Sweet cherry pomace is an important source of phenolic compounds with beneficial health properties. As after the extraction of phenolic compounds, a phenolic fraction called nonextractable polyphenols (NEPs) remains usually retained in the extraction residue, alkaline and acid hydrolyses and enzymatic-assisted extraction (EAE) were carried out in this work to recover NEPs from the residue of conventional extraction from sweet cherry pomace. In vitro and in vivo evaluation of the antioxidant, antihypertensive, antiaging, and neuroprotective capacities employing Caenorhabditis elegans was achieved for the first time. Extractable phenolic compounds and NEPs were separated and identified by families by high-performance thin-layer chromatography (HPTLC) with UV/Vis detection. A total of 39 phenolic compounds were tentatively identified in all extracts by direct analysis in real-time high-resolution mass spectrometry (DART-Orbitrap-HRMS). EAE extracts presented the highest in vitro and in vivo antioxidant capacity as well as the highest in vivo antiaging and neuroprotective capacities. These results showed that NEPs with interesting biological properties are retained in the extraction residue, being usually underestimated and discarded.

Archer Daniels Midland Nutrition Health and Wellness Biopolis S L Parc Scientific Universitat de València C Catedrático Agustín Escardino Benlloch 9 Paterna 46980 Valencia Spain

Mendel University in Brno Department of Chemistry and Biochemistry Zemedelska 1 CZ 613 00 Brno Czech Republic

Universidad de Alcalá Departamento de Química Analítica Química Física e Ingeniería Química Facultad de Ciencias Ctra Madrid Barcelona Km 33 600 28871 Alcalá de Henares Madrid Spain

Universidad de Alcalá Instituto de Investigación Química Andrés M del Río Ctra Madrid Barcelona Km 33 600 28871 Alcalá de Henares Madrid Spain

Zobrazit více v PubMed

Indo H. P.; Yen H. C.; Nakanishi I.; Matsumoto K.; Tamura M.; Nagano Y.; Matsui H.; Gusev O.; Cornette R.; Okuda T.; Minamiyama Y.; Ichikawa H.; Suenaga S.; Oki M.; Sato T.; Ozawa T.; Clair D. K.; Majima H. J. A mitochondrial superoxide theory for oxidative stress diseases and aging. J. Clin. Biochem. Nutr 2015, 56, 1–7. 10.3164/jcbn.14-42. PubMed DOI PMC

González-Jiménez F. E.; Hernández-Espinosa N.; Cooper-Bribiesca B. L.; Núñez-Bretón L. C.; Reyes-Reyes M. Empleo de antioxidantes en el tratamineto de diversaas enfermedades crónico-degenerativas. Vertientes 2015, 18, 16–21.

Hamaguchi T.; Ono K.; Murase A.; Yamada M. Phenolic compounds prevent Alzheimer′s pathology through different effects on the amyloid-β aggregation pathway. Am. J. Clin. Pathol 2009, 175, 2557–2565. 10.2353/ajpath.2009.090417. PubMed DOI PMC

Ono K.; Li L.; Takamura Y.; Yoshiike Y.; Zhu L.; Han G.; Mao X.; Ikeda T.; Takasaki J.; Nishijo H.; Takashima A.; Teplow D. B.; Zagorski M. G.; Yamada M. Phenolic compounds prevent-amyloid β-protein oligomerization and synapic dysfunction by site-specific binding. J. Biol. Chem. 2012, 287, 14631–14643. 10.1074/jbc.M111.325456. PubMed DOI PMC

Tuppo E. E.; Arias H. R. The role of inflammation in Alzheimer′s disease. Int. J. Biochem 2005, 37, 289–305. 10.1016/j.biocel.2004.07.009. PubMed DOI

Ozben T.; Ozben S. Neuro-inflammation and anti-inflammatory treatment options for Alzheimer’s disease. Clin. Biochem 2019, 72, 87–89. 10.1016/j.clinbiochem.2019.04.001. PubMed DOI

