Author(s):
Nuriddin N. Soliyev, Gulbakhor T. Abdullayeva, Muzaffar I. Asrarov, Gaybullo X. Lutpillaev, Sakhiba D. Madrakhimova, Rakhmatilla N. Rakhimov, Sadbarkhon A. Mavlanova, Ziyofat B. Khosilova
Email(s):
nuriddinsoliyev499@gmail.com
DOI:
10.52711/0974-360X.2025.00261 
Address:
Nuriddin N. Soliyev1, Gulbakhor T. Abdullayeva2, Muzaffar I. Asrarov3, Gaybullo X. Lutpillaev4, Sakhiba D. Madrakhimova4, Rakhmatilla N. Rakhimov5,
Sadbarkhon A. Mavlanova6, Ziyofat B. Khosilova7
1PhD Student of Namangan State University, Uzbekistan.
2Professor of Tashkent State Technical University Named After Islam Karimov, DSc. Uzbekistan.
3Professor of the Institute of Biophysics and Biochemistry at the National University of Uzbekistan, DSc. Uzbekistan.
4PhD student Institutе оf Biооrgаniс Сhеmistrу Nаmеd Аftеr А.S. Sаdikоv. Uzbekistan, Tashkent.
5PhD in Chemical Sciences, Senior Researcher, Institute of Bioorganic Chemistry Named After Acad. A.S. Sadykova ASRUz, Uzbekistan.
6Head of the Department of Physiology of Namangan State University, Ph.D Uzbekistan.
7Karshi State University, Department of Physiology. Uzbekistan.
*Corresponding Author
Published In:
Volume - 18,
Issue - 4,
Year - 2025
ABSTRACT:
Annotation: In this article studied the corrective effect of polyphenol extracts PF-1, isolated from the Karelinia caspia plant and PF-4, isolated from the leaf of quince (Cydonia oblonga), growing in the Republic of Uzbekistan, on the permeability of mPTP in the liver of rats was studied. Studies have shown that polyphenol extracts PF-1 and PF-4(1µg/ml, 5µg/ml, 10µg/ml, 15µg/ml) induce mitochondrial mPTP in the presence of Ca2+ ions. The mPTP inhibitory activities of PF-1 and PF-4 polyphenol extracts ranged from 30% to <83%. The results obtained make it possible to create membrane-active drugs based on extracts of polyphenols PF-1 and PF-4.
Cite this article:
Nuriddin N. Soliyev, Gulbakhor T. Abdullayeva, Muzaffar I. Asrarov, Gaybullo X. Lutpillaev, Sakhiba D. Madrakhimova, Rakhmatilla N. Rakhimov, Sadbarkhon A. Mavlanova, Ziyofat B. Khosilova. Correction of mPTP Dysfunction by some Polyphenol extracts. Research Journal of Pharmacy and Technology. 2025;18(4):1825-0. doi: 10.52711/0974-360X.2025.00261
Cite(Electronic):
Nuriddin N. Soliyev, Gulbakhor T. Abdullayeva, Muzaffar I. Asrarov, Gaybullo X. Lutpillaev, Sakhiba D. Madrakhimova, Rakhmatilla N. Rakhimov, Sadbarkhon A. Mavlanova, Ziyofat B. Khosilova. Correction of mPTP Dysfunction by some Polyphenol extracts. Research Journal of Pharmacy and Technology. 2025;18(4):1825-0. doi: 10.52711/0974-360X.2025.00261 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-4-52
REFERENCES:
1. Zorov D.B., Isaev N.K., Plotnikov E.Yu., Silachev D.N. Prospects of mitochondrial medicine. Biochemistry (Mosc). 2013; Sep; 78(9): 979-90. doi: 10.1134/S0006297913090034.
2. Bonora M., Patergnani S., Ramaccini D., Morciano G., Pedriali G., Kahsay A.E., Bouhamida E., Giorgi C., Wieckowski M.R., Pinton P. Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology. Biomolecules. 2020; 10: 998. doi:10.3390/biom10070998.
