P U B L I C A T I O N S CODON Italian Journal of Food Science, 2023; 35 (3): 17–43 ISSN 1120-1770 online, DOI 10.15586/ijfs.v35i3.2298 17 P U B L I C A T I O N S CODON Content of selected polyphenolic substances in parts of grapevine Lenka Jurasova1†*, Tunde Jurikova2†, Mojmir Baron1, Jiri Sochor1 1Department of Viticulture and Enology, Faculty of Horticulture, Mendel University in Brno, Lednice, Czech Republic; 2Institute for Teacher Training, Faculty of Central European Studies, Constantine the Philosopher University in Nitra, Nitra, Slovakia †These authors shared first authorship. *Corresponding Author: Lenka Jurasova, Department of Viticulture and Enology, Faculty of Horticulture, Mendel University in Brno, Valticka 337, 691 44 Lednice, Czech Republic. Email: xjurasov@mendelu.cz Received: 7 November 2022; Accepted: 30 March 2023; Published: 18 July 2023 © 2023 Codon Publications OPEN ACCESS REVIEW Abstract This review provides an overview of the variety of occurrences, content, extraction and health effects of selected polyphenolic compounds associated with different parts of grapevine (seeds, peel, pulp and stems). The review provides a brief characterisation of grape parts, the content of polyphenolic compounds and their extraction together with their graphical forms of presentation and diversity as determined by different studies. The content of individual polyphenolic compounds differed with studies. Effects of different factors were evident in both grow- ing style and geographical location of vineyards as well as extraction methods and analytical conditions. Keywords: grapevine, peel, polyphenolic compound, seed, skin, stem Introduction The aim of the review was to summarize the occur- rence, distribution and determination of polyphenolic compounds in different parts of grapes. The review also demonstrated variations in the values of polyphenolic compounds with respect to the methods used as well as variations within varieties. The polyphenolic compounds were selected based on the literature. Among the most studied polyphenolic compounds in grapes are catechin, epicatechin gallate, quercetin, resveratrol and gallic acid (GA). Owing to its simple structure among other factors, GA represents the most commonly used standard for determining total polyphenolic compounds. The aim of creating a com- parative table was to focus on the current literature. The analytical methods used were listed for each compound. However, in the case of some less usual analytes, older sources (from 2003 onwards) were also used. For the purpose of clarity and to emphasise the diversity of indi- vidual results, all mass concentrations were converted to a common unit of µg/g. For determining concentration in solution, the units were changed to µg/mL. Moreover, this review considered polyphenols in accordance to their distribution in grapes reflecting their health benefits. Polyphenolic compounds found in grapes, their distribution and health benefits Polyphenols are a class of compounds comprising one or more phenolic hydroxyl groups bonded to at least one aro- matic ring (Di Lorenzo et al., 2021). The majority of poly- phenolic compounds are generated from phenylpropanoid and phenylpropanoid acetate pathway and represent 40% of organic carbon in plants. Classification of phenolic compounds is based on different approaches according mailto:xjurasov@mendelu.cz 18 Italian Journal of Food Science, 2023; 35 (3) Jurasova L et al. stilbenes, tannins, lignans, lignins, monolignols, antho- cyanins, isoflavones, chalcones, naphthoquinones and anthraquinones, and diarylheptanoids. As observed, phe- nol sorting is not dogmatic, and it depends, in particular, on the purpose of dividing them (Brenes et al., 2016). The distribution of polyphenols within a grape bunch is different as shown in Figures 1–4. The content, abundance and distribution of polypheno- lic compounds in grapevines are highly dependent on the geographical and climatic conditions, grape variety, cultivation processes and the stage of ripeness. However, there is no doubt that Vitis vinifera is one of the most important sources of polyphenolic substances, espe- cially wine industry wastes (grape skin, stems and seeds), which represent 20% of the weight of processed grapes (Teixeira et al., 2018) and therefore are a matter of grow- ing interest and emphasis for farmers. As mentioned above, the concentration of polyphenols varies not only between plant species but also between plant parts. Thus, in the following sections, seeds, peels, to the functional group bound to phenol or the number of phenolic units found in the molecule, and this differs mainly according to studies. The easiest division of pheno- lic compounds is into flavonoids, the most studied group, and non-flavonoids. Nowadays, phenolic compounds are classified into groups and subgroups based on the number of phenolic rings and structural elements attached to the rings (Butterfield, Castegna, Lauderback,  & Drake et al., 2002). According to this approach, the major classes rep- resent phenolics, flavonoids, stilbenes and lignans (Pietta et al., 1998). The group of flavonoids, as the most abun- dant class in grapes or wine, can be represented by flava- nols, flavones, flavanonols and anthocyanins (Nollet and Gutierrez-Uribe, 2018; Teixeira et al., 2018; Tsimogiannis and Oreopoulou, 2019). Depending upon products (Nollet and Gutierrez-Uribe, 2018; Teixeira et al., 2018; Tsimogiannis and Oreopoulou, 2019), flavanols, flavones, flavanonols and anthocyanins belong to a group of flavonoids, and are the most abun- dant polyphenols present in grapes or wine and related products. Other explanation divided polyphenolic into the following sub-classes: coumarins, furanocoumarins Cabernet Sauvignon V3 Cabernet Sauvignon V2 Cabernet Sauvignon V1 Cabernet Sauvignon (SB) Cabernet Sauvignon (SA) Frankovka (SA) Frankovka (SB) Prokupac (SB) Prokupac (SA) Merlot (SB) Merlot (SA) Black Tamjanika (SB) Black Tamjanika (SA) Zăcinak (SB) Zăcinak (SA) Gamay (SB) Gamay (SA) Župljanka (SB) Župljanka (SA) Bagrina (SB) Bagrina (SA) Chardonnay (SB) Chardonnay (SA) 0 4 8 12 16 20 24 Figure 1. Graph shows the values of total polyphenols by using Folin’s reagent in seeds. Values are expressed in milligram of GA equivalent to per gram of seeds, except for Silva et al. (2018), where the equivalent