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Bionanotechnological innovations to improve the bioavailability of flavonoid polyphenols: a review
The study is devoted to a comprehensive analysis of flavonoid polyphenolic compounds, which play an important role in the regulation of key biological processes in the organism. These compounds have numerous functions, including antioxidant, anti-inflammatory, immunomodulatory, and epigenetic effects. Due to their ability to interact with a variety of biomolecules, polyphenols are involved in the modulation of signaling, which helps to reduce oxidative stress and improve cellular homeostasis. However, their use is limited by low bioavailability caused by complex metabolic processes and insufficient stability during transportation and storage. The bionanotechnological approaches aimed at optimizing the delivery and efficacy of polyphenols are considered. Innovative nanoparticle-based systems that improve the stability and absorption of these compounds in body tissues have been analyzed. Flavonoid-modified nanoparticles provide targeted action and prolonged release of bioactive substances. The study focuses on the effect of polyphenols on the regulation of Nrf2, AMPK and mTOR signaling pathways responsible for adaptation to oxidative stress, metabolic balance and immune system support. Their role in modulating epigenetic processes, such as DNA methylation and histone modification, is also considered, which is important for the long-term regulation of genetic activity and adaptive responses of the body. The results of the study indicate a significant potential of nanotechnology using to increase the bioavailability of polyphenols. The development of nanoforms for the delivery of phytonutrients contributes to the creation of functional foods and medicines. The use of nanoparticles can also reduce side effects and increase the bioefficiency of active components.
Key words: polyphenols, antioxidant properties, anti-inflammatory properties, endothelial function, Nrf2 pathway, gut microbiota, absorption, metabolism, epigenetic changes, cyclooxygenase.
Reference:
1. Bitiutskyi, V.S., Tsekhmistrenko, I.S., Melnychenko, Yu.O., Tsekhmistrenko, S.I. (2023). Syhnalnyi shliakh Wnt, metabolizm Kaltsiiu i Fosforu ta rehuliuiucha rol flavonoidu kvertsetynu [Wnt signaling pathway, calcium and phosphorus metabolism and the regulatory role of the flavonoid quercetin]. Tekhnolohii, instrumenty ta stratehii realizatsii naukovykh doslidzhen [Technologies, tools and strategies for implementing scientific research]. Dnipro, pp. 97–100.
2. Tsekhmistrenko, S.I., Bitiutskyi, V.S., Tsekhmistrenko, O.S., Demchenko, O.A., Tymoshok, N.O., Melnychenko, O.M. (2022). Ekolohichni biotekhnolohii “zelenoho” syntezu nanochastynok metaliv, oksydiv metaliv, metaloidiv ta yikh vykorystannia: naukova monohrafiia [Environmental biotechnology of “green” synthesis of metal nanoparticles, metal oxides, metalloids and their use]. Bila Tserkva, 270 p.
3. Tsekhmistrenko, S.I., Bitiutskyi, V.S., Tsekhmistrenko, O.S. (2023). Fiziolohichna rol flavonoidiv ta yikh praktychne vykorystannia. Innovatsiini tekhnolohii v ahronomii, zemleustroi, elektroenerhetytsi, lisovomu ta sadovo-parkovomu hospodarstvi: materialy mizhnarodnoi naukovo-praktychnoi konferentsii [Physiological role of flavonoids and their practical use. Innovative technologies in agronomy, land management, power engineering, forestry and horticulture: materials of the international scientific and practical conference]. Bila Tserkva, pp. 67–69.