3. Bernardi P, von Stockum S. The permeability transition pore as a Ca (2+) release channel: new answers to an old question. Cell Calcium. 2012; Jul; 52(1): 22-7. doi: 10.1016/j.ceca.2012.03.004.
4. Wang W, Fang H, Groom L, Cheng A, Zhang W, Liu J, et al. Superoxide flashes in single mitochondria. Cell. 2008; Jul 25; 134(2): 279-90. doi: 10.1016/j.cell.2008.06.017.
5. Angeli S, Foulger A, Chamoli M, Peiris TH, Gerencser A, Shahmirzadi AA, et al. The mitochondrial permeability transition pore activates the mitochondrial unfolded protein response and promotes aging. eLife. 2021; Sep 1: 10: e63453. doi: 10.7554/eLife.63453.
6. Ding Y, Fang H, Shang W, Xiao Y, Sun T, Hou N, et al. Mitoflash altered by metabolic stress in insulin-resistant skeletal muscle. J Mol Med. 2015; 93: 1119–30. doi:10.1007/s00109-015-1278-y
7. Florian J. Bock., Stephen W. G. Tait. Mitochondria as multifaceted regulators of cell death. Nature Reviews Molecular Cell Biology. 2020; 21: 85–100. https://doi.org/10.1038/ s41580-019-0173-8
8. Ilio Vitale et all. Apoptotic cell death in disease—Current understanding of the NCCD 2023. Cell Death and Differentiation 2023; 30: 1097–1154; https://doi.org/10.1038/s41418-023-01153-w.
9. Galluzzi L., Vitale I., Kepp O., Seror C., Hangen E., et al. Methods to dissect mitochondrial membrane permeabilization in the course of apoptosis. Methods in Enzymology. 2008:442:355-74. doi: 10.1016/S0076-6879(08)01418-3.
10. Zoratti M., Szabo I., Umberto De Marchi. Mitochondrial permeability transition: how many doors to the house? Biochimica et Biophysica Acta (BBA) - Bioenergetics. 2005 Jan 7;1706(1-2):40-52. doi: 10.1016/j.bbabio.2004.10.006.
11. Chinopoulos C. Mitochondrial permeability transition pore: Back to the drawing board. Neurochemistry International. 2018 Jul: 117:49-54. doi: 10.1016/j.neuint.2017.06.010.
12. Alavian K. N., Beutner G., Lazrove E., Sacchetti S., Park H.A., Licznerski P., Li H., Nabili P., Hockensmith K., Graham M., Porter, G.A., Jonas E.S. An uncoupling channel with the c-subunits ring of F1F0 ATP synthase is the mitochondrial permeability transition pore. Proc. Natl. Acad. Sci. USA. 2014 Jul 22;111(29):10580-5. doi: 10.1073/pnas.1401591111.
13. Paolo Bernardi, Christoph Gerle, Andrew P. Halestrap, Elizabeth A. Jonas, Jason Karch, Nelli Mnatsakanyan, Evgeny Pavlov, Shey-Shing Sheu and Alexander A. Soukas. Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions. Cell Death and Differentiation. 2023; Aug; 30(8): 1869-1885. doi: 10.1038/s41418-023-01187-0.
14. JS Armstrong. Mitochondrial Medicine: Pharmacological targeting of mitochondria in disease. British Journal of Pharmacology. 2007; May 21. doi:10.1038/sj.bjp.0707288
15. Robin A J Smith, Richard C Hartley, Michael P Murphy. Mitochondria-targeted small molecule therapeutics and probes. Antioxidants and Redox Signaling. 2011; Dec 15; 15(12): 3021-38. doi: 10.1089/ars.2011.3969.
16. Aarti Singha, Danilo Faccendaa. Michelangelo Campanellaa, Pharmacological advances in mitochondrial therapy. EBioMedicine. 2021; Mar: 65: 103244. doi: 10.1016/j.ebiom. 2021.103244.
