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INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS

Year 2023, Volume: 24 Issue: 1, 11 - 20, 15.04.2023
https://doi.org/10.23902/trkjnat.1145462

Abstract

Pomegranate peel contains bioactive ingredients such as flavonoids, ellagitannins, phenolics and proanthocyanidin compounds with high antioxidant activity. Pomegranate peel has antiapoptotic, antioxidant and anti-inflammatory effects due to its high punicalagin content. We aimed to determine the effect of pomegranate peel extract (PPE) on lipopolysaccharide (LPS)-induced uveitis. Sixty rats were seperated randomly into twelve groups (n = 5). The healthy group received intraperitoneal normal saline, the uveitis group received 200 μg/kg LPS, the dexamethasone (DEX) group received 200 μg/kg LPS plus 1 mg/kg DEX, the PPE100, PPE300 and PPE500 groups received 200 μg/kg LPS plus 100, 300 and 500 mg/kg PPE, respectively. The eye tissues were collected at 3rd and 24th hour. and investigated molecularly (Relative quantification of gene expression), biochemically (Superoxide dismutase activity, Glutathione and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Tumor Necrosis Factor-α, vascular endothelial growth factor, and Caspase-3 levels markedly decreased in a dose-dependent manner in the uveitic rats following PPE administration. PPE administration significantly ameliorated uveitic disorders in oxidative stress factors including Glutathione, Superoxide dismutase and Malondialdehyde, with its effects raising in a dose-dependent manner. PPE eliminated histopathological changes in eye tissues due to uveitis. PPE can be a promising agent by contributing to alternative preventive treatment methods for uveitis with its anti-inflammatory, antioxidative, antiapoptotic and antiangiogenic effects.

Supporting Institution

the Scientific Research Council of Tekirdağ Namık Kemal University

Project Number

NKUBAP.02.GA.20.240

Thanks

Part of this study was presented orally at the 5th International Hippocrates Congress on Medical and Health Sciences on 18-19 December 2020.