4. Ramirez-Sanchez, I., Taub, P.R., Ciaraldi, T.P., Nogueira, L., Coe, T., Perkins, G., Villarreal, F. (2013). (−)-Epicatechin rich cocoa mediated modulation of oxidative stress regulators in skeletal muscle of heart failure and type 2 diabetes patients. International journal of cardiology. Vol. 168(4), pp. 3982–3990. DOI: 10.1016/j.ijcard.2013.06.089
5. Morel, I., Lescoat, G., Cillard, P., Cillard, J. (1994). [43] Role of flavonoids and iron chelation in antioxidant action. In Methods in enzymology. Academic Press. Vol. 234, pp. 437–443. DOI: 10.1016/0076-6879(94)34114-1
6. Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Nabeshima, Y.I. (1997). An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochemical and biophysical research communications. Vol. 236(2), pp. 313–322. DOI: 10.1006/bbrc.1997.6943
7. Kay, C.D., Pereira-Caro, G., Ludwig, I.A., Clifford, M.N., Crozier, A. (2017). Anthocyanins and flavanones are more bioavailable than previously perceived: A review of recent evidence. Annual Review of Food Science and Technology. Vol. 8(1), pp. 155–180. DOI: 10.1146/annurev-food-030216-025636
8. Fan, W., Zong, H., Zhao, T., Deng, J., Yang, H. (2024). Bioactivities and mechanisms of dietary proanthocyanidins on blood pressure lowering: A critical review of in vivo and clinical studies. Critical Reviews in Food Science and Nutrition. Vol. 64(11), pp. 3522–3538. DOI: 10.1080/10408398.2022.2132375
9. Bityutskyy, V., Tsekhmistrenko, S., Demchenko, O., Tsekhmistrenko, O., Melnychenko, Yu., Kharchyshyn, V. (2023). Bionanotechnological strategies for the synthesis of quercetin conjugates with selenium nanoparticles for their targeting of the Wnt/Ca2+ signaling pathway. «Animal Husbandry Products Production and Processing». no. 2 (182), pp. 100–107. DOI: 10.33245/2310-9289-2023-182-2-100-107
10. Tsekhmistrenko, S., Bityutskyy, V., Tsekhmistrenko, O., Merzlo, S., Tymoshok, N., Melnichenko, A., Yakymenko, I. (2021). Bionanotechnologies: synthesis of metals’nanoparticles with using plants and their applications in the food industry: A review. The Journal of Microbiology, Biotechnology and Food Sciences. Vol. 10(6), e1513. DOI: 10.15414/ jmbfs.1513
11. Birringer, M. (2011). Hormetics: dietary triggers of an adaptive stress response. Pharmaceutical research. Vol. 28, pp. 2680–2694. DOI: 10.1007/ s11095-011-0551-1
12. Bors, W., Michel, C., Stettmaier, K. (2001). Structure-activity relationships governing antioxidant capacities of plant polyphenols. In Methods in enzymology. Academic Press. Vol. 335, pp. 166–180. DOI: 10.1016/S0076-6879(01)35241-2
13. Bowtell, J., Kelly, V. (2019). Fruit-derived polyphenol supplementation for athlete recovery and performance. Sports Medicine. Vol. 49 (Suppl 1), pp. 3–23. DOI: 10.1007/s40279-018-0998-x
14. Chakrabarti, S.K., Chattopadhyay, D. (2024). Expanding Role of Epigenetics in Human Health and Disease. Exploratory Research and Hypothesis in Medicine. Vol. 9(3), pp. 221–235. DOI: 10.14218/ERHM.2023.00086
15. Clifford, M.N. (2004). Diet-derived phenols in plasma and tissues and their implications for health. Planta medica. Vol. 70(12), pp. 1103–1114. DOI: 10.1055/s-2004-835835
16. Lonati, E., Carrozzini, T., Bruni, I., Mena, P., Botto, L., Cazzaniga, E., Bulbarelli, A. (2022). Coffee-derived phenolic compounds activate Nrf2 antioxidant pathway in I/R injury in vitro model: A nutritional approach preventing age related-damages. Molecules. Vol. 27(3), 1049 p. Available at: https:// www.mdpi.com/1420-3049/27/3/1049#