17. Anna Olszewska, Adam Szewczyk. Mitochondria as a pharmacological target: Magnum overview. International Union of Biochemistry and Molecular Biology Life. 2013; Mar; 65(3): 273-81. doi:10.1002/iub.1147.
18. Novikov V.E, Levchenkova O.S, Pozhilova E.V. Mitochondrial nitric oxide synthase and its role in the mechanisms of cell adaptation to hypoxia. Reviews on Clinical Pharmacology and Drug Therapy. 2016. doi: 10.17816/RCF14238-46
19. Jyotsna Mishra, Ariea J. Davani, Gayathri K. Natarajan, Wai-Meng Kwok, David F. Stowe and Amadou K.S Camara. Cyclosporin A Increases Mitochondrial Buffering of Calcium: An Additional Mechanism in Delaying Mitochondrial Permeability Transition Pore Opening. 2019; Sep 7; 8(9): 1052. doi: 10.3390/cells8091052.
20. Jennifer R. Hom, Rodrigo A. Quintanilla, David L. Hoffman, Karen L. The Permeability Transition Pore Controls Cardiac Mitochondrial Maturation and Myocyte Differentiation. Developmental Cell. 2011; Sep 13; 21(3): 469-78. doi: 10.1016/j.devcel.2011.08.008.
21. Makoto Naoi, Yuqiu Wu, Masayo Shamoto-Nagai, Wakako Maruyama. Mitochondria in Neuroprotection by Phytochemicals: Bioactive Polyphenols Modulate Mitochondrial Apoptosis System, Function and Structure. International Journal of Molecular Sciences. 2019; May 17; 20(10): 2451. doi: 10.3390/ijms20102451.
22. Mohammad Waseem, Bi-Dar Wang. Promising Strategy of mPTP Modulation in Cancer Therapy: An Emerging Progress and Future Insight. International Journal of Molecular Sciences. 2023; 24: 5564. https://doi.org/10.3390/ ijms24065564
23. Haumann J, Dash R.K, Stowe D.F, Boelens A.D, Beard D.A, Camara A.K. Mitochondrial free [Ca2+] increases during ATP/ADP antiport and ADP phosphorylation: Exploration of mechanisms. Biophysical Journal. 2010; Aug 9; 99(4): 997-1006. doi: 10.1016/j.bpj.2010.04.069.
24. Sokolova N, Pan S, Provazza S, Beutner G, Vendelin M, Birkedal R, Sheu S.S. ADP protects cardiac mitochondria under severe oxidative stress. PLOS one. 2013; Dec 13. doi:10.1371/journal.pone.0083214
25. Natalia V. Naryzhnaya, Leonid N. Maslov, Peter R. Oeltgen. Pharmacology of mitochondrial permeability transition pore inhibitors. Drug Development Research. 2019; Dec; 80(8): 1013-1030. doi: 10.1002/ddr.21593. Epub 2019 Aug 24.
26. Asrarov M.I., Shkinev A.V., Pozilov M.K., Ergashev N.A. The effect of the diterpenoid salvifolin on the state of the mitochondrial pore of the heart of rats with alloxan-induced diabetes. Problems of biological, medical and pharmaceutical chemistry. 2018; 21: 44-48 doi: 10.29296/25877313-2018-02-06
27. Muratova D.Kh, Ergashev N.A, Shkinev A.V, Asrarov M.I, Kurbanov U.K. The effects of songorine on the activity of the ATP-dependent K+-channel and the state of the megapore of rat liver mitochondria. Exp. Clin. Phar., 2021; 84: 12-15 (in Russian language).