is epicatechin gallate. The same colour shows the measurements of one research group. Next to each bar is the description indicating the variety used for measure- ments. SA: solvent A; AcEtOH: acidified aqueous ethanol; SB: solvent B; ChCit: choline chloride:citric acid; I: irrigation; LR: leaf removal. Light blue (Castro-Lopez et al., 2019), purple (Dabetić et al., 2020), green (Chorti et al., 2016), yellow (Dinis et al., 2020), grey (Radovanović et al., 2019), orange (Silva et al., 2018) and dark blue (Pantelić et al., 2016). Italian Journal of Food Science, 2023; 35 (3) 19 Content of selected polyphenolic substances in parts of grapevine pathogens. Other phenols have a mechanical function and are pollinator attractants, adsorb ultraviolet (UV) rays and reduce the growth of surrounding competitive plants. Polyphenols could have a negative allelopathic effect if released from the leaves, roots or decomposing plant tissues. To compete with surrounding plants for water, sunlight and minerals, plants release phenols that may inhibit the growth of adjacent plants. This effect could possibly be utilised in the production of genetically mod- ified plants that produce compounds with allelopathic effects to eradicate weeds (Crozier et al., 2008; Novak et al., 2008; Taiz et al., 2015). Polyphenolics played an important role in overcoming the challenges of water- to-land transition. As an example, the evolution of phen- ylpropanoid pathway in primitive terrestrial plants and algae helped them to adapt to exposition to UV radia- tion even before transition to land. This pathway leads to the production of more than 5,000 compounds called flavonoids. The land ecosystem means decline of water pulp and stems are described separately. The most abun- dant group of polyphenols found in grapes are flavanols, represented by simple monomers of catechin and epicat- echin gallate, oligomeric proanthocyanidins (OPCs; 2–5 units), and condensed tannins (polymers of more than five phenolic units), mainly present in the pulp (Crozier et al., 2008). The most abundant form of flavanol group is catechin, mainly found in grape skin and seeds, and traces of monomers or dimers are discovered in grape pulp. The phenolic hydroxyl group is relatively acidic com- pared with other hydroxyl groups because of its bond to the aromatic ring, causing deprotonation of the oxygen substituent and stabilisation of the complex. It causes reactivity and determines phenols as the building blocks of polymers, such as lignins or suberins, as well as their involvement in the production of wide spectra of com- pounds in plants. Owing to their chemical variety, poly- phenols have different functions in plants. Many of them are involved in providing defence against herbivores and Figure 2. Graph shows the values of total polyphenols by using Folin’s reagent in grape peel. Values are expressed in milli- gram of GA equivalent to per gram of peel. The same colour shows the measurements of one research group. Below each bar is the description indicating the variety used for measurements. SA: solvent A; AcEtOH: acidified aqueous ethanol; SB: solvent B; ChCit: choline chloride:citric acid; P1-10: samples from Piranshahr city; S1-10: samples from Sardasht city. Purple (Dabetić et al., 2020), light blue (Castro-Lopez et al., 2019), pink (Singha and Das, 2015), black(Ni et al., 2017), dark blue (Radovanović  et  al., 2019), light green (Khoshamad et al., 2020), dark green (Chorti et al., 2016), yellow (Dinis et al., 2020), grey (Radovanović et al., 2019), red (Baiano and Terracone, 2012) and orange (Silva et al., 2018) Agiorgitiko I and LR Agiorgitiko LR Agiorgitiko - irrigation Agiorgitiko Cerceal white Vranac Merlot Touriga Nacional Preto Martinho Pinot Gris Chardonnay Welschriesling Sauvignon Blanc Petra Riesling Prokupac Pinot Noir Shiraz Sangiovese Cabernet Franc Merlot Cabernet Sauvignon 0 50 100 150 200 250 300 350 400 TPC (mg/g) 20 Italian Journal of Food Science, 2023; 35 (3) Jurasova L et al. Cabernet Sauvig.. Cabernet Sauvig.. Frankovka (SB) Frankovka (SA) Prokupac (SB) Prokupac (SA) Merlot (SB) Merlot (SA) Black.. Black.. Zăcinak (SB) Zăcinak (SA) Gamay (SB) Gamay (SA) Župljanka (SB) Župljanka (SA) Bagrina (SB) Bagrina (SA) Chardonnay (SB) Chardonnay (SA) Cabernet.. Cabernet.. Cabernet.. Red globe Kichmich chorni Flame seedles Thompson seedles Kyoho grape Pinot Gris Chardonnay Welschriesling Sauvignon Blanc Petra Riesling Prokupac Pinot Noir Shiraz Sangiovese Cabernet Franc Merlot Cabernet.. S10 S9 S8 S7 S6 S5 S4 S3 S2 S1 P10 P1 P2 P3 P4 P5 P6 P7 P8 P9 0 5 10 15 Figure 2. Continued. Italian Journal of Food Science, 2023; 35 (3) 21 Content of selected polyphenolic substances in parts of grapevine Agiorgitiko irrigation and LR Agiorgitiko - leaf removal (LR) Agiorgitiko - irrigation Agiorgitiko Cerceal white Vranac Merlot Thompson seedless Beogradska basemena Touriga Nacional Preto Martinho 0 15 30 45 60 75 TPC(mg/g) Figure 2. Continued. sources, resulting in the formation of a group of sub- stances called suberins. These are polymers of phenolic (hydrophilic) and aliphatic (hydrophobic) groups import- ant in forming periderm in the root and bark because they provide a hydrophobic barrier and prevent water loss. Suberins are the main component of the cork and provide physical barrier against pests. Lignin is a trimer from monolignol monomers that toughen cellulose fibres in specialised cell wall structures in tracheids and vessels. These structures allow the carrying of plant’s weight on land, which is not required in the aquatic environment, and transportation of water and minerals from the roots to all plant tissues. Lignin formation helped plants to overcome the pull of gravity and compete for sunlight with other plants (Novak et al., 2008; Taiz et al., 2015). Last but not least, in addition to many changes, chal- lenges and problems, plants were exposed to a new spectrun of pathogens and herbivores. To deal with this challenge, different subgroups of phenolics that mediate chemical defence, and thus have antiherbivorous, insec- ticidal and allelopathic (interaction) effects and prevent the spread of fungi and bacteria, were evolved. Owing to their toxicity, phenolic metabolites do not occur in the form of free aglycones but are conjugated with cell wall components or generate conjugated glycosides (GL). In