Tannins as Modulators in the Prevention of Mitochondrial Dysfunction

Authors

  • Abdulkhakova Gulnazira Vakhobjonovna Institute of Biophysics and Biochemistry, The National University of Uzbekistan, Tashkent, Uzbekistan
  • Komilov Esokhon Jurayevich Institute of Biophysics and Biochemistry, The National University of Uzbekistan, Tashkent, Uzbekistan
  • Abdullaev Izzatullo Ziyoyiddin Ogli A. S. Sadykov Institute of Bioorganic Chemistry, The Academy of Sciences of the Republic of Uzbekistan, Tashkent, Uzbekistan
  • Ergashev Nurali Azamovich A. S. Sadykov Institute of Bioorganic Chemistry, The Academy of Sciences of the Republic of Uzbekistan, Tashkent, Uzbekistan
  • Makhmudov Rustamjon Rasuljonovich A. S. Sadykov Institute of Bioorganic Chemistry, The Academy of Sciences of the Republic of Uzbekistan, Tashkent, Uzbekistan
  • Asrarov Muzaffar Islomovich Institute of Biophysics and Biochemistry, The National University of Uzbekistan, Tashkent, Uzbekistan

DOI:

https://doi.org/10.48048/tis.2025.10436

Keywords:

2,2-diphenyl-1-picrylhydrazyl (DPPH), Hydrolysable tannins, Lipid peroxidation (LPO), Mitochondrial ATP dependent potassium (mitoKATP) channel, Mitochondrial membrane, Mitochondrial permeability transition pore (MPTP), Nonagalloyl glucose, Octagalloyl glucose, Pistacia vera L.

Abstract

In this article, the effects of octagalloyl-glucose and nonagalloyl-glucose hydrolyzable tannins isolated from the leaves of Pistacia vera L., a plant of the Anacardiaceae family, on lipid peroxidation (LPO), mitochondrial permeability transition pore (mPTP) status, and ATP-dependent K+ (mitoKATP) channel activity in mitochondria, which are directly involved in various pathologies, as well as their antiradical properties were studied in vitro. In vitro experiments showed that octagalloyl-glucose and nonagalloyl-glucose tannins inhibited the Fe2+/ascorbate-induced LPO process in mitochondria by 86.7 ± 4.4% and 85.5 ± 4%, respectively, at a concentration of 10 μM, while they blocked mitochondrial mPTP by 88.2 ± 4.5% and 90.3 ± 5.1%, respectively, at a concentration of 15 μM in succinate + rotenone medium. MitoKATP-channel of rat liver mitochondria was activated by octagalloyl-glucose at 10 μM concentration by 90.9 ± 2.6%, nonagalloyl-glucose at 5 μM concentration by 84.2 ± 1.8%, but at 10 μM concentration, it was able to activate by 50.5 ± 5.3%. Octagalloyl-glucose and nonagalloyl-glucose tannins at a concentration of 15 μM neutralized DPPH radical by 91.7 ± 1.83% and 85.9 ± 3.5%, respectively. According to the obtained results, taking into account that the high antiradical and antioxidant activity of the studied hydrolyzable tannins (octagalloyl-glucose and nonagalloyl-glucose) at low concentrations have a stabilizing effect on the mitochondrial membrane, it is possible to conduct additional experiments that allow creating membrane-active preparations from them.

HIGHLIGHTS

  • Hydrolyzable tannins (octagalloyl- and nonagalloyl-glucose) were isolated from Pistacia vera L. leaves.
  • Both compounds significantly inhibited Fe²⁺/ascorbate-induced mitochondrial lipid peroxidation in vitro.
  • Octagalloyl- and nonagalloyl-glucose effectively blocked mitochondrial permeability transition pore (mPTP) opening.
  • Activation of ATP-sensitive mitochondrial potassium (mitoKATP) channels was concentration-dependent.
  • Both tannins exhibited high DPPH radical scavenging activity, indicating potent antioxidant properties.
  • Results support their potential use as membrane-stabilizing, antioxidant therapeutic agents.

GRAPHICAL ABSTRACT

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References

OS Ademowo, HKI Dias, DGA Burton and HR Griffiths. Lipid (per) oxidation in mitochondria: An emerging target in the ageing process? Biogerontology. 2017; 18(6), 859-879.