28. Lubomira Protasyuk. Mitochondrial Pharmacology – the Future of Drug Therapy. 2022 year https://thepharma.media/medicine/30584-mitoxondrialnaya-farmakologiya-budushhee-lekarstvennoi-terapii
29. Zorov D.B., Juhaszova M., Yaniv Y., Nuss H.B., Wang S., and Sollott S.J. Regulation and pharmacology of the mitochondrial permeability transition pore. Cardiovascular Research 2009; 83: 213–225. doi:10.1093/cvr/cvp151
30. Novikov V.E., Levchenkova O.S. New directions of search for drugs with antihypoxic activity and targets for their action. Experimental and Clinical Pharmacology. 2013; 76(5): 37-47 doi: https://doi.org/10.30906/0869-2092-2013-76-5-37-47
31. Levchenkova O.S., Novikov V.E., Pozhilova E.V. Mitochondrial pore as a pharmacological target. Bulletin of the Smolensk State Medical Academy 2014; 13(4): 24-33.
32. Ishimov U.J., Abdullayeva G.T., Ziyavitdinov J.F., Asrоrov A.M., Ergashev N.A., Asrarov M.I. The effects of isoleted fractions of red pepper Capsicum annuum L. on the mitochondrial permeability transition pore and and lipid pereoxidation. Journal of Microbiology, Biotechnology and Food Sciences. 2016; 05(03): 259-262. doi:10.15414/jmbfs.2015/16.5.3.259-262
33. Abenaa Serwaa Achampong, Augustine Ocloo, Regina Appiah-Opong. Effects of selected medicinal plant extracts on mitochondrial function. Biofarmasi Journal of Natral Product Biochemistry. 2019; 17(1): 1-13, DOI: 10.13057/biofar/f170101
34. Zbigniev Balion, Kristina Ramanauskiene, Aiste Jekabson, Daiva Majiene. The Role of Mitochondria in Brain Cell Protection from Ischaemia by Differently Prepared Propolis Extracts. Antioxidants 2020; 9: 1262. doi:10.3390/antiox9121262. www.mdpi.com/journal/antioxidants
35. Cristian Sandoval-Acuña, Jorge Ferreira, Hernán Speisky. Polyphenols and mitochondria: An update on their increasingly emerging ROS-scavenging independent actions. Archives of Biochemistry and Biophysics. 2014; Oct 1: 559: 75-90. doi: 10.1016/j.abb.2014.05.017. Epub 2014 May 27.
36. T Leila Chodari, Mutlu Dilsiz Aytemir, Parviz Vahedi, Mahdieh Alipour, Sepideh Zununi Vahed, Seyed Mahdi Hosseiniyan Khatibi, Elham Ahmadian, Mohammadreza Ardalan and Aziz Eftekhar. Targeting Mitochondrial Biogenesis with Polyphenol Compounds. Oxidative Medicine and Cellular Longevity. 2021; Jul 12: 2021: 4946711. doi: 10.1155/2021/4946711. eCollection 2021.
37. Gulbahor T. Abdullayeva, Marguba J. Toshtemirova, Muzaffar I. Asrarov. Antihypoxic activity of getasane polyphenols in experimental hemic hypoxia. BioGecko. Journal for New Zealand Herpetology. 2023; 12(3): 2023. doi: http://biogecko.co.nz/.2023.v12.i03.pp2945-2949
38. Абдуллаева Г.Т., Гайибов У.Г., Абдуллаева М.М., Абдуллажанова Н.Г., Асраров М.И., Назаров К.К. Antiradical activity of some polyphenol compounds. Universum: химия и биология. –2019. – No. 8/62. – С. 10-14.
39. Oliveira M. R., Nabavi S. M., Braidy N., Setzer W. N., Ahmed T., Nabavi S. F. Quercetin and the mitochondria: a mechanistic view. Biotechnology Advances. 2016; 34(5): 532-549. doi: 10.1016/j.biotechadv.2015.12.014.
40. Qiu L., Luo Y., Chen X. Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats. Biomedicine and Pharmacotherapy. 2018 Jul: 103: 1585-1591. doi: 10.1016/j.biopha.2018.05.003.