Yasar S.; Xia J.; Yao W.; Furberg C. D.; Xue Q. L.; Mercado C. I.; Fitzpatrick A. L.; Fried L. P.; Kawas C. H.; Sink K. M.; Williamson J. D.; Dekosky S. T.; Carlson M. C. Antihypertensive drugs decrease risk of Alzheimer disease. Neurology 2013, 81, 896–903. 10.1212/WNL.0b013e3182a35228. PubMed DOI PMC

Kennelly S. P.; Lawlor B. A.; Kenny R. A. Blood pressure and dementia. A comprehensive review. Ther. Adv. Neurol. Disord. 2009, 2, 241–260. 10.1177/1756285609103483. PubMed DOI PMC

Kim J.; Lee H. J.; Lee K. W. Naturally occurring phytochemicals for the prevention of Alzheimer’s disease. J. Neurochem 2010, 112, 1415–1430. 10.1111/j.1471-4159.2009.06562.x. PubMed DOI

Landete J. M. Dietary intake of natural antioxidants: Vitamins and polyphenols. Crit. Rev. Food Sci. Nutr. 2013, 53, 706–721. 10.1080/10408398.2011.555018. PubMed DOI

Figueiredo E. A. d.; Alves N. F. B.; Monteiro M. M. d. O.; Cavalcanti C. d. O.; Silva T. M. S. d.; Silva T. M. G. d.; Braga V. d. A.; Oliveira E. d. J. Antioxidant and antihypertensive effects of a chemically defined fraction of Syrah red wine on spontaneously hypertensive rats. Nutrients 2017, 9, 574.10.3390/nu9060574. PubMed DOI PMC

Martini S.; Conte A.; Tagliazucchi D. Phenolic compounds profile and antioxidant properties of six sweet cherry (Prunus avium) cultivars. Food Res. Int. 2017, 97, 15–26. 10.1016/j.foodres.2017.03.030. PubMed DOI

Gonçalves A. C.; Bento C.; Jesus F.; Alves G.; Silva L. R. Chapter 2 - Sweet cherry phenolic compounds: Identification, characterization, and health benefits, studies in natural products chemistry. Studies in Natural Product Chemisty 2018, 59, 31–78. 10.1016/B978-0-444-64179-3.00002-5. DOI

Ono K.; Condron M. M.; Teplow D. B. Structure-neurotoxicity relationships of amyloid β-protein oligomers. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 14745–14750. 10.1073/pnas.0905127106. PubMed DOI PMC

Roychaudhuri R.; Yang M.; Hoshi M. M.; Teplow D. B. Amyloid β protein assembly and Alzheimer disease. J. Biol. Chem. 2009, 284, 4749–4753. 10.1074/jbc.R800036200. PubMed DOI PMC

Grassi D.; Desideri G.; Necozione S.; Lippi C.; Casale R.; Properzi G.; Blumberg J. B.; Ferri C. Blood pressure is reduced and inssulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J. Nutr. 2008, 138, 1671–1676. 10.1093/jn/138.9.1671. PubMed DOI

Woźniak L.; Marszałek K.; Skąpska S. Extraction of phenolic compounds from sour cherry pomace with supercritical carbon dioxide: Impact of process parameters on the composition and antioxidant properties of extracts. Sep. Sci. Technol. 2016, 51, 1472–1479. 10.1080/01496395.2016.1165705. DOI

Aguilar-Méndez M. A.; Campos-Arias M. P.; Quiroz-Reyes C.; Ronquillo-de Jesús E.; Cruz-Hernández M. A. Fruit peels as sources of bioactive compounds with antioxidant and antimicrobial properties. Revista FCA UNCUYO 2019, 1853–8665.

