Effectiveness of food concentrate phenolic compounds of apples in experimental membrane pathologies

  • V. P. Fylymonenko National University of Pharmacy
  • L. V. Galuzinska National University of Pharmacy
  • G. B. Kravchenko National University of Pharmacy
  • V. M. Kravchenko National University of PharmacyV. M. Kravchenko
  • Т. О. Bryukhanova Kharkiv National Medical University
  • L. М. Мaloshtan National University of Pharmacy
  • D. V. Lytkin National University of Pharmacy
Keywords: plant polyphenols; antioxidant activity; membrane stabilizing effect; anti-inflammatory effects; capillary-strengthening properties.


Apple fruits are an available source of phenolic compounds that exhibit a wide range of biological activities (antioxidant, anti-inflammatory, membrane stabilizing, etc.). The antioxidant properties of food concentrate phenolic compounds of apples (Concentrate) were studied in vitro in models of spontaneous and ascorbate induced lipid peroxidation (LPO) in rat liver homogenate, and acute carbon tetrachloromethane hepatitis was chosen as in vivo model in rats. Membrane stabilizing activity was evaluated by the degree of hemolysis in blood samples from the tail vein. The effect of Concentrate on vascular permeability was studied considering the time of animal skin papules staining at the site of injection of phlogogenic substances. Hepatoprotective activity in the model of acute carbon tetrachloride hepatitis was assessed by changes in prooxidant-antioxidant status in liver homogenate and liver enzymes activity in serum. Significant antioxidant effect of Concentrate was fixed in models of spontaneous and ascorbate induced LPO (TBA reactants’ content was 3.12 times and 2.25 times lower than control for spontaneous LPO and ascorbate induced LPO, respectively) and under tetrachloride hepatitis (Concentrate antioxidant activity was 47.8%). The membrane-protective activity of the studied Concentrate was also high and reached 50.1%. Also, Concentrate demonstrated capillary-strengthening properties, reducing the permeability of the vascular wall, which was caused by three different chlorogens, most notably by zymosan (Concentrate significantly delayed the stain utilization from the bloodstream by 2.14 times compared to control). Newly developed concentrate showed complex hepatoprotective activity, improving the indices of antioxidant-prooxidant status and activity of liver cytolysis enzymes in rats with tetrachloromethane hepatitis. The transparent corrective effects of Concentrate are the result of synergism and additivity of its multiple components and indicate the prospects of its further research in order to develop medications for the prophylaxis and treatment of diseases associated with membrane damage.


Alkinani, K. B., Ali, E., Al-Shaikh, T. M., Awlia Khan, J. A., Al-Naomasi, T. M., Ali, S. S., Abduljawad, A. A., Mosa, O. F., & Zafar, T. A. (2021). Hepatoprotective effects of (-) epicatechin in CCl4-induced toxicity model are mediated via modulation of oxidative stress markers in rats. Evidence-Based Complementary and Alternative Medicine, 2021, 4655150.

BenSaad, L. A., Kim, K. H., Quah, C. C., Kim, W. R., & Shahimi, M. (2017). Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum. BMC Complementary and Alternative Medicine, 17(1), 47.

Bernatoniene, J., & Kopustinskiene, D. M. (2018). The role of catechins in cellular responses to oxidative stress. Molecules, 23(4), 965.

Birru, R. L., Bein, K., Wells, H., Bondarchuk, N., Barchowsky, A., Di, Y. P., & Leikauf, G. D. (2021). Phloretin, an apple polyphenol, inhibits pathogen-induced mucin overproduction. Molecular Nutrition and Food Research, 65(2), e2000658.

Birru1, R. L., Bein, K., Bondarchuk, N., Wells, H., Lin, Q., Di, Y. P., & Leikauf, G. D. (2021). Antimicrobial and anti-inflammatory activity of apple polyphenol phloretin on respiratory pathogens associated with chronic obstructive pulmonary disease. Frontiers in Cellular and Infection Microbiology, 11, 652944.

Chabanon, M., Stachowiak, J. C., & Rangamani, P. (2017). Systems biology of cellular membranes: A convergence with biophysics. Wiley Interdisciplinary Reviews, Systems Biology and Medicine, 9(5), 1386.

Chang, W. C., Wu, J. S., & Shen, S. C. (2021). Vescalagin from pink wax apple (Syzygium samarangense (Blume) Merrill and Perry) protects pancreatic β-cells against methylglyoxal-induced inflammation in rats. Plants, 10(7), 1448.

Cheng, H., Gang, X., He, G., Liu, Y., Wang, Y., Zhao, X., & Wang, G. (2020). The molecular mechanisms underlying mitochondria-associated endoplasmic reticulum membrane-induced insulin resistance. Frontiers in Endocrinology, 11, 592129.