addition to the toxic effects, phenols are responsible for the colour, aroma, taste and antioxidative properties of plant organs (War et al., 2012). Grapes and their products have displayed a wide range of utilisation. Grape by-products have been used for feeding agriculturally important animals with different results. The feeding of chickens by grape pomace and seed extracts led to improvement in growth in a study conducted by Liu et al. (2014). On the other hand, no significant increase in the growth was observed in chick- ens fed with grape seed extracts (GSE) and grape pomace (Brenes et al., 2016; Chamorro et al., 2015). A positive boost in growth could be explained due to vari- ous reasons. GSE inhibits growth of the pathogen causing coccidiosis oxidative stress (Wang et al., 2008), reduces meat lipid oxidation (Brenes et al., 2016; Iqbal et al., 2015) and increases the abundance of polyunsaturated fatty acids in poultry meat (Chamorro et al., 2015). Other studies showed a significant effect on pigs’ metabolism after the feeding of grape marc meal or grape pomace. Intake of grape by-products improved nitrogen metab- olism and growth, modified fatty acid patterns in sub- cutaneous fat (Yan and Kim, 2011), and increased feed conversion ratio and antimicrobial effect on Escherichia Coli in the faeces of weaned pigs after feeding with grape by-product (Fiesel et al., 2014). In contrast, no effect on the growth of rabbits was observed (Nicodemus et al., 2007; Tortuero et al., 1994). Moreover, in the study conducted by Ferreira et al. (1996), feeding rabbits with grape pomace led to a decrease in feed conversion ratio. No change in the production or composition of milk was observed in case of dairy cows fed with grape pomace or marc (Eleonora et al., 2014; Hansen and Nielsen, 2004). However, Moate et al. (2014) described an increase of monosaturated fatty acids, polysaturated fatty acids and linoleic acid in milk after feeding cows with ensiled or dried grape marc. Feeding with grape marc decreased weight gain in beef cattle (Manterola et al., 1997), and the presence of lignin, tan- nin and fibre decreased nutrients’ digestibility in fatting lambs after feeding them with grape pomace (Eleonora et al., 2014). In contrast, Abarghuei et al. (2010) showed a positive effect on retained nitrogen and ruminal parameter in sheep fed with grape pomace. Numerous experiments confirmed the use of grape by-products as a nutrient for farm animals. Different effects of feeding grape by-products are caused due to different production processes used in wineries, affecting the quality of grape by-products, and also variations among cultivars (Gierus et al., 2020; Milder et al., 2005). 22 Italian Journal of Food Science, 2023; 35 (3) Jurasova L et al. Cerceal white Thompson seedless Beogradska besemena S10 S9 S8 S7 S6 S5 S4 S3 S2 S1 P10 P1 P2 P3 P4 P5 P6 P7 P8 P9 0 2 4 6 8 10 12 14 TPC [mg/g] Red globe Pinot Gris Chardonnay Welschriesling Sauvignon Blanc Petra Riesling Prokupac Pinot Noir Shiraz Sangiovese Cabernet Franc Merlot Cabernet Sauvignon Kichmich chorni Flame seedles Thompson seedles Kyoho grape 0 100 200 300 400 500 600 700 TPC [mg/g] Figure 3. Graph shows the values of total polyphenols by using Folin’s reagent in grape pulp. Values are expressed in milli- gram or microgram of GA equivalent to per gram of pulp. The same colour shows the measurements of one research group. Below each bar is the description indicating the variety used for measurements. P1-10: samples from Piranshahr city; S1-10: samples from Sardasht city. Yellow (Dinis et al., 2020), red (Baiano and Terracone, 2012), green (Khoshamad et al., 2020), pink (Singha and Das, 2015), black (Ni et al., 2017) and blue (Pantelic et al., 2016). Italian Journal of Food Science, 2023; 35 (3) 23 Content of selected polyphenolic substances in parts of grapevine Vranac Merlot Moscatel Viosinho Fernão Pires Malvasia Fina Rabigato Austrian vine Slovak vine White vine red vine Touriga Nacional Preto Martinho 0 25 50 75 100 125 150 75 200 225 250 TPC (mg/g) Figure 4. Graph shows the values of total polyphenols by using Folin’s reagent in grape stems. Values are expressed in milli- gram of GA equivalent to per gram of stems, except for Silva et al. (2018), where the equivalent is epicatechin gallate. The same colour shows the measurements of one research group. Below each bar is a description indicating the variety used for mea- surements. Grey (Radovanović et al., 2019), green (Leal et al., 2020), yellow (Hanušovský et al., 2020), blue (Domínguez-Perles et al., 2014) and orange (Silva et al., 2018). Polyphenolic compounds of grape seeds, distribution, extraction and health potential Grape seeds are pear shaped with a trigone transverse section. The seeds are composed of a cuticle, an epi- dermis and two integuments going around the albumen and the embryo (Cadot et al., 2006). Development of the seed and fruit are related. Their maximum fresh weight (fw) occurs during colouring of berries, while maximum dry seed weight coincides with maximum berry weight (Ristic and Iland, 2005). Colour of seeds varies from green to dark brown during maturation (Kennedy et al., 2000). Change of colour, along with hardening, is con- comitant with the oxidation of phenolics and maturing of the bunch (Cadot et al., 2006). Grape seeds are composed of fibre (40%), volatile oils (16%), protein (11%), polyphenolic compounds (7%) and other substances (sugars, minerals etc.; de Campos et al., 2008). Within the grapes, soluble phenols are distributed unevenly, with dominant representation in seeds (70%), 28–35% found in skins and, in spite of their large volume, the least presence of 10% is found in pulp. Supported by various studies (Cheng et al., 2012; Makris et al., 2007), total polyphenols are maximum in seeds among different analysed grape components in different vine varieties. Catechin and epicatechin gallate are the most abundant phenolic compounds present in the seeds and stems. Within flavonols, the main representative phenol is rutin (Cheng et al., 2012; Makris et al., 2007). Presence of dif- ferent phenols is affected by genetic diversity between varieties, regions, light intensity, soil compositions, climatic and agronomic conditions, ripening stages, processes of extraction and storage conditions (de la Cerda-Carrasco et al., 2015; Jordão