M Xiao, H Zhong, L Xia, Y Tao and H Yin. Pathophysiology of mitochondrial lipid oxidation: Role of 4-hydroxynonenal (4-HNE) and other bioactive lipids in mitochondria. Free Radical Biology and Medicine 2017; 111, 316-327.

PR Angelova, N Esteras and AY Abramov. Mitochondria and lipid peroxidation in the mechanism of neurodegeneration: Finding ways for prevention. Medicinal Research Reviews 2021; 41(2), 770-784.

R Endlicher, Z Drahota, K Stefkova, Z Cervinkova and O Kucera. The mitochondrial permeability transition pore—current knowledge of its structure, function, and regulation, and optimized methods for evaluating its functional state. Cells 2023; 12(9), 1273.

Nozim N. Khoshimov, Alisher A. Mukhtorov, Kabil E. Nasirov, Rakhmatilla N. Rakhimov, Rahmatjon R. Mamadaminov. Effects of Polyphenols on changes in the transport of Ca2+ NMDA-receptors under the influence of L-glutamate. Research Journal of Pharmacy and Technology 2023; 16(3):1205-3.

MR Rasuljonovich, SG Gaybullaevna, AN Tillakhodjaevna and DM Ravshanbekovna. Isolation of tannins from Pistacia vera. Science and Innovation International Scientific Journal 2023; 2(10), 80-88.

FAO. Directive 2010/63/EU on the protection of animals used for scientific purposes. Official Journal of the European Union, Luxembourg, Luxembourg, 2010.

WC Schneider and GH Hogeboom. Cytochemical studies of mammalian tissues: The isolation of cell components by differential centrifugation. Cancer Research 1951; 11(1), 1-22.

Y Umidakhon, B Erkin, G Ulugbek, N Bahadir and A Karim. Correction of the mitochondrial NADH oxidase activity, peroxidation and phospholipid metabolism by haplogenin-7-glucoside in hypoxia and ischemia. Trends in Sciences 2022; 19(21), 6260.

MI Asrarov, EJ Komilov and Ergashev. The mechanism of action of flavone luteolin on the function of rat liver mitochondria. Problems of Biological Medical and Pharmaceutical Chemistry 2015; 12, 38-43.

TV Pochinok, ML Tarakhovsky and VA Portnyagina. A rapid method for determination of antioxidative activity of drugs. Pharmaceutical Chemistry Journal 1985; 5, 565-569.

UG Gayibov, SN Gayibova, MK Pozilov, FS Tuxtaeva, UR Yusupova, GMK Djabbarova, ZA Mamatova, NA Ergashev and TF Aripov. Influence of quercetin and dihydroquercetin on some functional parameters of rat liver mitochondria. Journal of Microbiology Biotechnology and Food Sciences 2021; 11(1), e2924.

OB Vadziuk and SA Kosterin. Diazoxide-induced mitochondrial swelling in the rat myometrium as a consequence of the activation of the mitochondrial ATP-sensitive (K+)-channel. Ukrainskii Biokhimicheskii Zhurnal 2008; 80(5), 45-51.

DD Esposti, J Hamelin, N Bosselut, R Saffroy, M Sebagh, A Pommier, C Martel and A Lemoine. Mitochondrial roles and cytoprotection in chronic liver injury. Biochemistry Research International 2012; 2012(1), 387626.

NK Nozim, BK Islom, UDJ Ismoil, SK Siroj, UMA Abdugafor, OMM Ugli, EN Kabil, MZ Amindjanovna, SG Abdullayevna and NR Rakhmatilla. Еffесt of Pоlyphеnоls on Сhаngеs in thе Hеmоstаtiс Systеm of Blооd Plаsmа in Hеаlthy and Mоdеl Rаts with Аlzhеimеr’s Disеаsе. Trends in Sciences 2024; 21(9), 8081.

IZOGL Abdullaev, UG Gayibov, SZ Omonturdiev, SF Azamjonovna, SN Gayibova and TF Aripov. Molecular pathways in cardiovascular disease under hypoxia: Mechanisms, biomarkers, and therapeutic targets. Journal of Biomedical Research 2025; 39, 1-16.

F Palmieri and M Monne. Discoveries, metabolic roles and diseases of mitochondrial carriers: A review. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2016; 1863(10), 2362-2378.