Cianfruglia, L., Morresi, C., Bacchetti, T., Armeni, T., & Ferretti, G. (2020). Protection of polyphenols against glyco-oxidative stress: Involvement of glyoxalase pathway. Antioxidants, 9(10), 1006.

Clemens, M. M., McGill, M. R., & Apte, U. (2019). Mechanisms and biomarkers of liver regeneration after drug-induced liver injury. Advances in Pharmacology, 85, 241–262.

Gaschler, M. M., & Stockwell, B. R. (2017). Lipid peroxidation in cell death. Biochemical and Biophysical Research Communications, 482(3), 419–425.

Gould, S. B. (2018). Membranes and evolution. Current Biology, 28(8), R381–R385.

Han, M., Zhang, M., Wang, X., Bai, X., Yue, T., & Gao, Z. (2021). Cloudy apple juice fermented by Lactobacillus prevents obesity via modulating gut microbiota and protecting intestinal tract health. Nutrients, 13(3), 971.

Huang, Z. Q., Chen, P., Su, W. W., Wang, Y. G., Wu, H., Peng, W., & Li, P. B. (2018). Antioxidant activity and hepatoprotective potential of quercetin 7-rhamnoside in vitro and in vivo. Molecules, 23(5), 1188.

Irato, P., & Santovito, G. (2021). Enzymatic and non-enzymatic molecules with antioxidant function. Antioxidants, 10(4), 579.

Ito, F., Sono, Y., & Ito, T. (2019). Measurement and clinical significance of lipid peroxidation as a biomarker of oxidative stress: Oxidative stress in diabetes, atherosclerosis, and chronic inflammation. Antioxidants, 8(3), 72.

Kodali, S. T., Kauffman, P., Kotha, S. R., Yenigalla, A., Veeraraghavan, R., Pannu, S. R., Hund, T. J., Satoskar, A. R., McDaniel, J. C., Maddipati, R. K., & Parinandi, N. L. (2020). Oxidative lipidomics: Analysis of oxidized lipids and lipid peroxidation in biological systems with relevance to health and disease. In: Berliner, L. J. (Eds.). Measuring oxidants and oxidative stress in biological systems. Springer Nature. Pp. 61–92.

Koroljuk, M. A., Ivanova, L. I., & Majorova, I. G. (1988). Metod opredelenija aktivnosti katalazy [Method for determining catalase activity]. Laboratory Business, 1, 16–19 (in Russian).

Lee, S. H., Kim, D. H., Kuzmanov, U., & Gramolini, A. O. (2021). Membrane proteomic profiling of the heart: Past, present, and future. American Journal of Physiology, Heart and Circulatory Physiology, 320(1), H417–H423.

Liu, B., Fang, Y., Yi, R., & Zhao, X. (2019). Preventive effect of blueberry extract on liver injury induced by carbon tetrachloride in mice. Foods, 8(2), 48.

Liu, F., Wang, X., Cui, Y., Yin, Y., Qiu, D., Li, S., & Li, X. (2021). Apple polyphenols extract (Ape) alleviated dextran sulfate sodium induced acute ulcerative colitis and accompanying neuroinflammation via inhibition of apoptosis and pyroptosis. Foods, 10(11), 2711.

Liu, W., Wang, Z., Hou, J. G., Zhou, Y. D., He, Y. F., Jiang, S., Wang, Y. P., Ren, S., & Li, W. (2018). The liver protection effects of maltol, a flavoring agent, on carbon tetrachloride-induced acute liver injury in mice via inhibiting apoptosis and inflammatory response. Molecules, 23(9), 2120.

Liu, X., Zhang, Y., Liu, L., Pan, Y., Hu, Y., Yang, P., & Liao, M. (2020). Protective and therapeutic effects of nanoliposomal quercetin on acute liver injury in rats. BMC Pharmacology and Toxicology, 21(1), 11.

Lukitasari, M., Saifur Rohman, M., Nugroho, D. A., Widodo, N., & Nugrahini, N. (2020). Cardiovascular protection effect of chlorogenic acid: Focus on the molecular mechanism. F1000Research, 9, 1462.

Maciejowski, J., & Hatch, E. M. (2020). Nuclear membrane rupture and its consequences. Annual Review of Cell and Developmental Biology, 36, 85–114.

Martini, D., Marino, M., Angelino, D., Del Bo', C., Del Rio, D., Riso, P., & Porrini, M. (2020). Role of berries in vascular function: A systematic review of human intervention studies. Nutrition Reviews, 78(3), 189–206.

Martino, E., Vuoso, D. C., D'Angelo, S., Mele, L., D'Onofrio, N., Porcelli, M., & Cacciapuoti, G. (2019). Annurca apple polyphenol extract selectively kills MDA-MB-231 cells through ROS generation, sustained JNK activation and cell growth and survival inhibition. Scientific Reports, 9(1), 13045.