et al., 2001; Nassiri- Asl and Hosseinzadeh, 2009). Presence of the most abundant oligomers is different between plant compositions. The major oligomer found in the seeds, according to different studies, is procyani- din B2. On the other hand, procyanidin B1 is reported to be the dominant oligomer in the skin and bunch stems (Dwyer et al., 2014; Topalovic and Mikulic-Petkovsek, 2010; Vujasinović et al., 2021). Despite differences, the studies showed the highest content of polphenols in the following order: the highest concentration was in the seeds followed by the berry skins and must (mustum or young wine) (Boso et al., 2019). Antioxidant activity of grapes was confirmed by 1,1-Diphenyl-2-picrylhydrazyl (DPPH) and 2,2’- azino- bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, where the highest was found in seed extracts, fol- lowed by stem and skin extracts. The higher antioxidant capacity of the seeds may correlate with its higher total phenolic content (TPC), supported by previous results that phenols, dominantly found in the seeds, possess antioxidant activity. 24 Italian Journal of Food Science, 2023; 35 (3) Jurasova L et al. Surprisingly, a negative correlation between the content of phenolics and EC50 describing antioxidant activity was proven by Wen et al. (2016), suggested that among phenolics, antioxidant activity is the combined effect of phenolic compounds, sterols and vitamin E. On the other hand, a negative relationship was observed between the quantity of tocols and the content in total phenol (Vujasinović et al., 2021). Extraction of grape polyphenols in the seeds is dependant upon two conditions, dissolution of concrete polyphe- nolic compounds in the plant material matrix, and their diffusion in the external solvent medium. Ethanol as an extracting solvent was shown to be an efficient method of extracting polyphenol. Nawaz et al. (2006) studied different conditions of extraction of polyphenols from grape seeds using 50% ethanol and 50% water as solvents. When com- pared with a GA standard, extraction of grape seed poly- phenols with a 0.2-g/mL solid to liquid ratio, double-stage extraction, and 0.22-m pore size membrane seem to be the most optimal conditions (polyphenols represents 11.4% of the total seeds weight). In respect of concrete polyphenols, it mostly depends on the applied method. As an example, monomeric procyanidins are found in large amounts in grape seeds, but the quantity of extraction is low due to their low water solubility. Therefore, methods utilising solvents with lower polar- ity (Soxhlet, supercritical fluid extraction (SFE) and ethanol-assisted extraction) are preferred to increase extractability (Colibaba et al., 2015). In their findings, the choice of solvent used for extraction and the effect of extraction were supported by the Teixeira group, who tested three different solvents and three different methods for extraction. Specifically, Soxhlet, ultrasound extraction, and maceration were performed, and meth- anol, ethanol and, acetone with different polarities were used as solvents, with the highest TPC using 70% ace- tone, followed by 70% ethanol extract and 70% methanol extract. However, comparable results were obtained with different extraction methods (Teixeira et al., 2014). Extraction efficiency does not only depend on the selec- tion of the solvent but also on the extracted phenolic compound. The utilisation of ethyl acetate for extraction showed a large recovery effect on flavonols, whereas methanol was the preferred solvent for flavan-3-ol (catechin, epicatechin gallate and epigalocatechin) extraction. Owing to the low permeability of tissues to non-polar aprotic solvents, addition of water to the solvent increases process efficiency. As an example, the efficiency of proanthocyanidin extraction was signifi- cantly increased by adding water to acetone or ethyl acetate. Moreover, the type of analysed material influ- ences measured concentrations because of the relation between the number and weight of seeds, and weight and stage of berry ripening. For example, the highest content of catechin is at grape veraison; then the con- centrations decrease until near maturity (Downey et al., 2003; Freitas and Glories, 1999; Kennedy et al., 2000). Also, decline of monomeric flavanols is more rapid than oligomers because of increasing polymerisation during maturity. Many positive effects of polyphenolic compounds extracted from seeds have been described for human health, especially their ability to decrease the occurrence of heart disease. Polyphenols mostly contribute to lower the oxidation levels of low-density lipoprotein cholesterol and blood pressure, enhance the functioning of endo- thelium, reduce inflammation and platelet aggregation, and decrease cell senescence by inhibiting novel pro- teins activating this process (Dohadwala and Vita, 2009; Moreno et al., 2003; Shi et al., 2003). Grape seed extracts, through their inhibition of enzymes lipoprotein lipase and pancreatic lipase involved in fat metabolism, could be utilised as a dietary supplement to limit fat absorp- tion and fat accumulation in tissues (Bagchi et al., 2000). Intake of grape extracts by mice resulted in reducing myocardial injury and myocardial ischemia- reperfusion and decrease of superoxide anion production as well as platelet adhesion and aggregation (Bagchi et al., 2000; Karthikeyan et al., 2007; Olas et al., 2008). In addition, procyanidins from GSEs have demonstrated inhibition of thrombus formation in mice after oral and intravenous administration (Sano et al., 2005). Moreover, Anastasiadi et al. (2012) proved that extracts having abundance of flavonoids and its derivatives from grape seeds, along with the occurrence of phenolic acids, stilbenes and flavonoids from grape stems, possess anti- microbial properties. The antimicrobial activities of sev- eral non-flavonoid phenolic compounds from wine were tested, and vanillic and GA exhibited inhibitory effects towards K. pneumoniae and E. coliand (Vaquero et al., 2007). It has been demonstrated that extracts from red grape seeds inhibit the growth of important human pathogens, such as E. coli, Candida albicans, Listeria monocytogenes and Salmonella typhimurium. Moreover, proanthocyanidins are indicated as dominant com- ponents in the protective prevention of inflammation mediated