41. Zhang Q., Cheng G., Pan J., Zielonka J., Xiong D., Myers C. R., et al. Magnolia extract is effective for the chemoprevention of oral cancer through its ability to inhibit mitochondrial respiration at complex I. Cell Commun. Signal. 2020 Apr 7;18(1):58. doi: 10.1186/s12964-020-0524-2.
42. Zhang Z., Shi J., Nice E. C., Huang C., Shi Z. The multifaceted role of flavonoids in cancer therapy: Leveraging autophagy with a double-edged sword. Antioxidants 2021; 10(7): 1138. https://doi.org/10.3390/antiox10071138
43. Newman D. J., Cragg G. M. Natural products as sources of new drugs from 1981 to 2014. Journal of Natural Products. 2016, 79, 3, 629–661 doi: 10.1021/acs.jnatprod.5b01055
44. Yuan H., Ma Q., Ye L., Piao G. The traditional medicine and modern medicine from natural products. Molecules. 2016; Apr 29; 21(5): 559. doi: 10.3390/molecules21050559.
45. Andrew P Halestrap. What is the mitochondrial permeability transition pore? Journal of Molecular and Cellular Cardiology. 2009 Jun; 46(6): 821-31. doi: 10.1016/j.yjmcc.2009.02.021.
46. Andrew P Halestrap. A pore way to die: the role of mitochondria in reperfusion injury and cardioprotection. Biochemical Society Transactions. 2010 Aug;38(4):841-60. doi: 10.1042/BST0380841.
47. Schneider W.C., Hogeboom G.H. Cytochemical studies of mammalian tissues: the isolation of cell components by differential centrifugation. Cancer. Res. 1951; 11(1): 1–22.
48. Peterson G.L. A simplification of the protein assay method of Lowry et al. which is more generally applicable. Analytical Biochemistry. 1977; Dec; 83(2): 346-56. doi: 10.1016/0003-2697(77)90043-4
49. Lihua He, John J. Lemasters. Regulated and unregulated mitochondrial permeability transition pores: a new paradigm of pore structure and function? FEBS Letters. 2002 Feb 13; 512(1-3): 1-7. doi: 10.1016/s0014-5793(01)03314-2.
50. V.E. Novikov, O.S. Levchenkova. Mitochondrial targets for pharmacological regulation of cell adaptation to hypoxia. Reviews of Clinical Pharmacology and Drug Therapy. 2014; 12: 28-35.
51. Ших Е.В. Биодоступность пероральных препаратов. РМЖ. 2007; 2:95.
52. Popova N.V., Potoroko I.Yu. Increase of efficiency of biologically active substance extraction from vegetable raw material by ultrasonic treatment. Bulletin of the South Ural State University. Ser. Food and Biotechnology. 2018; 6(1): 14–22. doi: 10.14529/food180102
53. Prichko T.G., Droficheva N.B. Japonica (henomelis mauleya) – biologically valuable raw material for producing food functionality. A healthy food – the basis of the Nation's health. 2014; 9: 25–27.
54. Al-Zughbi, I., Krayem, M. Quince fruit Cydonia oblonga Mill nutritional composition, antioxidative properties, health benefits and consumers preferences towards some industrial quince products: A review. Food Chemistry. 2022; 393: 133362 https://doi.org/10.1016/j.foodchem.2022.133362
55. Montero M., Alonso M.T., Carnicero E., Cuchillo-Ibanez I., Albillos A., Garcia A.G., Garcia-Sancho, J., Alvarez J. Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+ transients that modulate secretion. Nature Cell Biology. 2000; Feb; 2(2): 57-61. doi: 10.1038/35000001.
56. Tewari D., Ahmed T., Chrirasani V.R., Singh P.K., Maji S.M., Senapati S., Bera A.K. Modulation of the mitochondrial voltage dependent anion channel (VDAC) by curcumin. Biochimica et Biophysica Acta. 2015; Jan; 1848(1PtA): 151-8. doi: 10.1016/j.bbamem.2014.10.014.