Bujdosó G.; Hrotko K. Cherry production. Cherries: Botany, Production and Uses 2017, 1–13. 10.1079/9781780648378.0001. DOI

Górnas P.; Rudzinska M.; Raczyk M.; Misina I.; Seglina D. Impact of cultivar on profile and concentration of lipophilic bioactive compounds in kernel oils recovered from sweet cherry (Prunus avium L.) by-products. Plant Foods Hum. Nutr 2016, 71, 158–164. 10.1007/s11130-016-0538-5. PubMed DOI

Dominguez-Rodriguez G.; Marina M. L.; Plaza M. Enzyme-assisted extraction of bioactive non-extractable polyphenols from sweet cherry (Prunus avium L.) pomace. Food Chem. 2021, 339, 128086.10.1016/j.foodchem.2020.128086. PubMed DOI

McCune L. M.; Kubota C.; Stendell-Hollis N. R.; Thomson C. A. Cherries and health: a review. Crit. Rev. Food Sci. Nutr 2010, 51, 1–12. 10.1080/10408390903001719. PubMed DOI

Acero N.; Gradillas A.; Beltran M.; García A.; Muñoz Mingarro D. Comparison of phenolic compounds profile and antioxidant properties of different sweet cherry (Prunus avium L.) varieties. Food Chem. 2019, 279, 260–271. 10.1016/j.foodchem.2018.12.008. PubMed DOI

Pataro G.; Carullo D.; Bobinaite R.; Donsi G.; Ferrari G. Improving the extraction yield of juice and bioactive compounds from sweet cherries and their by-products by pulsed electric fields. Chem. Eng. Trans 2017, 57, 1717–1722. 10.3303/CET1757287. DOI

Dominguez-Rodriguez G.; Marina M. L.; Plaza M. Strategies for the extraction and analysis of non-extractable polyphenols from plants. J. Chromatogr. A 2017, 1514, 1–15. 10.1016/j.chroma.2017.07.066. PubMed DOI

Pérez-Jiménez J.; Díaz-Rubio M. E.; Saura-Calixto F. Non-extractable polyphenols, a major dietary antioxidant: occurrence, metabolic fate and health effects. Nutr. Res. Rev. 2013, 26, 118–129. 10.1017/S0954422413000097. PubMed DOI

Cheng A.; Yan H.; Han C.; Chen X.; Wang W.; Xie C.; Qu J.; Gong Z.; Shi X. Acid and alkaline hydrolysis extraction of non-extractable polyphenols in blueberries: Optimisation by response surface methodology. Czech J. Food Sci. 2014, 32, 218–225. 10.17221/257/2013-CJFS. DOI

Gennette M.Extractable and non-extractable polyphenols from apples: potential anti-inflammatory agents. Master Thesis, University of Massachusetts, Amherst, 2017.

Pérez-Jiménez J.; Arranz S.; Saura-Calixto F. Proanthocyanidin content in foods is largely underestimated in the literature data: an approach to quantification of the missing proanthocyanidins. Food Res. Int. 2009, 42, 1381–1388. 10.1016/j.foodres.2009.07.002. DOI

Fernández K.; Vega M.; Aspé E. An enzymatic extraction of proanthocyanidins from País grape seeds and skins. Food Chem. 2015, 168, 7–13. 10.1016/j.foodchem.2014.07.021. PubMed DOI

Nemes A.; Szőllősi E.; Stündl L.; Biró A.; Homoki J. R.; Szarvas M. M.; Balogh P.; Cziáky Z.; Remenyik J. Determination of flavonoid and proanthocyanidin profile of hungarian sour cherry. Molecules 2018, 23, 3278.10.3390/molecules23123278. PubMed DOI PMC

Pérez-Jiménez J.; Torres J. L. Analysis of nonextractable phenolic compounds in foods: The current state of the art. J. Agric. Food Chem. 2011, 59, 12713–12724. 10.1021/jf203372w. PubMed DOI

Li L.; Sun B. Grape and wine polymeric polyphenols: Their importance in enology. Crit. Rev. Food Sci. Nutr 2019, 59, 563.10.1080/10408398.2017.1381071. PubMed DOI

Suo H.; Tian R.; Li J.; Zhang S.; Cui Y.; Li L.; Sun B. Compositional characterization study on high molecular mass polymeric polyphenols in red wines by chemical degradation. Food Res. Int. 2019, 123, 440–449. 10.1016/j.foodres.2019.04.056. PubMed DOI