through the reduction of Faecalibacterium prausnitzii in the intestinal lumen, leading to the block- ade of inflammatory response cascade in the gut. In the central nervous system of mice, the beneficial effects of GSE to modulate lipid peroxidation and oxi- dative damage of DNA bases were observed (Balu et al., 2006; Feng et al., 2005; Teixeira et al., 2014). For the above-mentioned reasons, a growing interest is observed in the use of grape seeds, and because the Italian Journal of Food Science, 2023; 35 (3) 25 Content of selected polyphenolic substances in parts of grapevine Table 1. Comparison of concentrations of selected major polyphenolic compounds presented in grapevine seeds according to studies. Analyte Concentration (µg/g or % w/w*) Analytical method Concentration in Studies Gallic acid 10,580–105,000 HPLC/DAD Dry weight Cotea et al. (2018) 300–6,700 HPLC/UV-VIS Residue Silva et al. (2018) 3,130–3,210 HPLC/DAD Dry weight Radovanović et al. (2019) 745–2,450 HPLC/DAD Dry weight Dabetić et al. (2020) 310–270 HPLC/DAD Extract Aybastier et al. 2018 0.02–2.06* HPLC/DAD Extract Nakamura et al. 2003 210–1,250 HPLC/PDA Dry weight Bucić-Kojić et al. (2009) 4,000 HPLC/DAD/QMS Extract Chamorro et al. (2012) Catechin 820 HPLC/DAD Dry weight Cotea et al. (2018) 7,700–17,200 HPLC/UV-VIS Residue Silva et al. (2018) 456.66–823.90 HPLC/MS/QTOF Dry weight Boso et al. (2019) 7,620–8,080 HPLC/DAD Dry weight Radovanović et al. (2019) 2,911–15,587 HPLC/DAD Dry weight Dabetić et al. (2020) 1,360 HPLC/DAD Extract Aybastier et al. (2018) 1.03–4.93* HPLC/DAD Extract Nakamura et al. (2003) 1,790–6,640 HPLC/PDA Dry weight Bucić-Kojić et al. (2009) 8,000 HPLC/DAD/QMS Extract Chamorro et al. (2012) 674–1,418 HPLC/DAD Dry weight Iacopini et al. (2008) Epicatechin gallate 11,200–25,500 HPLC/UV-VIS Residue Silva et al. (2018) 429.86–445.20 HPLC/MS/QTOF Dry weight Boso et al. (2019) 10,340–10,600 HPLC/DAD Dry weight Radovanović et al. (2019) 948–6,269 HPLC/DAD Dry weight Dabetić et al. (2020) 790–6,200 HPLC/PDA Dry weight Bucić-Kojić et al. (2009) 8,000 HPLC/DAD/QMS Extract Chamorro et al. (2012) 472–2,057 HPLC/DAD Dry weight Iacopini et al. (2008) Trans-resveratrol 3,940–4,990 HPLC/DAD Dry weight Cotea et al. (2018) 7.11–37.93 HPLC/DAD Dry weight Silva et al. (2018) Ferulic acid 11,210–16,290 HPLC/DAD Dry weight Cotea et al. (2018) 3,100–11,800 HPLC/UV-VIS Residue Silva et al. (2018) Procyanidin B1 420–1,410 HPLC/DAD Dry weight Cotea et al. (2018) 97.75–106.27 HPLC/MS/QTOF Dry weight Boso et al. (2019) 0.7–1.73* HPLC/DAD Extract Nakamura et al. (2003) 6,000 HPLC/DAD/QMS Extract Chamorro et al. (2012) Procyanidin B2 310–670 HPLC/DAD Dry weight Cotea et al. (2018) 141.92–149.00 HPLC/MS/QTOF Dry weight Boso et al. (2019) 7,600–7,860 HPLC/DAD Dry weight Radovanović et al. (2019) 0.66–1.54* HPLC/DAD Extract Nakamura et al. (2003) 450–5,670 HPLC/PDA Dry weight Bucić-Kojić et al. (2009) 5,000 HPLC/DAD/QMS Extract Chamorro et al. (2012) Vanillic acid 5,360–13,020 HPLC/DAD Dry weight Cotea et al. (2018) 500–1,500 HPLC/UV-VIS Residue Silva et al. (2018) (continues) 26 Italian Journal of Food Science, 2023; 35 (3) Jurasova L et al. Table 1. Continued. Analyte Concentration (µg/g or % w/w*) Analytical method Concentration in Studies Epicatechin gallate 13,880–15,500 HPLC-DAD Dry weight Radovanović et al. (2019) 20–80 HPLC/PDA Dry weight Bucić-Kojić et al. (2009) 2,000 HPLC/DAD/QMS Extract Chamorro et al. (2012) Rutin 6.74–9.37 HPLC/DAD Dry weight Szabó et al. (2021) HPLC: high-performance liquid chromatography; DAD: diode-array detection; PDA: photodiode array; QMS: quadrupole mass spectrometry; MS: mass spectrometry; QTOF: quadrupole time of flight. highest phenolic content is found in seeds, production of grape seed oil (GSO) is increasing. Consumption of GSO is reported to be beneficial to health, especially because of its high content of phenolic compounds, unsaturated fatty acids, pigments, tocopherols and low cholesterol. In spite of relatively small presence of the mentioned compounds, GSO has been determined as a food supplement with con- siderably positive health effects. GSO and its components show health protective effects from antiradical, antioxi- dant and vitamin activity to a high metabolic value in the body (Assumpção et al., 2016; Fernandes et al., 2013). Bioactive anticancer, antimutagenic and anti-lipid effects and reduction in the risk of cardiovascular diseases qual- ify GSO to be used as a supplement in food and phar- maceutical industries (Garavaglia et al., 2016; Shinagawa et al., 2015). Comparing GSO of red and white grapes, on average, higher content of phenolic compounds was found in GSO from red varieties, with the highest con- tent found in the Hamburg variety (336.3 ± 4.8 μg/g) in accordance with the study conducted by Vujasinović et al. (2021), declaring higher content of phenols in GSE. Figure 1 shows that in spite of using the same analytical method (values of total polyphenols), the results of indi- vidual studies vary widely. Table 1 shows the content of individual polyphenolic components monitored in grape seeds, depending on the analytical method used. The results of individual studies are different. These dif- ferences are due to the choice of the solvent, the standard used, different laboratory conditions, different maturity conditions, and characteristics of different varieties from different locations. An overview of the most abundant polyphenolic compounds in grape seeds—their content and extraction Gallic acid Gallic acid, as one of the most representative phenolic compounds, was analysed by Cotea et al. (2018) using different extraction methods, attaining more than the 10th of dry weight (dw) in the Fetească neagră variety. The content of GA varies from 10.58 mg/g of dw using Soxhlet extraction to 105 mg/g of dw using the subcrit- ical water extraction method. The use of 75% ethanol for extraction is more effective in comparison to water. Additionally, higher pressure (15 bar) was significantly more effective than using 3-bar pressure. Bucić-Kojić et al. (2009), Chamorro et al. (2012), Dabetić et al. (2020) and Radovanović et al. (2019) measured significantly lower concentrations of GA related to dry weight. Radovanović et al. (2019) reported concentrations of 3.21 and 3.13 mg of GA in g of dw extracted ultrasoni- cally for 1 h with 40 mL of solvent