McGill, M. R., & Jaeschke, H. (2019). Animal models of drug-induced liver injury. Biochimica et Biophysica Acta, Molecular Basis of Disease, 1865(5), 1031–1039.

Mesa-Herrera, F., Taoro-González, L., Valdés-Baizabal, C., Diaz, M., & Marín, R. (2019). Lipid and lipid raft alteration in aging and neurodegenerative diseases: A window for the development of new biomarkers. International Journal of Molecular Sciences, 20(15), 3810.

Muhomedzjanova, S. V., Pivovarov, J. I., Bogdanova, O. V., Dmitrieva, L. A., & Shulunov, A. A. (2017). Lipidy biologicheskih membran v norme i patologii (obzor literatury) [Biological membrane lipids in normal and pathological conditions (literature review)]. Acta Biomedica Scientifica, 117, 43–49 (in Russian).

Ojeaburu, S. I., & Oriakhi, K. (2021). Hepatoprotective, antioxidant and, anti-inflammatory potentials of gallic acid in carbon tetrachloride-induced hepatic damage in Wistar rats. Toxicology Reports, 8, 177–185.

Piccolo, M., Ferraro, M. G., Maione, F., Maisto, M., Stornaiuolo, M., Tenore, G. C., Santamaria, R., Irace, C., & Novellino, E. (2019). Induction of hair keratins expression by an annurca apple-based nutraceutical formulation in human follicular cells. Nutrients, 11(12), 3041.

Popović, D., Kocić, G., Katić, V., Zarubica, A., Veličković, L. J., Ničković, V. P., Jović, A., Veljković, A., Petrović, V., Rakić, V., Jović, Z., Ulrih, N. P., Sokolović, D., Stojanović, M., Stanković, M., Radenković, G., Nikolić, G. R., Lukač, А., Milosavljević, A., & Sokolović, D. (2019). Anthocyanins protect hepatocytes against CCl4-induced acute liver injury in rats by inhibiting pro-inflammatory mediators, polyamine catabolism, lipocalin-2, and excessive proliferation of kupffer cells. Antioxidants, 8(10), 451.

Prohorova, M. I. (1982). Metody biohimicheskih issledovanij (lipidnyj i energeticheskij obmen) [Methods of biochemical research (lipid and energy metabolism)]. Leningrad University Press, Leningrad (in Russian).

Riccio, G., Sommella, E., Badolati, N., Salviati, E., Bottone, S., Campiglia, P., Dentice, M., Tenore, G. C., Stornaiuolo, M., & Novellino, E. (2018). Annurca apple polyphenols protect murine hair follicles from taxane induced dystrophy and hijacks polyunsaturated fatty acid metabolism toward β-oxidation. Nutrients, 10(11), 1808.

Risinger, M., & Kalfa, T. A. (2020). Red cell membrane disorders: Structure meets function. Blood, 136(11), 1250–1261.

Sedlak, L., Wojnar, W., Zych, M., Wyględowska-Promieńska, D., Mrukwa-Kominek, E., & Kaczmarczyk-Sedlak, I. (2018). Effect of resveratrol, a dietary-derived polyphenol, on the oxidative stress and polyol pathway in the lens of rats with streptozotocin-induced diabetes. Nutrients, 10(10), 1423.

Shafi, W., Mansoor, S., Jan, S., Singh, D. B., Kazi, M., Raish, M., Alwadei, M., Mir, J. I., & Ahmad, P. (2019). Variability in catechin and rutin contents and their antioxidant potential in diverse apple genotypes. Molecules, 24(5), 943.

Shimamura, Y., Hirai, C., Sugiyama, Y., Utsumi, M., Yanagida, A., Murata, M., Ohashi, N., & Masuda, S. (2017). Interaction between various apple procyanidin and staphylococcal enterotoxin a and their inhibitory effects on toxin activity. Toxins, 9(8), 243.

Sobeh, M., Hamza, M. S., Ashour, M. L., Elkhatieb, M., El Raey, M. A., Abdel-Naim, A. B., & Wink, M. (2020). A polyphenol-rich fraction from eugenia uniflora exhibits antioxidant and hepatoprotective activities in vivo. Pharmaceuticals, 13(5), 84.

Sommella, E., Badolati, N., Riccio, G., Salviati, E., Bottone, S., Dentice, M., Campiglia, P., Tenore, G. C., Stornaiuolo, M., & Novellino, E. (2019). A boost in mitochondrial activity underpins the cholesterol-lowering effect of annurca apple polyphenols on hepatic cells. Nutrients, 11(1), 163.

Stefanov, O. V. (2001). Doklinichni doslidzhennja likars’kyh zasobiv [Preclinical studies of drugs]. Avicena, Kyiv (in Ukrainian).