Pérez-Ramírez I. F.; Reynoso-Camacho R.; Saura-Calixto F.; Pérez-Jiménez J. Comprehensive characterization of extractable and non-extractable phenolic compounds by high-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight of a grape/pomegranate pomace dietary supplement. J. Agric. Food Chem. 2018, 66, 661–673. 10.1021/acs.jafc.7b05901. PubMed DOI

Stanek N.; Jasicka-Misiak I. HPTLC phenolic profiles as useful tools for the authentication of honey. Food Anal. Methods 2018, 11, 2979–2989. 10.1007/s12161-018-1281-3. DOI

Eren Y.; Ozata A. Determination of mutagenic and cytotoxic effects of Limonium globuliferum aqueous extracts by Allium, Ames, and MTT test. Rev. Bras. Farmacogn 2014, 24, 51–59. 10.1590/0102-695X20142413322. DOI

Yue Y.; Li S.; Shen P.; Park Y. Caenorhabditis elegans as a model for obesity research. Curr. Res. Food Sci. 2021, 4, 692–97. 10.1016/j.crfs.2021.09.008. PubMed DOI PMC

Shen Y.; Wen Q.; Liu H.; Zhong C.; Qin Y.; Harris G.; Kawano T.; Wu M.; Xu T.; Samuel A. D.; Zhang Y. An extrasynaptic GABAergic signal modulates a pattern of forward movement in Caenorhabditis elegans. Elife 2016, 5, 14197.10.7554/eLife.14197. PubMed DOI PMC

Iriondo-DeHond A.; Martorell P.; Genovés S.; Ramón D.; Stamatakis K.; Fresno M.; Molina A.; Del Castillo M. D. Coffee silverskin extract protects against accelerated aging caused by oxidative agents. Molecules 2016, 21, 721.10.3390/molecules21060721. PubMed DOI PMC

van de Klashorst D.; van den Elzen A.; Weeteling J.; Roberts M.; Desai T.; Bottoms L.; Hughes S. Montmorency tart cherry (Prunus cerasus L.) acts as a calorie restriction mimetic that increases intestinal fat and lifespan in Caenorhabditis elegans. J. Funct. Foods 2020, 68, 103890.10.1016/j.jff.2020.103890. DOI

Hartzfeld P. W.; Forkner R.; Hunter M. D.; Hagerman A. E. Determination of hydrolyzable tannins (gallotannins and ellagitannins) after reaction with potassium iodate. J. Agric. Food Chem. 2002, 50, 1785–1790. 10.1021/jf0111155. PubMed DOI

Arranz S.; Saura-Calixto F. Analysis of polyphenols in cereals may be improved performing acidic hydrolysis: a study in wheat flour and wheat bran and cereals of the diet. J. Cereal Sci. 2010, 51, 313–318. 10.1016/j.jcs.2010.01.006. DOI

Kosar M.; Dorman H. J. D.; Hiltunen R. Effect of an acid treatment on the phytochemical and antioxidant characteristics of extracts from selected Lamiaceae species. Food Chem. 2005, 91, 525–533. 10.1016/j.foodchem.2004.06.029. DOI

Montero L.; Herrero M.; Ibáñez E.; Cifuentes A. Profiling of phenolic compounds from different apple varieties using comprehensive two-dimensional liquid chromatography. J. Chromatogr. A 2013, 1313, 275–283. 10.1016/j.chroma.2013.06.015. PubMed DOI

Gu H. F.; Li C. M.; Xu Y.; Hu W.; Chen M.; Wan Q. Structural features and antioxidant activity of tannin from persimmon pulp. Food Res. Int. 2008, 41, 208–217. 10.1016/j.foodres.2007.11.011. DOI

Dominguez-Rodriguez G.; Plaza M.; Marina M. L. High-performance thin-layer chromatography and direct analysis in real time-high resolution mass spectrometry of non-extractable polyphenols from tropical fruit peels. Food Res. Int. 2021, 147, 110455.10.1016/j.foodres.2021.110455. PubMed DOI

