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The protective effect of grape seed extract (Vitis vinifera) against mesenteric ischemia/reperfusion injury in rats: an in vivo, in vitro and molecular docking study

Year 2023, Volume: 27 Issue: 4, 1513 - 1523, 28.06.2025

Abstract

In this study, we aimed to determine the protective effect of grape seed extract against mesenteric ischemia/reperfusion (I/R) injury in rats. In addition, an in silico molecular docking study was performed to compare the effects of natural compounds in grape seed extract on myeloperoxidase (MPO) enzyme at the molecular level. In addition to MPO activity, malondialdehyde (MDA) and glutathione (GSH) activities were also measured in the intestinal tissue samples. Serum cytokines, TNF-α and IL-1β, were measured to assess systemic tissue damage. Mesenteric GSH decreased significantly after ischemia/reperfusion, while MDA levels and MPO activity increased significantly. Binding interactions were detected by the binding mode of analysis, and the study compared the binding affinities of compounds at the active site of myeloperoxidase and glutathione peroxidase. As a result, it was found that procyanidins (B1-B4), which are predominantly present in GS extract, have the highest binding affinity and molecular interaction.

References

  • [1] Tran LM, Andraska E, Haga L, Sridharan N, Chaer RA, Eslami MH. Hospital-based delays to revascularization increase risk of postoperative mortality and short bowel syndrome in acute mesenteric ischemia. J Vasc Surg. 2022;75(4):1323-1333. https://doi.org/10.1016/j.jvs.2021.09.033
  • [2] Florim S, Almeida A, Rocha D, Portugal P. Acute mesenteric ischaemia: a pictorial review. Insights Imaging. 2018;9(5):673-682. https://doi.org/10.1007/s13244-018-0641-2
  • [3] Gul MO, Akyuz C, Sunamak O, Ogunc AV, Sehirli AO. Effects of Saint John’s Wort extract on intestinal injury and apoptosis. Ann Med Res. 2021;28(9):1725-1730. https://doi.org/10.5455/annalsmedres.2020.11.1096
  • [4] Katseni K, Chalkias A, Kotsis T, Dafnios N, Arapoglou V, Kaparos G, Logothetis E, Iacovidou N, Karvouni E, Katsenis K. The effect of perioperative ıschemia and reperfusion on multiorgan dysfunction following abdominal aortic aneurysm repair. Biomed Res Int.2015;2015:598980. https://doi.org/10.1155/2015/598980
  • [5] Sehirli O, Ozel Y, Dulundu E, Topaloglu U, Ercan F, Sener G. Grape seed extract treatment reduces hepatic ischemia-reperfusion injury in rats. Phytother Res. 2008;22(1):43-48. https://doi.org/10.1002/ptr.2256
  • [6] Sharifi-Rad M, Anil Kumar NV, Zucca P, Varoni EM, Dini L, Panzarini E, Rajkovic J, Fokou PVT, Azzini E, Peluso I, Mishra AP, Nigam M, Rayess YE, Beyrouthy ME, Polito L, Iriti M, Martins N, Martorell M, Docea AO, Setzer WN, Calina D, Cho WC, Sharifi-Rad J. Lifestyle, oxidative stress, and antioxidants: Back and forth in the pathophysiology of chronic diseases. Front Physiol. 2020;11:694. https://doi.org/10.3389/fphys.2020.00694
  • [7] Sadžak A, Mravljak J, Maltar-Strmečki N, Arsov Z, Baranović G, Erceg I, Kriechbaum M, Strasser V, Pribly J, Segota S. The structural ıntegrity of the model lipid membrane during induced lipid peroxidation: The role of flavonols in the inhibition of lipid peroxidation. Antioxidants (Basel). 2020;9(5):430. https://doi.org/10.3390/antiox9050430