system consisting of methanol:acetone:water:acetic acid mixture in the ratio of 30:42:27.5:0.5. Dabetić et al. (2020) described the impact of using different solvents for extraction—acidi- fied aqueous ethanol (AAE), green solvent (GS) and cho- line chloride:citric acid (ChCit). Aybastıer et al. (2018) investigated the effect of addition of 10 M HCl in a meth- anol:water extraction composition with no significant differences. Nakamura et al. (2003) compared concentra- tions of GA in different health foods containing GSE, and obtained different concentrations of GA. Bucić-Kojić et al. (2009) discovered that 50% ethanol was more efficient for GA extraction than 70% or 96% strength. Catechin A high range of concentration, that is, 7,700–17,200 μg/g in residue was found by Silva et al. (2018). Dabetić et al. (2020) tested extraction with GS and compared it with AAE. It was observed that for each variety, the extraction reagents were effective in different manners. The low- est concentrations were found for the Gammay variety, where it was 3,020 μg/g for GS and 2,911 μg/g for AAE, with lower but statistically insignificant difference. On the other hand, higher concentrations were obtained for the Zupljanka cultivar using AAE solvent (15,587 μg/g) compared with GS (10,197 μg/g). These values were statistically significant. Radovanović et al.( 2019), who used ultrasonic extraction (1 h, 40 mL of solvent con- sisting of methanol:acetone:water:acetic acid in a ratio of 30:42:27.5:0.5), discovered the concentration of 7,620 μg/g and 8,080 μg/g for the Merlot and Vranac varieties. Italian Journal of Food Science, 2023; 35 (3) 27 Content of selected polyphenolic substances in parts of grapevine Table 2. Comparison of concentrations of selected analytes in grapevine peel according to studies. Analyte Concentration (µg/g or % w/w**) Analytical method Concentration in Studies Resveratrol 6–255 HPLC/DAD Dry weight Iacopini et al. (2008) 4,700–8,400 HPLC/UV-VIS Residue Silva et al. (2018) 9.7 HPLC/PDA Fresh weight Ni et al. (2017) 21.5–174 HPLC/DAD Dry weight Chafer et al. (2005) 9.2–29.8 HPLC/PDA Dry weight Farhadi et al. (2016) 5.64–13.42 UHPLC/DAD/MSMS Frozen sample Pantelić et al. (2016) Rutin 403–1,690 HPLC/DAD Dry weight Iacopini et al. (2008) 140–150 HPLC/DAD Dry weight adovanović et al. (2019) 9,800–27,000 HPLC/UV-VIS Residue Silva et al. (2018) 15.1–54.4 HPLC/DAD Dry weight Chafer et al. (2005) 208–298 HPLC/PDA Dry weight Farhadi et al. (2016) 0.88–38.97 UHPLC/DAD/MSMS Frozen sample Pantelić et al. (2016) Quercetin 2.9–10.07 HPLC/DAD Dry weight Iacopini et al. (2008) 40–50 HPLC/DAD Dry weight Radovanović et al. (2019) 72.1–254.7 HPLC/DAD Dry weight Chafer et al. (2005) 306–405 HPLC/PDA Dry weight Farhadi et al. (2016) 0.57–121.94 UHPLC/DAD/MSMS Frozen sample Pantelić et al. (2016) Gallic acid 600–800 HPLC/UV-VIS Residue Silva et al. (2018) 1,360–1,400 HPLC/DAD Dry weight Radovanović et al. (2019) 70 HPLC/UV-VIS Extract Esparza et al. (2020) 8–38 HPLC/DAD Dry weight Jiménez-Moreno et al. (2019) 2–21 HPLC/MS/MS Dry weight Anastasiadi et al. (2012) 13–108 HPLC/DAD Extract Esparza et al. (2020) 120–140 HPLC/DAD Dry weight Radovanović et al. (2019) 0.041–0.215* HPLC/DAD Extract Prusova et al. (2020) Gallic acid >150 HPLC/UV-VIS Extract Esparza et al. (2020) 43–310 HPLC/DAD Dry weight Jiménez-Moreno et al. (2019) 70–469 HPLC/MS/MS Dry weight Anastasiadi et al. (2012) 10,500–11,500 HPLC/UV-VIS Residue Silva et al. (2018) 32,960 HPLC/DAD Dry extract Apostolou et al. (2013) 1,430–1,580 HPLC/DAD Dry weight Radovanović et al. (2019) 120–1,290 HPLC/DAD Extract Esparza et al. (2020) 0.822–4.015 HPLC/DAD Extract Prusova et al. (2020) Catechin 225–710 HPLC/DAD Dry weight Jiménez-Moreno et al. (2019) 385–1,858 HPLC/MS/MS Dry weight Anastasiadi et al. (2012) 900–3,500 HPLC/DAD Extract Esparza et al. (2020) 29,300–38,700 HPLC/UV-VIS Residue Silva et al. (2018) 157.57–1201.00 HPLC/MS-QTOF Dry weight Boso et al. (2019) 2,310–2,550 HPLC-DAD Dry weight Radovanović et al. (2019) 18.398–78.930* HPLC/DAD Extract Prusova et al. (2020) Epicatechin gallate 12.3–189 HPLC/MS/MS Dry weight Anastasiadi et al. (2012) 1.742–33.589* HPLC/DAD Extract Prusova et al. (2020) 7.04 HPLC/MS-QTOF Dry weight Boso et al. (2019) 2,460–2,600 HPLC/DAD Dry weight Radovanović et al. (2019) 15,500 HPLC/UV-VIS Of residue Silva et al. (2018) Resveratrol 10–370 HPLC/DAD Extract Esparza et al. (2020) 74–266 HPLC/MS/MS Dry weight Anastasiadi et al. (2012) >250 HPLC/UV-VIS Extract Esparza et al. (2020) 21–162 HPLC/DAD Dry weight Jiménez-Moreno et al. (2019) 2,150–25,410 HPLC/UV-VIS Dried extract Sahpazidou et al. (2014) Quercetin-3-glucoside 240–1,500 HPLC/DAD Extract Esparza et al. (2021) 54.1–137 HPLC/MS/MS Dry weight Anastasiadi et al. (2012) >800 HPLC/UV-VIS Extract Esparza et al. (2020) 96–485 HPLC/DAD Dry weight Jiménez-Moreno et al. (2019) 1.783–11.158* HPLC/DAD Extract Prusova et al. (2020) E-viniferin 150–690 HPLC/DAD Extract Esparza et al. (2021) >500 HPLC/UV-VIS Extract Esparza et al. (2020) 91–310 HPLC/DAD Dry weight Jiménez-Moreno et al. (2019) 167–499 HPLC/MS/MS Dry weight Anastasiadi et al. (2012) 170–760 HPLC/DAD Dry weight Leal et al. (2020) HPLC: high-performance liquid chromatography; UHPLC: ultra high-performance liquid chromatography; DAD: diode-array detection; PDA: photodiode array; QMS: quadrupole mass spectrometry; MS: mass spec-trometry; QTOF: quadrupole time of flight; FD: fluorescence detection. 