Falk M.; Falková I.; Kopecná O.; Baciková A.; Pagácová E.; Simek D.; Golan M.; Kozubek S.; Pekarová M.; Follett S. E.; Klejdus B.; Elliott K. W.; Varga K.; Teplá O.; Kratochvílová I. Chromatin architecture changes and DNA replication fork collapse are critical features in cryopreserved cells that are differentially controlled by cryoprotectans. Sci. Rep 2018, 8, 14694.10.1038/s41598-018-32939-5. PubMed DOI PMC

Brand-Williams W.; Cuvelier M. E.; Berset C. Use of a free radical method to evaluate antioxidant activity. LWT- Food Sci. Technol. 1995, 28, 25–30. 10.1016/S0023-6438(95)80008-5. DOI

Re R.; Pellegrini N.; Proteggente A.; Pannala A.; Yang M.; Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med. 1999, 26, 1231.10.1016/S0891-5849(98)00315-3. PubMed DOI

Geng F.; He Y.; Yang L.; Wang Z. A rapid assay for angiotensin-converting enzyme activity using ultra-performance liquid chromatography–mass spectrometry. Biomed. Chromatogr 2010, 24, 312–317. 10.1002/bmc.1291. PubMed DOI

Azmi N.; Hashim P.; Hashim D. M.; Halimoon N.; Majid N. M. N. Anti-elastase, anti-tyrosinase and matrix metalloproteinase-1 inhibitory activity of earthworm extracts as potential new anti-aging agent. Asian Pac J. Trop Biomed 2014, 4, S348–352. 10.12980/APJTB.4.2014C1166. PubMed DOI PMC

Mathew M.; Subramanian S. In vitro screening for anti-cholinesterase and antioxidant activity of methanolic extracts of ayurvedic medicinal plants used for cognitive disorders. PLoS One 2014, 9, e86804.10.1371/journal.pone.0086804. PubMed DOI PMC

Martorell P.; Forment J. V.; de Llanos R.; Montón F.; Llopis S.; González N.; Genovés S.; Cienfuegos E.; Monzó H.; Ramón D. Use of Saccharomyces cerevisiae and Caenorhabditis elegans as model organisms to study the effect of cocoa polyphenols in the resistance to oxidative stress. J. Agric. Food Chem. 2011, 59, 2077–85. 10.1021/jf104217g. PubMed DOI

Link C. D. Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans. Proc. Natl. Acad. Sci. 1995, 92, 9368–9372. 10.1073/pnas.92.20.9368. PubMed DOI PMC

Hernández-Corroto E.; Marina M. L.; García M. C. Multiple protective effect of peptides released from Olea europaea and Prunus persica seeds against oxidative damage and cancer cell proliferation. Food Res. Int. 2018, 106, 458–467. 10.1016/j.foodres.2018.01.015. PubMed DOI

Su D.; Zhang R.; Hou F.; Zhang M.; Guo J.; Huang F.; Deng Y.; Wei Z. Comparison of the free and bound phenolic profiles and cellular antioxidant activities of litchi pulp extracts from different solvents. BMC Complement Altern Med. 2014, 14, 9.10.1186/1472-6882-14-9. PubMed DOI PMC

Gardana C.; Simonetti P. Evaluation of the degree of polymerization of the proanthocyanidins in cranberry by molecular sieving and characterization of the low molecular weight fractions by UHPLC-Orbitrap mass spectrometry. Molecules 2019, 24, 1504.10.3390/molecules24081504. PubMed DOI PMC

Waterman P. G.; Mole S.. Analysis of phenolic plant metabolites; Methods in Ecology; Blackwell Scientific: Oxford, 1994; pp 151–154.