  • [8] Gil-Cardoso K, Comitato R, Ginés I, Ardévol A, Pinent M, Virgili F, Terra Ximena, Blay M. Protective effect of proanthocyanidins in a rat model of mild intestinal inflammation and impaired intestinal permeability induced by LPS. Mol Nutr Food Res. 2019;63(8):e1800720. https://doi.org/10.1002/mnfr.201800720
  • [9] Kadri S, El Ayed M, Limam F, Aouani E, Mokni M. Preventive and curative effects of grape seed powder on stroke using in vitro and in vivo models of cerebral ischemia/reperfusion. Biomed Pharmacother. 2020;125:109990. https://doi.org/10.1016/j.biopha.2020.109990
  • [10] Zhan J, Wang K, Zhang C, Zhang C, Li Y, Zhang Y, Li Y, Zhang Y, Chang X, Zhou Q, Yao Y, Liu Y, Xu G. GSPE Inhibits HMGB1 release, attenuating renal IR-induced acute renal injury and chronic renal fibrosis. Int J Mol Sci. 2016;17(10):1647. https://doi.org/10.3390/ijms17101647
  • [11] Shao ZH, Wojcik KR, Dossumbekova A, Hsu C, Mehendale SR, Li CQ, Qin Y, Sharp WW, Chang WT, Hamann KJ, Yuan CS, Hoek TLV. Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling. J Cell Biochem. 2009;107(4):697-705. https://doi.org/10.1002/jcb.22170
  • [12] Gori F, Fumagalli J, Lonati C, Caccialanza R, Zanella A, Grasselli G. Ascorbic acid in solid organ transplantation: A literature review. Clin Nutr. 2022;41(6):1244-1255. https://doi.org/10.1016/j.clnu.2022.04.004
  • [13] Luther B, Mamopoulos A, Lehmann C, Klar E. The ongoing challenge of acute mesenteric ischemia. Visc Med. 2018;34(3):217-223. https://doi.org/10.1159/000490318
  • [14] Miller MA, Zachary JF. Mechanisms and morphology of cellular injury, adaptation, and death. Pathologic Basis of Veterinary Disease. 2017;2-43.e19. https://doi.org/10.1016/B978-0-323-35775-3.00001-1
  • [15] Castillo RL, González-Candia A, Carrasco R. Editorial: Mechanisms of ischemia-reperfusion injury in animal models and clinical conditions: Current concepts of pharmacological strategies. Front Physiol. 2022;13:880543. https://doi.org/10.3389/fphys.2022.880543
  • [16] Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011;17(11):1391-1401. https://doi.org/10.1038/nm.2507
  • [17] Tang SP, Mao XL, Chen YH, Yan LL, Ye LP, Li SW. Reactive oxygen species induce fatty liver and ischemia-reperfusion injury by promoting inflammation and cell death. Front Immunol. 2022;13:870239. https://doi.org/10.3389/fimmu.2022.870239
  • [18] Zhao T, Wu W, Sui L, Huang Q, Nan Yayun, Liu J, Ai K. Reactive oxygen species-based nanomaterials for the treatment of myocardial ischemia reperfusion injuries. Bioact Mater. 2021;7:47-72. https://doi.org/10.1016/j.bioactmat.2021.06.006
  • [19] Gottlieb RA. Cell death pathways in acute ischemia/reperfusion injury. J Cardiovasc Pharmacol Ther. 2011;16(3-4):233-238. https://doi.org/10.1177/1074248411409581
  • [20] Sung SJ, Fu SM. Interactions among glomerulus infiltrating macrophages and intrinsic cells via cytokines in chronic lupus glomerulonephritis. J Autoimmun. 2020;106:102331. https://doi.org/10.1016/j.jaut.2019.102331
  • [21] Akyüz C, Uzun O, Sunamak O, Velioğlu-Öğünç A, Çetinel Ş, Özer Şehirli A. The protective effect of spironolactone and role of the Na+/K+-ATPase pump on intestinal ischemia/reperfusion injury. Marmara Pharm J. 2018; 22(3): 429-435. https://doi.org/10.12991/jrp.2018.83
  • [22] Kim JS, Jeong K, Murphy JM, Rodriguez YAR, Lim SS. A Quantitative method to measure low levels of ROS in nonphagocytic cells by using a chemiluminescent imaging system. Oxid Med Cell Longev. 2019;2019:1754593. https://doi.org/10.1155/2019/1754593