References

  • 1. Ai, X., Hou, Y., Wang, X., Wang, X., Liang, Y., Zhu, Z., Wang, P., Zeng, Y., Li, X., Lai, X., Meng, X. & Li, Q. 2019. Amelioration of dry eye syndrome in db/db mice with diabetes mellitus by treatment with Tibetan Medicine Formula Jikan Mingmu Drops. Journal of Ethnopharmacology, 241: 111992. https://doi.org/10.1016/j.jep.2019.111992
  • 2. Akpinar, E., Kutlu, Z., Kose, D., Aydin, P., Tavaci, T., Bayraktutan, Z., Yuksel, T.N., Yildirim, S., Eser, G. & Dincer, B. 2022. Protective Effects of Idebenone against Sepsis Induced Acute Lung Damage. J Journal of Investigative Surgery, 35(3): 560-568. https://doi.org/10.1080/08941939.2021.1898063
  • 3. Alexandre, E.M.C., Silva, S., Santos, S.A.O., Silvestre, A.J.D., Duarte, M.F., Saraiva, J.A. & Pintado, M. 2019. Antimicrobial activity of pomegranate peel extracts performed by high pressure and enzymatic assisted extraction. Food Research International 115: 167-176. https://doi.org/10.1016/j.foodres.2018.08.044
  • 4. Amer, O.S., Dkhil, M.A., Hikal, W.M. & Al-Quraishy, S. 2015. Antioxidant and anti-inflammatory activities of pomegranate (Punica granatum) on Eimeria papillata-induced infection in mice. Biomed Research International, 2015: 219670. https://doi.org/10.1155/2015/219670
  • 5. Bagheri, S., Khorramabadi, R.M., Assadollahi, V., Khosravi, P., Cheraghi Venol, A., Veiskerami, S. & Ahmadvand, H. 2021. The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes. Archives of Physiology and Biochemistry 1-9. https://doi.org/10.1080/13813455.2021.1877308
  • 6. 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 Medicine and Therapies, 17(1): 47. https://doi.org/10.1186/s12906-017-1555-0
  • 7. Chang, Y.H., Horng, C.T., Chen, Y.H., Chen, P.L., Chen, C.L., Liang, C.M., Chien, M.W. & Chen, J.T. 2008. Inhibitory effects of glucosamine on endotoxin-induced uveitis in Lewis rats. Investigative Ophthalmology & Visual Science, 49(12): 5441-5449. https://doi.org/10.1167/iovs.08-1784
  • 8. Chang, Y.S., Lin, C.F., Wu, C.L., Kuo, P.Y., Wu, F.S., Shieh, C.C., Gean, P.W., Chen, S.T., Chen, M.S., Wu, W.C., Tai, M.H. & Tseng, S.H. 2011. Mechanisms underlying benzyl alcohol cytotoxicity (triamcinolone acetonide preservative) in human retinal pigment epithelial cells. Investigative Ophthalmology & Visual Science, 52(7): 4214-4222. https://doi.org/10.1167/iovs.10-6058
  • 9. Cinar, I., Sirin, B., Aydin, P., Toktay, E., Cadirci, E., Halici, I. & Halici, Z. 2019. Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats. Life Sciences, 221: 327-334. https://doi.org/10.1016/j.lfs.2019.02.039
  • 10. Classics Lowry, O., Rosebrough, N., Farr, A., & Randall, R. 1951. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193(1): 265-75.
  • 11. Crabtree, E., Uribe, K., Smith, S.M., Roberts, D., Salmon, J.H., Bower, J.J., Song, L., Bastola, P., Hirsch, M.L. & Gilger, B.C. 2022. Inhibition of experimental autoimmune uveitis by intravitreal AAV-Equine-IL10 gene therapy. PLoS One, 17(8): e0270972. https://doi.org/10.1371/journal.pone.0270972
  • 12. Curnow, S.J. & Murray, P.I. 2006. Inflammatory mediators of uveitis: cytokines and chemokines. Current Opinion in Ophthalmology, 17(6): 532-537. https://doi.org/10.1097/ICU.0b013e32801094b5
  • 13. Dana, N., Javanmard Sh, H. & Rafiee, L. 2015. Antiangiogenic and antiproliferative effects of black pomegranate peel extract on melanoma cell line. Research in Pharmaceutical Sciences, 10(2): 117-124.
  • 14. Dick, A.D., Forrester, J.V., Liversidge, J. & Cope, A.P. 2004. The role of tumour necrosis factor (TNF-α) in experimental autoimmune uveoretinitis (EAU). Progress in Retinal and Eye Research, 23(6): 617-637.
  • 15. Do, J.Y., Choi, Y.K., Kook, H., Suk, K., Lee, I.K. & Park, D.H. 2015. Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor gamma. Biochemical and Biophysical Research Communications, 460(2): 457-463. https://doi.org/10.1016/j.bbrc.2015.03.055
  • 16. Doostan, F., Vafafar, R., Zakeri-Milani, P., Pouri, A., Amini Afshar, R. & Mesgari Abbasi, M. 2017. Effects of Pomegranate (Punica Granatum L.) Seed and Peel Methanolic Extracts on Oxidative Stress and Lipid Profile Changes Induced by Methotrexate in Rats. Advanced Pharmaceutical Bulletin, 7(2): 269-274. https://doi.org/10.15171/apb.2017.032