Iglesias-Carres L.; Mas-Capdevila A.; Bravo F. I.; Mulero M.; Muguerza B.; Arola-Arnal A. Optimization and characterization of Royal Dawn cherry (Prunus avium) phenolics extraction. Sci. Rep 2019, 9, 17626.10.1038/s41598-019-54134-w. PubMed DOI PMC

Yılmaz F. M.; Karaaslan M.; Vardin H. Optimization of extraction parameters on the isolation of phenolic compounds from sour cherry (Prunus cerasus L.) pomace. J. Food Sci. Technol. 2015, 52, 2851–9. 10.1007/s13197-014-1345-3. PubMed DOI PMC

Martini S.; Conte A.; Tagliazucchi D. D, Phenolic compounds profile and antioxidant properties of six sweet cherry (Prunus avium) cultivars. Food Res. Int. 2017, 97, 15–26. 10.1016/j.foodres.2017.03.030. PubMed DOI

Di Matteo A.; Russo R.; Graziani G.; Ritieni A.; Di Vaio C. Characterization of autochthonous sweet cherry cultivars (Prunus avium L.) of southern Italy for fruit quality, bioactive compounds and antioxidant activity. J. Sci. Food Agri 2017, 97, 2782–2794. 10.1002/jsfa.8106. PubMed DOI

Aires A.; Dias C.; Carvalho R.; Saavedra M. J. Analysis of glycosylated flavonoids extracted from sweet-cherry stems, as antibacterial agents against pathogenic Escherichia coli isolates. Acta Biochim. Pol 2017, 64, 265–271. 10.18388/abp.2016_1374. PubMed DOI

Hu T.; Subbiah V.; Wu H.; BK A.; Rauf A.; Alhumaydhi F. A.; Suleria H. A. R. Determination and characterization of phenolic compounds from Australia-Grown sweet cherries (Prunus avium L.) and their potential antioxidant properties. ACS Omega 2021, 6, 34687–34699. 10.1021/acsomega.1c05112. PubMed DOI PMC

Jesus F.; Gonçalves A. C.; Alves G.; Silva L. R. Exploring the phenolic profile, antioxidant, antidiabetic and anti-hemolytic potential of Prunus avium vegetal parts. Food Res. Int. 2019, 116, 600–610. 10.1016/j.foodres.2018.08.079. PubMed DOI

Bursal E.; Köksal E.; Gülçin I.; Bilsel G.; Gören A. C. Antioxidant activity and polyphenol content of cherry stem (Cerasus avium L.) determined by LC–MS/MS. Food Res. Int. 2013, 51, 66–74. 10.1016/j.foodres.2012.11.022. DOI

Gonçalves A. C.; Bento C.; Silva B.; Simões M.; Silva L. R. Nutrients, bioactive compounds and bioactivity: The health benefits of sweet cherries (Prunus avium L.). Curr. Nutr. Food Sci. 2018, 14, 208.10.2174/1573401313666170925154707. DOI

Nunes A. R.; Gonçalves A. C.; Alves G.; Falcão A.; García-Viguera C.; Moreno D. A.; Silva L. R. Valorisation of Prunus avium L. by-products: Phenolic composition and effect on Caco-2 cells viability. Foods 2021, 10, 1185.10.3390/foods10061185. PubMed DOI PMC

Hassan F. A.; Ismail A.; Abdulhamid A.; Azlan A. Identification and quantification of phenolic compounds in bambangan (Mangifera pajang Kort.) peels and their free radical scavenging activity. J. Agric. Food Chem. 2011, 59, 9102–9111. 10.1021/jf201270n. PubMed DOI

Dominguez-Rodriguez G.; García M. C.; Plaza M.; Marina M. L. Revalorization of Passiflora species peels as a sustainable source of antioxidant phenolic compounds. Sci. Total Environ. 2019, 696, 134030.10.1016/j.scitotenv.2019.134030. DOI

Boncler M.; Golanski J.; Lukasiak M.; Redzynia M.; Dastych J.; Watala C. A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis. PLoS One 2017, 12, e0180022.10.1371/journal.pone.0180022. PubMed DOI PMC

Kundishora A.; Sithole S.; Mukanganyama S. Determination of the cytotoxic effect of different leaf extracts from Parinari curatellifolia (Chrysobalanaceae). J. Toxicol 2020, 2020, 8831545.10.1155/2020/8831545. PubMed DOI PMC