JJ Ruprecht and ERS Kunji. Structural mechanism of transport of mitochondrial carriers. Annual Review of Biochemistry 2021; 90, 535-558.

UG Gayibov, SN Gayibova, HM Karimjonov, AA Abdullaev, DS Abduazimova, RN Rakhimov, HS Ruziboev, MA Xolmirzayeva, AE Zaynabiddinov and TFA Aripov. Antioxidant and cardioprotective properties of polyphenolic plant extract of Rhus glabra L. Plant Science Today. 2024; 11(3), 1-8.

M Zaripova, SN Gayibova, RR Makhmudov, AA Mamadrahimov, NL Vypova, UG Gayibov, SM Miralimova and TF Aripov. Characterization of rhodiola heterodonta (crassulaceae): Phytocomposition, antioxidant and antihyperglycemic activities. Preventive Nutrition and Food Science 2024; 29(2), 135-145.

DJ Robichaux, M Harata, E Murphy and J Karch. Mitochondrial permeability transition pore-dependent necrosis. Journal of Molecular and Cellular Cardiology 2023; 174, 47-55.

Z Shakiryanova, R Khegay, U Gayibov, A Saparbekova, Z Konarbayeva, A Latif and O Smirnova. Isolation and study of a bioactive extract enriched with anthocyanin from red grape pomace (Cabernet Sauvignon). Agronomy Research 2023; 21(3), 1293-1303.

TF Aripov, UG Gayibov, SN Gayibova, AA Abdullaev, DSK Abduazimova, YI Oshchepkova and SI Salikhov. In vitro antioxidant and antiradical activity of the total polyphenols (substances of the antiviral drug rutan) of the leaves of tannic sumach rhus coriaria L. Chemistry of Plant Raw Material 2024; 4, 138-147.

IA Najar, GD Singh, S Javed and RK Johri. Effect of some phytoconstituents on Fe2+/ascorbate-induced lipid peroxidation. Indian Journal of Experimental Biology 2016; 54(12), 851-855.

UG Gayibov, EJ Komilov, RN Rakhimov, NA Ergashev, NG Abdullajanova, MI Asrorov and TF Aripov. Influence of new polyphenol compound from Euphorbia plant on mitochondrial function. Journal of Microbiology Biotechnology and Food Sciences 2019; 8(4), 1021.

N Ergashev, K Sayfieva, R Makhmudov and M Asrarov. Effect of tannins isolated from Plantago major L. and Plantago lanceolata L. on mitochondrial permeability transition pore in rat liver. Trends in Sciences 2024; 21(7), 7661.

DR Isamukhamedova, NA Ergashev, RN Rakhimov and MI Asrarov. Effect of hydrolyzable tannins of Euphorbia plants on the rat antioxidant system under oxidative stress. International Journal of Biochemistry Research & Review 2024; 33(2), 40-46.

DK Muratova, NA Ergashev, JJ Sobirov, UK Kurbanov and MI Asrarov. Effect of diterpene alkaloids on lipid peroxidation in mitochondria. Nova Biotechnological et Chimica 2021; 20(2), e850.

BG Yuldoshev, NA Ergashev, EJ Komilov, DR Siddiqov and KS Ruziboyev. The effect of kaempferol and its glycosides on the lipid peroxidation of mitochondria. Proceedings of the Russian Academy of Sciences 2022; 5, 78-82.

Guli M. Raimova, Nozim N. Khoshimov, Kabil E. Nasirov, Abbaskhan S. Тuraev, Malokhat E. Savutova. Anti-thrombotic action of sulfated polysaccharides on thrombosis caused by thromboplastin. Research Journal of Pharmacy and Technology. 2021; 14(11):6085-8.

AV Mahmudov, OS Abduraimov, SB Erdonov, UG Gayibov and LY Izotova. Bioecological features of Nigella sativa L. in different conditions of Uzbekistan. Plant Science Today 2022; 9(2), 421-426.

AV Mahmudov, OS Abduraimov, SB Erdonov, AL Allamurotov, OT Mamatqosimov, UG Gayibov and L Izotova. Seed productivity of Linum usitatissimum L. in different ecological conditions of Uzbekistan. Plant Science Today 2022; 9(4), 1090-1101.