Stirpe, M., Palermo, V., Bianchi, M. M., Silvestri, R., Falcone, C., Tenore, G., Novellino, E., & Mazzoni, C. (2017). Annurca apple (M. pumila Miller cv annurca) extracts act against stress and ageing in S. cerevisiae yeast cells. BMC Complementary and Alternative Medicine, 17(1), 200.

Sutcliffe, T. C., Winter, A. N., Punessen, N. C., & Linseman, D. A. (2017). Procyanidin B2 protects neurons from oxidative, nitrosative, and excitotoxic stress. Antioxidants, 6(4), 77.

Visser, J., van Staden, P. J., Soma, P., Buys, A. V., & Pretorius, E. (2017). The stabilizing effect of an oligomeric proanthocyanidin on red blood cell membrane structure of poorly controlled type II diabetes. Nutrition and Diabetes, 7(5), e275.

Voronina, L. M., Desenko, V. F., Kravchenko, V. M., & Saharova, T. S. (1996). Posibnyk do laboratornyh i seminars’kyh zanjat’ z biologichnoji himiji [Manual for laboratory and seminar classes in biological chemistry]. Osnova, Kharkiv (in Ukrainian).

Wang, R., Yang, Z., Zhang, J., Mu, J., Zhou, X., & Zhao, X. (2019). Liver injury induced by carbon tetrachloride in mice is prevented by the antioxidant capacity of anji white tea polyphenols. Antioxidants, 8(3), 64.

Williamson, G. (2017). The role of polyphenols in modern nutrition. Nutrition Bulletin, 42(3), 226–235.

Xiang, Y., Lai, F., He, G., Li, Y., Yang, L., Shen, W., Huo, H., Zhu, J., Dai, H., & Zhang, Y. (2017). Alleviation of rosup-induced oxidative stress in porcine granulosa cells by anthocyanins from red-fleshed apples. PloS One, 12(8), e0184033.

Xu, X., Chen, X., Huang, Z., Chen, D., He, J., Zheng, P., Chen, H., Luo, J., Luo, Y., Yu, B., & Yu, J. (2019). Effects of dietary apple polyphenols supplementation on hepatic fat deposition and antioxidant capacity in finishing pigs. Animals, 9(11), 937.

Yahfoufi, N., Alsadi, N., Jambi, M., & Matar, C. (2018). The immunomodulatory and anti-inflammatory role of polyphenols. Nutrients, 10(11), 1618.

Ydyrys, A., Zhaparkulova, N., Aralbaeva, A., Mamataeva, A., Seilkhan, A., Syraiyl, S., & Murzakhmetova, M. (2021). Systematic analysis of combined antioxidant and membrane-stabilizing properties of several lamiaceae family kazakhstani plants for potential production of tea beverages. Plants, 10(4), 666.

Yoshida, Y., Umeno, A., & Shichiri, M. (2013). Lipid peroxidation biomarkers for evaluating oxidative stress and assessing antioxidant capacity in vivo. Journal of Clinical Biochemistry and Nutrition, 52(1), 9–16.

Yousefi-Manesh, H., Dehpour, A. R., Nabavi, S. M., Khayatkashani, M., Asgardoon, M. H., Derakhshan, M. H., Moradi, S. A., Sheibani, M., Tavangar, S. M., Shirooie, S., Nkuimi Wandjou, J. G., Caprioli, G., Sut, S., Dall'Acqua, S., & Maggi, F. (2021). Therapeutic effects of hydroalcoholic extracts from the ancient apple mela rosa dei monti sibillini in transient global ischemia in rats. Pharmaceuticals, 14(11), 1106.

Zagayko, A., Brjukhanova, T., Lytkin, D., Kravchenko, A., & Fylymonenko, V. (2020). Prospects for using the natural antioxidant compounds in the obesity treatment. IntechOpen.

Zhang, X., Xu, J., Xu, Z., Sun, X., Zhu, J., & Zhang, Y. (2020). Analysis of antioxidant activity and flavonoids metabolites in peel and flesh of red-fleshed apple varieties. Molecules, 25(8), 1968.

Zhu, X., Xu, G., Jin, W., Gu, Y., Huang, X., & Ge, L. (2021). Apple or apple polyphenol consumption improves cardiovascular disease risk factors: A systematic review and meta-analysis. Reviews in Cardiovascular Medicine, 22(3), 835–843.

How to Cite
Fylymonenko, V. P., Galuzinska, L. V., Kravchenko, G. B., Kravchenko, V. M., BryukhanovaТ. О., МaloshtanL. М., & Lytkin, D. V. (2022). Effectiveness of food concentrate phenolic compounds of apples in experimental membrane pathologies . Regulatory Mechanisms in Biosystems, 13(1), 67-72. https://doi.org/10.15421/022209