  • 17. El-Bouhy, Z.M., Reda, R.M., Mahboub, H.H. & Gomaa, F.N. 2021. Bioremediation effect of pomegranate peel on subchronic mercury immunotoxicity on African catfish (Clarias gariepinus). Environmental Science and Pollution Research, 28(2): 2219-2235. https://doi.org/10.1007/s11356-020-10599-1
  • 18. El Bohi, K.M., Abdel-Motal, S.M., Khalil, S.R., Abd-Elaal, M.M., Metwally, M.M.M. & WM, E.L. 2021. The efficiency of pomegranate (Punica granatum) peel ethanolic extract in attenuating the vancomycin-triggered liver and kidney tissues injury in rats. Environmental Science and Pollution Research, 28(6): 7134-7150. https://doi.org/10.1007/s11356-020-10999-3
  • 19. Elwej, A., Ghorbel, I., Marrekchi, R., Boudawara, O., Jamoussi, K., Boudawara, T., Zeghal, N. & Sefi, M. 2016. Improvement of kidney redox states contributes to the beneficial effects of dietary pomegranate peel against barium chloride-induced nephrotoxicity in adult rats. Archives of Physiology and Biochemistry, 122(3): 130-140. https://doi.org/10.3109/13813455.2016.1150298
  • 20. Emam, N.M., Anjum, S., Okail, H.A., Ibrahim, M.A.R. & Ahmad, T. 2020. Pomegranate peel extract protects against carbon tetrachloride-induced nephrotoxicity in mice through increasing antioxidants status. Biomedical Reports, 13(3): 13. https://doi.org/10.3892/br.2020.1320
  • 21. Famiglietti, E.V., Stopa, E.G., McGookin, E.D., Song, P., LeBlanc, V. & Streeten, B.W. 2003. Immunocytochemical localization of vascular endothelial growth factor in neurons and glial cells of human retina. Brain Research, 969(1-2): 195-204. https://doi.org/10.1016/s0006-8993(02)03766-6
  • 22. Garcia-Otero, X., Mondelo-Garcia, C., Gonzalez, F., Perez-Fernandez, R., Avila, L., Antunez-Lopez, J.R., Gonzalez-Barcia, M., Adan, A., Aguiar, P., Otero-Espinar, F.J., Bermudez, M.A. & Fernandez-Ferreiro, A. 2021. Anti-Inflammatory Effect of Tacrolimus/Hydroxypropyl-beta-Cyclodextrin Eye Drops in an Endotoxin-Induced Uveitis Model. Pharmaceutics, 13(10). https://doi.org/10.3390/pharmaceutics13101737
  • 23. Gil, M.I., Tomas-Barberan, F.A., Hess-Pierce, B., Holcroft, D.M. & Kader, A.A. 2000. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. Journal of Agricultural and Food Chemistry, 48(10): 4581-4589. https://doi.org/10.1021/jf000404a
  • 24. Guly, C.M. & Forrester, J.V. 2010. Investigation and management of uveitis. British Medical Journal, 341: c4976. https://doi.org/10.1136/bmj.c4976
  • 25. Hashem, H.E., Abd El-Haleem, M.R., Amer, M.G. & Bor'i, A. 2017. Pomegranate protective effect on experimental ischemia/reperfusion retinal injury in rats (histological and biochemical study). Ultrastructural Pathology,41(5): 346-357. https://doi.org/10.1080/01913123.2017.1346737
  • 26. Kaur, M., Velmurugan, B., Rajamanickam, S., Agarwal, R. & Agarwal, C. 2009. Gallic acid, an active constituent of grape seed extract, exhibits anti-proliferative, pro-apoptotic and anti-tumorigenic effects against prostate carcinoma xenograft growth in nude mice. Pharmaceutical Research, 26(9): 2133-2140. https://doi.org/10.1007/s11095-009-9926-y
  • 27. Keles, S., Halici, Z., Atmaca, H.T., Yayla, M., Yildirim, K., Ekinci, M., Akpinar, E., Altuner, D., Cakici, O. & Bayraktutan, Z. 2014. The ocular endothelin system: a novel target for the treatment of endotoxin-induced uveitis with bosentan. Investigative Ophthalmology & Visual Science, 55(6): 3517-3524. https://doi.org/10.1167/iovs.14-14193
  • 28. Khan, S.A., Shahid, S., Mahmood, T. & Lee, C.S. 2021. Contact lenses coated with hybrid multifunctional ternary nanocoatings (Phytomolecule-coated ZnO nanoparticles:Gallic Acid:Tobramycin) for the treatment of bacterial and fungal keratitis. Acta Biomaterialia, 128: 262-276. https://doi.org/10.1016/j.actbio.2021.04.014
  • 29. Kim, E.Y. & Moudgil, K.D. 2008. Regulation of autoimmune inflammation by pro-inflammatory cytokines. Immunology Letters, 120(1-2): 1-5. https://doi.org/10.1016/j.imlet.2008.07.008
  • 30. Konsoula, Z. 2016. Comparative efficacy of pomegranate juice, peel and seed extract in the stabilization of corn oil under accelerated conditions. International Journal of Nutrition and Food Engineering, 10(9): 556-563.
