffee grounds) Temperature ( K), pressure (7 MPa), particle size (<850 µm), S/F ratio (250) and 75% flush volume 1 min MAE with acetone as solvent gives maximum yield of thermolabile polyphenols, better than CSE in short time intervals with less solvent consumption 300 min 20 MPa gives efficient, rapid, and enhanced recovery of phenolic compounds conventional SE extraction technique 5 min (static mode) 9 min (static mode) Comparable recovery with reduced solvent amount, handling, and time required than CSE Higher recovery: 2.15-fold anthocyanins (13%) and 1.66-fold (8%) total phenolic compounds than CSE at lower temperature 10 min Efficient extraction of phenolic compounds with relatively excellent absorbing abilities of IL solutions used for MAE process as compared to traditional reflux extraction 60 min (husk), 60 min (spent coffee) Static extraction (5 min) High extract yield, that is, 15 ± 2% for spent coffee grounds with ethanol and 3.1 ± 4% for coffee husks by SFE for phenolic compounds Improved recovery of 6 phenolic compounds with wider solvent choice without any thermal degradation (Proestos and Komaitis 2008) (Farías-Campomanes and others 2013) (Alonso-Salces and others 2001) (Santos and others 2012) (Du and others 2009) (Andrade and others 2012) (Luthria 2008) (Continued) 308 ComprehensiveReviewsinFoodScienceandFoodSafety Vol.16,2017 C 2017 Institute of Food Technologists

15 Table 3 Continued. Plant sample Green extraction technique Plant matrix/part Target phenolic compound Apple PLE Pulp and peel Catechins, flavonols (quercetin) and anthocyanins Optimum extraction parameters Extraction time Remarks Reference 99% methanol (solvent), K temperature, 7 MPa pressure Cabbage (Red) PHWE Leaves Anthocyanins 2.5 g (sample), K at 5 MPa solvent ratio: water/ethanol/formic acid (94:5:1, v/v/v). Bitter melon (Momordica charantia) Citrus (Citrus unshiu) PHWE Fruit Chlorogenic acid, genistic acid and catechin PHWE Peel Flavanones (hesperidin and narirutin) Methanol as solvent at 5 MPa and K with 2 ml/min of flow rate 1 cycle of PHWE at K temperature and MPa pressure 5 min (static mode) Comparable recovery with reduced solvent amount, handling and time required than CSE 7 min Fast recovery and identification of polyphenols coupling with HPLC-DAD 120 min Faster and high yield in short time (2 h) as compared to SE (6 h) 10 min High yield Hesperidin (3.2 fold) Narirutin (3.7 fold) than CSE (Alonso-Salces and others 2001) (Arapitsas and Turner 2008) (Budrat and Shotipruk 2009) (Cheigh and others 2012) 1 MP (Microwave Power). 2 SE (Soxhlet Extraction). 3 UP (Ultrasonic Power). 4 CSE (Conventional Solvent Extraction). 5 RE (Reflux Extraction). 6 S/F (Solvent-to-feed ratio). 7 F (Frequency). 8 Tc (Critical temperature). 9 Pc (Critical pressure) C 2017 Institute of Food Technologists Vol.16,2017 ComprehensiveReviewsinFoodScienceandFoodSafety 309

16 Figure 5 Operational schematic principle and mechanism of pressurized liquid extraction (PLE) system. solvents alone; for example, isopropanol and ethanol (Luthria and others 2007; Mustafa and Turner 2011). Matrix characteristics. The analyte recovery rate and extraction efficiency of PLE is also affected by plant matrix characteristics. Prominent factors in this regard include the nature of target compounds, the relative bonding behavior of the analyte with the binary extraction solvent, and the particle size distribution and moisture contents of botanical samples. These factors can affect the PLE selectivity, thereby subsequently affecting extraction efficiency and recovery rates of phenolic compounds from matrices (Mustafa and Turner 2011). Molecule bonding behavior during solvation is affected by matrix moisture contents, which are unique to every plant. The characteristic particle size of matrix molecules affects the final extraction yields of targeted components by influencing mass transfer rate and extraction kinetics from various foodstuffs or herbal preparations (Carabias-Martínez and others 2005). Extraction time and temperature. Operational conditions of temperature and pressure also significantly influence PLE selectivity and efficiency. As PLE involves use of elevated temperatures under reduced pressure, the use of thermal energy helps to disrupt the matrix structure by overcoming molecular bonding forces (Luthria 2008). Targeted phenolic compounds are present in bound form in the sample matrix, and elevated temperatures are used to decrease activation energy to overcome the interactive forces (cohesive and adhesive) between matrix and solvent molecules to bring about desorption. After wetting of the plant matrix is achieved by solvation, elevated temperatures result in minimized surface tension between samples, solvent, and solute interfaces during PLE. This reduction in surface tension causes formation of solvent cavities that permit dissolution of analyte in the solvent. The elevated temperature also improves extraction efficiency by decreasing extractant viscosity, which leads to improved penetration inside the sample matrix (Wang and Weller 2006). Application of high pressure is, however, reported to exacerbate the problems associated with air-bubbling during the extraction process, which can lead to low solubility rates (Carabias-Martínez and others 2005; Mustafa and Turner 2011). PLE applications for the green extraction of polyphenols A survey of the literature suggests that PLE has been gaining popularity during the last couple of years as a green method for polyphenol extraction from herbal preparations. This increasing trend is attributed to PLE automation, which allows extraction in shorter time intervals with a minimum solvent and sample pretreatment requirements (Garcia-Salas and others 2010; Mustafa and Turner 2011). PLE has been successfully employed for optimal extraction of anthocyanins from freeze-dried red grape skin using acidified water as a solvent. Among 6 solvents, acidified methanol was found to provide maximum recovery rates of anthocyanins and total phenolics in extracts obtained by PLE at K temperature and 10.1 MPa pressure. The results show a considerable decrease in the consumption of solvent and a total extraction time of 3 min compared with the 20 min for SE. PLE at elevated temperature has proved to be an efficient eco-friendly technique for the extraction of anthocyanins and total phenolics from red grape skin (Ju and Howard 2003). PLE has also been optimized in order to gain a substantial recovery of polyphenols from apple peel and pulp. In this study, the extraction of total phenolics content was optimized using different process variables (solvent, pressure, temperature, and static time). Optimized conditions for maximum polyphenol recovery were reported to be pure methanol as extractant at K temperature and 7 MPa pressure for 5 min under static mode. In conclusion, the efficiency of PLE as a green technique for extraction of polyphenols was found to be comparable with CSE, with reduced consumption of solvent volumes (20 to 40 ml for 2 extraction cycles) and with less time required for sample preparation (Alonso-Salces and others 2001). The skin of Jabuticaba, a Brazilian native plant, has been reported to be a rich source of anthocyanins and antioxidants. An 310 ComprehensiveReviewsinFoodScienceandFoodSafety Vol.16,2017 C 2017 Institute of Food Technologists