36 Italian Journal of Food Science, 2023; 35 (3) Jurasova L et al. trans-caftaric acid as the phenol with highest concentra- tion in both white and red varieties (Anastasiadi et  al., 2012; Apostolou et al., 2013). The analysis of flavanols in the stems of red variet- ies showed the presence of diverse flavonols, with a high abundance of quercetin derivatives and the high- est content of quercetin-3-O-glucuronide (Negro et al., 2003; Souquet et al., 2000). In addition, quercetin-3-O- glucoside, quercetin-3-O-galactoside and quercetin- 3-O-rutinoside were the most abundantly discovered flavanols (Apostolou et al., 2013; Souquet et al., 2000). Comparison of red and white variety stems showed sim- ilar characterisation of flavanols, but with much higher flavanol content in red varieties. Catechin is the most abundant of all the flavan-3-ols, in both white and red varieties, with the highest concentra- tion in grape stems, followed by skins and seeds. Within white varieties, the analysis also showed that catechins are the most concentrated flavan-3-ols in all tissues, with the highest quantity found in grape stems. Analysis of stilbenes in grape residues from red variet- ies confirmed the presence of their derivatives in stems, seeds, pomaces and leaves. Contrarily, stilbenes have been found only in skins and stems in white varieties (Anastasiadi et al., 2012; Apostolou et al., 2013; Di Lecce et al., 2014; Rockenbach et al., 2011). Nowadays, grape stems as a winemaking by-product often represent undervalued material and a waste, a problem for the environment. The rich content of bioac- tive compounds potentiates grape stems as a prospective material for the introduction of added-value products. Grape stems are widely used for the production of alco- holic beverages, dietary fibre, plant protein supplements, animal feed and fertilisers (Arvanitoyannis et al., 2006), but bioactive compositions remain poorly defined. The transformation of agro-food wastes into products with added value has caught the attention of the food and pharmaceutical sectors (Martins et al., 2011). Owing to the presence of proanthocyanidins, grape stems and grape clusters are a source of compounds causing exces- sive astringent taste and influencing organoleptic prop- erties of wine. Therefore, they are removed before the vinification process, but the usage of this waste is being discussed intensively. The usage of grape waste as a material source for food production could lead to a replacement of intake of syn- thetic antioxidants with adverse effects. However, bioac- tive compounds contained in the vine and their impact on the human and animal health has to be investigated in detail. The chemical composition of grape stems, along with grape variety and growing conditions, strongly influence extraction processes. Domínguez-Perles et al. (2014) compared the conditions to increase the effectiveness of phenol extraction as determined by response surface methodology. Performing experiments on grape stems of Greek varieties, lower extraction temperature led to a 34% increase in extracted phenols. Compared with pomace and the whole bunch, ABTS showed significantly higher (p < 0.01) antioxidant activ- ity in grape stems. On the other hand, in Slovak samples, DPPH assay did not show significant differences in the antioxidant activities of grape by-products. In Slovakia and Austria, grape stems had significantly fewer (p < 0.01) proteins in comparison with grape pom- ace and bunch. Compared with grape pomace and bunch, TPC analysis showed significantly (p < 0.01) higher con- tent of grape stem in the samples of both countries. The comparison of Slovak and Austrian wine by-products was characterised by similar nutrition content, con- densed tannins and TPC as well as antioxidant activity. Gouvinhas et al. (2020) described the effect of climate and altitude on the production of phenols in grape stems. The authors discovered increased numbers of phenols, orthodiphenols and flavonoids in the grape stems cul- tivated in low altitude areas (Lower Corgo sub-region). This region is characterised by stressful vine conditions and represented by heavy rains caused by the Atlantic Ocean and thermal stress. Plants respond to stress by synthesising secondary metabolites, including phenols. The impact of thermal stress on these metabolites in the vine was evident during the 2017 and 2018 seasons. The results demonstrated that altitude was a determining fac- tor for the content of polyphenolics. Though fluctuating levels of phenols in stems were observed, this by-product is a potential source of phe- nols. Moreover, as in grape seed extracts, antimicrobial activity was observed in grape stem extracts against gastrointestinal tract bacteria S. aureus and E. faecalis. Additionally, Anastasiadi et al. (2012) described the anti- microbial activity of grape extracts caused by the high abundance of flavonoids, phenolic acids and stilbenes in stems along with flavonoids and their derivatives in seeds. This graph visually shows the least heterogeneous results in terms of percentage values. The rationale could be that the amount of phenolic compounds in the trefoil is least burdened by grapevine species. However, as mentioned above, the Folin method is highly burdened by interfer- ence, so we cannot prove this claim. Moreover, there are still noticeable differences over 100 mg/g. Italian Journal of Food Science, 2023; 35 (3) 37 Content of selected polyphenolic substances in parts of grapevine Catechin concentration was measured by Anastasiadi et al. (2012; 385–1,858 µg/g), Karvela et al. (2009; 900– 3,500 µg/g), Radovanović (2019; 2,310–2,550 µg/g) and Boso et al. (2019; 1,201 µg/g). The extraction method and solvent used differed depending on the study. For exam- ple, a mixture of methanol, water and some organic acid was applied, or a mixture of ethanol and water. Boso et al. (2019) used a two-step extraction method, but their results were still comparable with others (1,201 µg/g of catechin in stems from red variety). However, Boso et al. (2019) had measured a concentration of 157.57 µg/g dw in the stems of the white variety. Close to this value were the results of Jiménez-Moreno et al. (2019), who used different ethanol concentrations for extraction and found results in the range from 225–710 µg/g dw. Considering these results, we concluded that the extraction method was not a strong factor in the comparison of results. The lowest concentration was found by Prusova et al. (2020) in fresh weight. Epicatechin gallate The highest concentration of epicatechin gallate was determined by Silva et al. (2018; 15.5 mg/g), possibly because of assessing extract residue. This was followed by an epicatechin gallate concentration of 2.6 mg/g by Radovanović et al. (2019); these authors used ultrasonic extraction with a solvent consisting of methanol, acetone, water and acetic acid. The respective concentration of epi- catechin gallate discovered by Boso et al. (2019), Prusova et al. (2020), and Anastasiadi et al. (2012) was 12.3–189 µg/g dw, 1.742–33.589 mg/L of extract and 7.04 µg/g dw. Resveratrol Anastasiadi et al. (2012) and Jiménez-Moreno et al. (2019) reported the concentration of resveratrol as 74–266 µg/g and 21–162 µg/g