17. Crozier, A., Del Rio, D., Clifford, M.N. (2010). Bioavailability of dietary flavonoids and phenolic compounds. Molecular aspects of medicine. Vol. 31, no. 6, pp. 446–467. DOI: 10.1016/j. mam.2010.09.007
18. Yu, J., Peng, Y., Wu, L.C., Xie, Z., Deng, Y., Hughes, T., Liu, Z. (2013). Curcumin down-regulates DNA methyltransferase 1 and plays an anti-leukemic role in acute myeloid leukemia. PloS one. Vol. 8(2), e55934. DOI: 10.1371/journal.pone.0055934
19. Day, A.J., Cañada, F.J., Dı́ az, J.C., Kroon, P.A., Mclauchlan, R., Faulds, C.B., Williamson, G. (2000). Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS letters. Vol. 468(2–3), pp. 166–170. DOI: 10.1016/S0014-5793(00)01211-4
20. Russo, G.L., Vastolo, V., Ciccarelli, M., Albano, L., Macchia, P.E., Ungaro, P. (2017). Dietary polyphenols and chromatin remodeling. Critical reviews in food science and nutrition. Vol. 57(12), pp. 2589–2599. DOI: 10.1080/10408398.2015. 1062353
21. Rothwell, J.A., Medina, Remón, A., Pérez, Jiménez, J., Neveu, V., Knaze, V., Slimani, N., Scalbert, A. (2015). Effects of food processing on polyphenol contents: A systematic analysis using Phenol Explorer data. Molecular nutrition & food research. Vol. 59(1), pp. 160–170. DOI: 10.1002/mnfr.201400494
22. El-Hadary, A.A.R., Sulieman, A.M., ElShorbagy, G.A. (2022). Comparative the antioxidants characteristics of orange and potato peels extracts under differences in pressure and conventional extractions. pp. 159–174. DOI: 10.34302/crpjfst/2022.14.1.13
23. Niether, W., Smit, I., Armengot, L., Schneider, M., Gerold, G., Pawelzik, E. (2017). Environmental growing conditions in five production systems induce stress response and affect chemical composition of cocoa (Theobroma cacao L.) beans. Journal of agricultural and food chemistry. Vol. 65(47), pp. 10165–10173. DOI: 10.1021/acs.jafc.7b04490
24. Guillaumet-Adkins, A., Yañez, Y., PerisDiaz, M.D., Calabria, I., Palanca-Ballester, C., Sandoval, J. (2017). Epigenetics and oxidative stress in aging. Oxidative medicine and cellular longevity. Vol. 1, 9175806. DOI: 10.1155/2017/9175806
25. Chalopin, M., Tesse, A., Martínez, M. C., Rognan, D., Arnal, J.F., Andriantsitohaina, R. (2010). Estrogen receptor alpha as a key target of red wine polyphenols action on the endothelium. PloS one. Vol. 5(1), e8554. DOI: 10.1371/journal.pone.0008554
26. Liskova, A., Samec, M., Koklesova, L., Brockmueller, A., Zhai, K., Abdellatif, B., Kubatka, P. (2021). Flavonoids as an effective sensitizer for anti-cancer therapy: Insights into multi-faceted mechanisms and applicability towards individualized patient profiles. Epma Journal. Vol. 12(2), pp. 155–176. DOI: 10.1007/s13167-021-00242-5
27. Forman, H.J., Davies, K.J., Ursini, F. (2014). How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo. Free Radical Biology and Medicine. Vol. 66, pp. 24–35. DOI: 10.1016/j.freeradbiomed.2013.05.045
28. Hidalgo, M., Sánchez-Moreno, C., de Pascual-Teresa, S. (2010). Flavonoid–flavonoid interaction and its effect on their antioxidant activity. Food chemistry. Vol, 121(3), pp. 691–696. DOI: 10.1016/j. foodchem.2009.12.097
29. Kroon, P.A., Clifford, M.N., Crozier, A., Day, A.J., Donovan, J.L., Manach, C., Williamson, G. (2004). How should we assess the effects of exposure to dietary polyphenols in vitro? The American journal of clinical nutrition. Vol. 80(1), pp. 15–21. DOI: 10.1093/ajcn/80.1.15
30. Esposito, D., Chen, A., Grace, M.H., Komarnytsky, S., Lila, M.A. (2014). Inhibitory effects of wild blueberry anthocyanins and other flavonoids on biomarkers of acute and chronic inflammation in vitro. Journal of Agricultural and Food Chemistry. Vol. 62(29), pp. 7022–7028. DOI: 10.1021/jf4051599