  • [23] Wang R, Yue N, Fan A. Nanomaterial-enhanced chemiluminescence reactions and their applications. Analyst. 2020;145(23):7488-7510. https://doi.org/10.1039/d0an01300e
  • [24] Atalay S, Soylu B, Aykaç A, Velioğlu Öğünç A, Çetinel Ş, Özkan N, Erzik C, Şehirli AÖ. Protective effects of spironolactone against hepatic ischemia/reperfusion injury in rats. Turk J Surg. 2019;35(4):285-292. https://doi.org/10.5578/turkjsurg.4340
  • [25] Nauseef WM. Detection of superoxide anion and hydrogen peroxide production by cellular NADPH oxidases. Biochim Biophys Acta. 2014;1840(2):757-767. https://doi.org/10.1016/j.bbagen.2013.04.040
  • [26] Dirnagl U, Lindauer U, Them A, Schreiber S, Pfister HW, Koedel U, Reszka R, Freyer D, Villringer A. Global cerebral ischemia in the rat: online monitoring of oxygen free radical production using chemiluminescence in vivo. J Cereb Blood Flow Metab. 1995;15(6):929-940. https://doi.org/10.1038/jcbfm.1995.118
  • [27] Wang J. Neutrophils in tissue injury and repair. Cell Tissue Res. 2018;371(3):531-539. https://doi.org/10.1007/s00441-017-2785-7
  • [28] Su LJ, Zhang JH, Gomez H, Murugan R, Hong X, Xu D, Jiang F, Peng ZY. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev. 2019;2019:5080843. https://doi.org/10.1155/2019/5080843
  • [29] Ardid-Ruiz A, Harazin A, Barna L, Walter FR, Bladé C, Suárez M, Deli MA, Aragones G. The effects of Vitis vinifera L. phenolic compounds on a blood-brain barrier culture model: Expression of leptin receptors and protection against cytokine-induced damage. J Ethnopharmacol. 2020;247:112253. https://doi.org/10.1016/j.jep.2019.112253
  • [30] Dong W, Li F, Pan Z, Liu S, Yu H, Wang X, Bi S, Zhang W. Resveratrol ameliorates subacute intestinal ischemia-reperfusion injury. J Surg Res. 2013;185(1):182-189. https://doi.org/10.1016/j.jss.2013.05.013
  • [31] Yuluğ E, Türedi S, Karagüzel E, Kutlu O, Menteşe A, Alver A. The short term effects of resveratrol on ischemia-reperfusion injury in rat testis. J Pediatr Surg. 2014;49(3):484-489. https://doi.org/10.1016/j.jpedsurg.2013.08.028
  • [32] Fine AM. Oligomeric proanthocyanidin complexes: history, structure, and phytopharmaceutical applications. Altern Med Rev. 2000;5(2):144-151.
  • [33] Cádiz-Gurrea ML, Borrás-Linares I, Lozano-Sánchez J, Joven J, Fernández-Arroyo S, Segura-Carretero A. Cocoa and grape seed byproducts as a source of antioxidant and anti-inflammatory proanthocyanidins. Int J Mol Sci. 2017;18(2):376. https://doi.org/10.3390/ijms18020376
  • [34] Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351-358. https://doi.org/10.1016/0003-2697(79)90738-3
  • [35] Aykaç G, Uysal M, Yalçin AS, Koçak-Toker N, Sivas A, Oz H. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology. 1985;36(1):71-76. https://doi.org/10.1016/0300-483x(85)90008-3
  • [36] Hillegass LM, Griswold DE, Brickson B, Albrightson-Winslow C. Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods. 1990;24(4):285-295. https://doi.org/10.1016/0160-5402(90)90013-b
  • [37] Sastry GM, Adzhigirey M, Day T, Annabhimoju R, Sherman W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des. 2013;27(3):221-234. https://doi.org/10.1007/s10822-013-9644-8
  • [38] Kerstjens A, De Winter H. LEADD: Lamarckian evolutionary algorithm for de novo drug design. J Cheminform. 2022;14(1):3. https://doi.org/10.1186/s13321-022-00582-y
There are 38 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Chemistry
Journal Section Research Article
Authors