dw, respectively. Jiménez- Moreno et al. (2019) investigated the influence of three process parameters on extraction: ethanol concentration, extraction temperature and solid/solvent ratio, observing a wide variety of results of all analytes. The most effec- tive extraction used 50% ethanol as solvent, a tempera- ture of 40°C and a 1:50 solid/solvent ratio. Esparza et al. (2020, 2021) analysed the concentration of resveratrol directly from grape stem extract with comparable results. Comparing the Assyrtiko, Mavrotragano, Voidomato and Muscat varieties, Sahpazidou et al. (2014) reported the lowest concentration in the white variety Assyrtiko (2,150 µg/g of extract), and the highest abundance in the red variety Voidomato (25,410 µg/g of extract). E-viniferin In contrast with other analytes, the value of Ε-viniferin was found to be the same throughout different studies (Esparza et al., 2020, 2021; Jiménez-Moreno et al., 2019). Analysing dry weight, the abundance of Ε-viniferin was in the range of 91 µg/g dw of stem powder of the Mazuleo The most abundant polyphenols in grape stems and their effect on health Gallic acid The highest amount of GA in grape stems was reported by Apostolou et al. (2013), that is, 32,960 µg/g of dry extract. The Mazuelo variety was studied by Jiménez- Moreno et al. (2019), whose results were in the range of 43–310 µg/g dw. They used solvent extraction with five levels of ethanol concentration, two ratios of solid and solvent, and two levels of extraction temperature. This could be the reason for the high scatter of results. GA in Mazuelo stem extracts was also studied by Esparza et al. (2020). The authors showed the result of a measured concentration higher than 150 µg/mg, which matched their results of 120–1,290 µg/g of extract from differ- ent Spanish varieties, including Mazuelo (Esparza et al., 2020). Ordinarily, the same results were measured in Mandilaria, Mavrotragano, Voidomatis, Asyrtiko, Athiri and Aidani in the range 70–469 µg/g dw. Quite higher results were discovered by Radovanović et al. (2019) using extraction with MeOH/H2O/HCl (1,430–1,580 µg/g dw) and Anastasiadi et al. (2012) (10.5–11.5 mg/g of residue). The lowest concentration of 0.822–4.005 µg/mL of extract was measured by Prusova et al. (2020). The rea- son for different results could be the extraction method. Moreover, Prusova et al (2020) worked with fresh mate- rial. As mentioned above, stems contain up to 80% water. Low concentration of GA in the range of 0.013–0.024 µg/g dw in grape stems was discovered by Teixeira et al. (2018). Esparza et al. (2020) reported a quercetin concentra- tion of >0.07 µg/mL of extract from dried powdered stems, and observed the impact of light and tempera- ture on the stability of phenolic compounds during stor- age. Prusova et al. (2020) measured a concentration of 0.041–0.215 µg/mL of quercetin extract from fresh stems of 10–12-year-old vines. Relatively small concentrations were due to its calculation of analyte in diluted stem extract. Contrarily, Radovanović et al. (2019) Anastasiadi et al. (2012) and Jiménez-Moreno et al. (2019) reported quercetin concentrations of 8–38 µg/g, 2–21 µg/g and 120–140 µg/g of dw, respectively, and the highest con- centrations were observed in the Merlot and Vranac varieties. Vines were cultured in Serbia, and dried, milled, and phenols were extracted using ultrasound-as- sisted extraction with a mixture of methanol:acetone: water:acetic acid (ratio: 30:42:27.5:0.5) (Radovanović et al., 2019). Catechin The highest catechin concentration was measured by Silva et al. (2018) in dry extract residue (29.3–38.7 mg/g). 38 Italian Journal of Food Science, 2023; 35 (3) Jurasova L et al. determine the most studied analytes. We observed vari- ations in the determination of total polyphenolic com- pounds in Figures 1–4. These variations could be due to the use of different solvents or the strong influence of interferences, such as carbohydrates, in the method used. However, it is clear that the higher proportion of pheno- lic compounds is found in seeds and stems, compared with lower proportions in the fruit peel. In general, the pulp of the berry contains the least proportion of pheno- lic compounds. Funding This paper was supported by the project “Study of polyphenolics compounds in wines and parts vines” IGA-ZF/2021-SI2009, and by CZ.02.1.01/0.0/0.0/ l6_0l7/0002334 Research Infrastructure for Young Scientists, co-financed by Operational Programme Research, Development and Education. References Abarghuei, M.J., Rouzbehan, Y. and Alipour, D. 2010. The influence of the grape pomace on the ruminal parameters of sheep. 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Conclusion Phenolic compounds are secondary metabolites of plants; accordingly, these are not necessary for plant growth and development but are essential for plant survival. Phenolic compounds play an important role in photo- synthesis, respiration, and plant defence, among others. In recent years, interest in the detailed study of phenolic compounds has increased, mainly because of their pos- itive effects on human health. Their presence in grapes has already been proved by many studies. However, the reported concentrations of total and individual poly- phenols vary widely. It depends on the way the sample is treated, the method used, the detector used, and the calculation to dry or fresh matter. By comparing the determined values of selected ana- lytes from different parts of grapevine, a large variabil- ity in individual results of different studies was observed. Therefore, it was concluded that the concentration deter- mined not only depended on the choice of variety and the site of growing habitat of the plant but also on the choice of extraction conditions, analytical methods and labo- ratory conditions. The most commonly used technique is the extraction method with mixtures of organic sol- vents and water. The mixtures used are adjusted accord- ing to the desired polarity. The most common analytical method used is HPLC, or its variations with mass and spectrophotometric detectors or combinations thereof. We were not able to determine the phenolic substance that was concentrated in each part of the plant, because individual studies provided these concentrations based on their measurements. 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