31. Rodriguez-Mateos, A., Rendeiro, C., Bergillos-Meca, T., Tabatabaee, S., George, T.W., Heiss, C., Spencer, J.P. (2013). Intake and time dependence of blueberry flavonoid–induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity. The American journal of clinical nutrition. Vol. 98(5), pp. 1179–1191. DOI: 10.3945/ajcn.113.066639
32. Jana, S., Rastogi, H. (2017). Effects of caffeic acid and quercetin on in vitro permeability, metabolism and in vivo pharmacokinetics of melatonin in rats: potential for herb-drug interaction. European journal of drug metabolism and pharmacokinetics. Vol. 42, pp. 781–791. DOI: 10.1007/s13318-016-0393-7
33. Liang, S., Tian, X., Wang, C. (2022). Nanozymes in the Treatment of Diseases Caused by Excessive Reactive Oxygen Specie. Journal of Inflammation Research. pp. 6307–6328. DOI: 10.2147/JIR. S383239
34. Lotito, S.B., Frei, B. (2004). The increase in human plasma antioxidant capacity after apple consumption is due to the metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids. Free Radical Biology and Medicine. Vol. 37(2), pp. 251– 258. DOI: 10.1016/j.freeradbiomed.2004.04.019
35. Maraldi, T. (2013). Natural compounds as modulators of NADPH oxidases. Oxidative medicine and cellular longevity. Vol. 2013(1), 271602. DOI: 10.1155/2013/271602 29
36. Merry, T.L., Ristow, M. (2016). Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training? The Journal of physiology. Vol. 594(18), pp. 5135–5147. DOI: 10.1113/JP270654
37. Nani, A., Tehami, W. (2023). Targeting inflammasome pathway by polyphenols as a strategy for pancreatitis, gastrointestinal and liver diseases management: an updated review. Frontiers in Nutrition. Vol. 10, 1157572. DOI: 10.3389/fnut.2023.1157572
38. Singh S., Nagalakshmi D., Sharma K.K., Ravichandiran V. (2021). Natural antioxidants for neuroinflammatory disorders and possible involvement of Nrf2 pathway: Heliyon. Vol. 7(2), e06216. Available at: http://creativecommons.org/licenses/ by-nc-nd/4.0/
39. Smiles, W.J., Ovens, A.J., Kemp, B.E., Galic, S., Petersen, J., Oakhill, J. S. (2024). New developments in AMPK and mTORC1 cross-talk. Essays in Biochemistry. Vol. 68(3), pp. 321–336. DOI: 10.1042/EBC20240007
40. Oracz, J., Zyzelewicz, D., Nebesny, E. (2015). The content of polyphenolic compounds in cocoa beans (Theobroma cacao L.), depending on variety, growing region, and processing operations: A review. Critical reviews in food science and nutrition. Vol. 55(9), pp. 1176–1192. DOI: 10.1080/10408398.2012.686934
41. Peluso, I., Raguzzini, A., Serafini, M. (2013). Effect of flavonoids on circulating levels of TNFα and IL6 in humans: a systematic review and metaanalysis. Molecular Nutrition & Food Research. Vol. 57(5), pp. 784–801. DOI: 10.1002/mnfr.201200721
42. Pinheiro, R.G., Pinheiro, M., Neves, A.R. (2021). Nanotechnology innovations to enhance the therapeutic efficacy of quercetin. Nanomaterials. Vol. 11(10), 2658. Available at: https://www.mdpi. com/2079-4991/11/10/2658#
43. Noratto, G.D., Angel-Morales, G., Talcott, S.T., Mertens-Talcott, S.U. (2011). Polyphenolics from acai (Euterpe oleracea Mart.) and red muscadine grape (Vitis rotundifolia) protect human umbilical vascular Endothelial cells (HUVEC) from glucose-and lipopolysaccharide (LPS)-induced inflammation and target microRNA-126. Journal of agricultural and food chemistry. Vol. 59(14), pp. 7999– 8012. DOI: 10.1021/jf201056x
44. Di Lorenzo, C., Colombo, F., Biella, S., Stockley, C., Restani, P. (2021). Polyphenols and human health: The role of bioavailability. Nutrients. Vol. 13(1), 273 p. DOI: 10.3390/nu13010273