Cebrail Akyüz 0000-0003-0917-9345

Emine Erdağ

Ayliz Velioglu-ogunc This is me 0000-0001-8453-6491

Nurettin Abacioglu This is me 0000-0001-6609-1505

Ahmet Ozer Sehirli This is me

Publication Date June 28, 2025
Published in Issue Year 2023 Volume: 27 Issue: 4

Cite

APA Akyüz, C., Erdağ, E., Velioglu-ogunc, A., … Abacioglu, N. (2025). The protective effect of grape seed extract (Vitis vinifera) against mesenteric ischemia/reperfusion injury in rats: an in vivo, in vitro and molecular docking study. Journal of Research in Pharmacy, 27(4), 1513-1523.
AMA Akyüz C, Erdağ E, Velioglu-ogunc A, Abacioglu N, Sehirli AO. The protective effect of grape seed extract (Vitis vinifera) against mesenteric ischemia/reperfusion injury in rats: an in vivo, in vitro and molecular docking study. J. Res. Pharm. July 2025;27(4):1513-1523.
Chicago Akyüz, Cebrail, Emine Erdağ, Ayliz Velioglu-ogunc, Nurettin Abacioglu, and Ahmet Ozer Sehirli. “The Protective Effect of Grape Seed Extract (Vitis Vinifera) Against Mesenteric Ischemia Reperfusion Injury in Rats: An in Vivo, in Vitro and Molecular Docking Study”. Journal of Research in Pharmacy 27, no. 4 (July 2025): 1513-23.
EndNote Akyüz C, Erdağ E, Velioglu-ogunc A, Abacioglu N, Sehirli AO (July 1, 2025) The protective effect of grape seed extract (Vitis vinifera) against mesenteric ischemia/reperfusion injury in rats: an in vivo, in vitro and molecular docking study. Journal of Research in Pharmacy 27 4 1513–1523.
IEEE C. Akyüz, E. Erdağ, A. Velioglu-ogunc, N. Abacioglu, and A. O. Sehirli, “The protective effect of grape seed extract (Vitis vinifera) against mesenteric ischemia/reperfusion injury in rats: an in vivo, in vitro and molecular docking study”, J. Res. Pharm., vol. 27, no. 4, pp. 1513–1523, 2025.
ISNAD Akyüz, Cebrail et al. “The Protective Effect of Grape Seed Extract (Vitis Vinifera) Against Mesenteric Ischemia Reperfusion Injury in Rats: An in Vivo, in Vitro and Molecular Docking Study”. Journal of Research in Pharmacy 27/4 (July2025), 1513-1523.
JAMA Akyüz C, Erdağ E, Velioglu-ogunc A, Abacioglu N, Sehirli AO. The protective effect of grape seed extract (Vitis vinifera) against mesenteric ischemia/reperfusion injury in rats: an in vivo, in vitro and molecular docking study. J. Res. Pharm. 2025;27:1513–1523.
MLA Akyüz, Cebrail et al. “The Protective Effect of Grape Seed Extract (Vitis Vinifera) Against Mesenteric Ischemia Reperfusion Injury in Rats: An in Vivo, in Vitro and Molecular Docking Study”. Journal of Research in Pharmacy, vol. 27, no. 4, 2025, pp. 1513-2.
Vancouver Akyüz C, Erdağ E, Velioglu-ogunc A, Abacioglu N, Sehirli AO. The protective effect of grape seed extract (Vitis vinifera) against mesenteric ischemia/reperfusion injury in rats: an in vivo, in vitro and molecular docking study. J. Res. Pharm. 2025;27(4):1513-2.