N Ergashev, D Isamukhamedova, K Sayfieva, U Gayibov, R Rakhimov, R Makhmudov and M Asrarov. Anti-radical activity of some hydrolyzable tannins. Universum Chemistry & Biology 2023; 7, 109.

A Abdullaev, I Abdullaev, A Bogbekov, U Gayibov, S Omonturdiev, S Gayibova, M Turahodjayev, K Ruziboev and T Aripov. Antioxidant potential of rhodiola heterodonta extract: Activation of Nrf2 pathway via integrative in vivo and in silico studies. Trends in Sciences 2025; 22(5), 9521.

S Sekowski, A Veiko, E Olchowik-Grabarek, A Dubis, AZ Wilczewska, KH Markiewicz, IB Zavodnik, E Lapshina, I Dobrzynska, N Abdulladjanova and M Zamaraeva. Hydrolysable tannins change physicochemical parameters of lipid nano-vesicles and reduce DPPH radical - Experimental studies and quantum chemical analysis. Biochimica et Biophysica Acta - Biomembranes 2022; 1864(1), 183778.

M Carraro and P Bernardi. Calcium and reactive oxygen species in regulation of the mitochondrial permeability transition and of programmed cell death in yeast. Cell Calcium 2016; 60(2), 102-107.

Y Kamei, M Koushi, Y Aoyama and R Asakai. The yeast mitochondrial permeability transition is regulated by reactive oxygen species, endogenous Ca²⁺, and Cpr3, mediating cell death. Biochimica et Biophysica Acta - Bioenergetics 2018; 1859(12), 1313-1326.

R Toczylowska-Maminska, A Olszewska, M Laskowski, P Bendnarczyk, K Skowronek and A Szewczyk. Potassium channel in the mitochondria of human keratinocytes. Journal of Investigative Dermatology 2014; 134(3), 764-772.

Nozim N. Khoshimov, Guli M. Raimova, Kabul E. Nasirov, Zulayho A. Mamatova, Nodira I. Mamadaliyeva, Abbaskhan S. Тuraev. The effect of Sulphated cellulose on System of Haemostasis. Research Journal of Pharmacy and Technology. 2021; 14(6):3283-9.

GD Mironova, EV Kachaeva and AT Kopylov. Mitochondrial ATP-dependent potassium channel. I. The structure of the channel, the mechanisms of its functioning and regulation. Vestnik Rossiiskoi akademii meditsinskikh nauk 2007; 2, 34-43.

GD Mironova, MI Shigaeva, NV Belosludtseva, EN Gritsenko, KN Belosludtsev, EL Germanova and LD Lukyanova. Effect of several flavonoid-containing plant preparations on activity of mitochondrial ATP-dependent potassium channel. Bulletin of Experimental Biology and Medicine 2008; 146(2), 229-233.

D Inomjonov, I Abdullaev, S Omonturdiev, A Abdullaev, L Maxmudov, M Zaripova, M Abdullayeva, M Abduazimova, D Menglieva, S Gayibova, M Sadbarxon, U Gayibov and T Aripov. In vitro and in vivo studies of crategus and inula helenium extracts: Their effects on rat blood pressure. Trends in Sciences 2025; 22(3), 9158.

O Gaibullayeva, A Islomov, D Abdugafurova, B Elmurodov, B Mirsalixov, L Mahmudov, I Adullaev, K Baratov, S Omonturdiev and S Sa'dullayeva. Inula helenium L. root extract in sunflower oil: Determination of its content of water-soluble vitamins and immunity-promoting effect. Biomedical and Pharmacology Journal 2024; 17(4), 2729-2737.

AQQ Azimova, AX Islomov, SA Maulyanov, DG Abdugafurova, LU Mahmudov, IZO Abdullaev, AS Ishmuratova, SQQ Siddikova and IP Askarov. Determination of vitamins and pharmacological properties of Vitis vinifera L. plant fruit part (mixed varieties) syrup-honey. Biomedical and Pharmacology Journal 2024; 17(4), 2779-2786.

OS Zoirovich, AIZ Ugli, ID Raxmatillayevich, ML Umarjonovich, ZM Ravshanovna, GS Narimanovna, GU Gapparjanovich and AT Fatikhovich. The effect of ajuga turkestanica on the rat aortic smooth muscle ion channels. Biomedical and Pharmacology Journal 2024; 17(2), 1213-1222.

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Published

2025-06-30