45. Villalva, M., Martínez-García, J.J., Jaime, L., Santoyo, S., Pelegrín, P., Pérez-Jiménez, J. (2023). Polyphenols as NLRP3 inflammasome modulators in cardiometabolic diseases: a review of in vivo studies. Food & Function. Vol. 14(21), pp. 9534–9553. DOI: 10.1039/D3FO03015F
46. Ferreira, C., Vieira, P., Sá, H., Malva, J., Castelo-Branco, M., Reis, F., Viana, S. (2024). Polyphenols: Immunonutrients tipping the balance of immunometabolism in chronic diseases. Frontiers in Immunology. Vol. 15, 1360065. DOI: 10.3389/fimmu.2024.1360065
47. Pon Matheswari, P., Jenit Sharmila, G., Murugan, C. (2024). Green synthesis of selenium nanoparticles using Delonix regia and Nerium oleander flower extract and evaluation of their antioxidant and antibacterial activities. Inorganic and Nano-Metal Chemistry. Vol. 54(5), pp. 488–499. DOI: 10.1080/24701556.2021.2025099
48. Wang, B., Wang, S., Ding, M., Lu, H., Wu, H., Li, Y. (2022). Quercetin regulates calcium and phosphorus metabolism through the Wnt signaling pathway in broilers. Frontiers in Veterinary Science. Vol. 8, 786519. DOI: 10.3389/fvets.2021.786519
49. Ren, Q., Sun, S., Zhang, X.D. (2021). Redox-active nanoparticles for inflammatory bowel disease. Nano Research. Vol. 14(8), pp. 2535–2557. DOI: 10.1007/s12274-021-3303-5
50. Sanchez-Garrido, J., Shenoy, A.R. (2021). Regulation and repurposing of nutrient sensing and autophagy in innate immunity. Autophagy. Vol. 17(7), pp. 1571–1591. DOI: 10.1080/15548627.2020.1783119
51. Moroney, M.A., Alcaraz, M.J., Forder, R.A., Carey, F., Hoult, J.R.S. (1988). Selectivity of neutrophil 5-lipoxygenase and cyclo-oxygenase inhibition by an anti-inflammatory flavonoid glycoside and related aglycone flavonoids. Journal of Pharmacy and Pharmacology. Vol. 40(11), pp. 787–792. DOI: 10.1111/j.2042-7158.1988.tb05173.x
52. Sies, H. (2007). Total antioxidant capacity: appraisal of a concept. The Journal of nutrition. Vol. 137(6), pp. 1493–1495. DOI: 10.1093/ jn/137.6.1493
53. Demchenko, A., Bityutskii, V., Tsekhmistrenko, S., Tsekhmistrenko, О., Kharchyshyn, V. (2022). Synthesis of functionalized selenium nanoparticles with the participation of flavonoids. International Science Group. ISG-KONF. Tokyo, Japan, pp. 29–35. DOI: 10.46299/ISG.2022.1.17
54. Pandian, S., Kunjiappan, S., Ravishankar, V., Sundarapandian, V. (2021). Synthesis of quercetin functionalized silver nanoparticles by rapid one-pot approach. BioTechnologia. Vol. 102(1), pp. 75–84. DOI: 10.5114/bta.2021.103764
55. Fang, M.Z., Wang, Y., Ai, N., Hou, Z., Sun, Y., Lu, H., Yang, C.S. (2003). Tea polyphenol (−)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer research. Vol. 63(22), pp. 7563–7570.
56. Huang, Y., Li, W., Su, Z.Y., Kong, A.N.T. (2015). The complexity of the Nrf2 pathway: beyond the antioxidant response. The Journal of nutritional biochemistry. Vol. 26(12), pp. 1401–1413. DOI: 10.1016/j.jnutbio.2015.08.001
57. Arora, I., Sharma, M., Sun, L.Y., Tollefsbol, T.O. (2020). The Epigenetic Link between Polyphenols, Aging and Age-Related Diseases. Genes (Basel). no. 11, 1094. DOI: 10.3390/genes11091094
58. Ferraz, C.R., Carvalho, T.T., Manchope, M.F., Artero, N.A., Rasquel-Oliveira, F.S., Fattori, V., Verri, Jr W.A. (2020). Therapeutic potential of flavonoids in pain and inflammation: mechanisms of action, pre-clinical and clinical data, and pharmaceutical development. Molecules. Vol. 25(3), 762 p. Available at: https://www.mdpi.com/1420-3049/25/3/762#
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