  • 31. Kutlu, Z., Celik, M., Bilen, A., Halici, Z., Yildirim, S., Karabulut, S., Karakaya, S., Bostanlik, D.F. & Aydin, P. 2020. Effects of umbelliferone isolated from the Ferulago pauciradiata Boiss. & Heldr. Plant on cecal ligation and puncture-induced sepsis model in rats. Biomedicine & Pharmacotherapy, 127: 110206. https://doi.org/10.1016/j.biopha.2020.110206
  • 32. Labsi, M., Soufli, I., Belguendouz, H., Djebbara, S., Hannachi, L., Amir, Z.C. & Touil-Boukoffa, C. 2021. Beneficial effect of dimethyl fumarate on experimental autoimmune uveitis is dependent of pro-inflammatory markers immunomodulation. Inflammopharmacology, 29(5): 1389-1398. https://doi.org/10.1007/s10787-021-00864-1
  • 33. LeHoang, P. 2012. The gold standard of noninfectious uveitis: corticosteroids. Developments in Ophthalmology, 51: 7-28. https://doi.org/10.1159/000336676
  • 34. Les, F., Prieto, J.M., Arbones-Mainar, J.M., Valero, M.S. & Lopez, V. 2015. Bioactive properties of commercialised pomegranate (Punica granatum) juice: antioxidant, antiproliferative and enzyme inhibiting activities. Food & Function, 6(6): 2049-2057. https://doi.org/10.1039/c5fo00426h
  • 35. Lin, H., Wang, Q., Niu, Y., Gu, L., Hu, L., Li, C. & Zhao, G. 2021. Antifungal and Anti-inflammatory Effect of Punicalagin on Murine Aspergillus fumigatus Keratitis. Current Eye Research: 1-8. https://doi.org/10.1080/02713683.2021.2008982
  • 36. Mastrogiovanni, F., Bernini, R., Basirico, L., Bernabucci, U., Campo, M., Romani, A., Santi, L. & Lacetera, N. 2020. Antioxidant and anti-inflammatory effects of pomegranate peel extracts on bovine mammary epithelial cells BME-UV1. Natural Product Research, 34(10): 1465-1469. https://doi.org/10.1080/14786419.2018.1508149
  • 37. Park, S., Seok, J.K., Kwak, J.Y., Suh, H.J., Kim, Y.M. & Boo, Y.C. 2016. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10. Evidence-based Complementary Alternative Medicine, 2016: 6836080. https://doi.org/10.1155/2016/6836080
  • 38. Kamboh, A.A. 2016. Effect of Pomegranate Peel Extract on some Biochemical and Histopathological Parameters in Experimental Induced Mice with Staphylococcus aureus. Journal of Animal Health and Production, 4(2): 42-49.
  • 39. Read, R.W. 2006. Uveitis: advances in understanding of pathogenesis and treatment. Current Rheumatology Reports, 8(4): 260-266. https://doi.org/10.1007/s11926-006-0006-6
  • 40. Rosenbaum, J.T., McDevitt, H.O., Guss, R.B. & Egbert, P.R. 1980. Endotoxin-induced uveitis in rats as a model for human disease. Nature, 286(5773): 611-613. https://doi.org/10.1038/286611a0
  • 41. Ugan, R.A., Yayla, M., Un, H., Civelek, M.S. & Aksu Kilicle, P. 2020. Nar Kabuğu Ekstresinin Sıçanlarda Diyabetik Şartlarda Sepsis ile İndüklenen Akciğer Hasarına Karşı Etkileri. Dicle Medical Journal, 47(3): 678-686.
  • 42. Sadeghipour, A., Eidi, M., Ilchizadeh Kavgani, A., Ghahramani, R., Shahabzadeh, S. & Anissian, A. 2014. Lipid Lowering Effect of Punica granatum L. Peel in High Lipid Diet Fed Male Rats. Evid Evidence Based Complementary and Alternative Medicine, 2014: 432650. https://doi.org/10.1155/2014/432650
  • 43. Scholz, R., Sobotka, M., Caramoy, A., Stempfl, T., Moehle, C. & Langmann, T. 2015. Minocycline counter-regulates pro-inflammatory microglia responses in the retina and protects from degeneration. Journal of Neuroinflammation, 12: 209. https://doi.org/10.1186/s12974-015-0431-4
  • 44. Seve, P., Cacoub, P., Bodaghi, B., Trad, S., Sellam, J., Bellocq, D., Bielefeld, P., Sene, D., Kaplanski, G., Monnet, D., Brezin, A., Weber, M., Saadoun, D., Chiquet, C. & Kodjikian, L. 2017. Uveitis: Diagnostic work-up. A literature review and recommendations from an expert committee. Autoimmunity Reviews, 16(12): 1254-1264. https://doi.org/10.1016/j.autrev.2017.10.010
  • 45. Stoddard, A.R., Koetje, L.R., Mitchell, A.K., Schotanus, M.P. & Ubels, J.L. 2013. Bioavailability of antioxidants applied to stratified human corneal epithelial cells. Journal of Ocular Pharmacology and Therapeutics, 29(7): 681-687. https://doi.org/10.1089/jop.2013.0014
  • 46. Sugita, S., Takase, H., Taguchi, C. & Mochizuki, M. 2007. The role of soluble TNF receptors for TNF-alpha in uveitis. Investigative Ophthalmology & Visual Science, 48(7): 3246-3252. https://doi.org/10.1167/iovs.06-1444
  • 47. Suttorp-Schulten, M.S. & Rothova, A. 1996. The possible impact of uveitis in blindness: a literature survey. BMJ Open Ophthalmology, 80(9): 844-848. https://doi.org/10.1136/bjo.80.9.844
  • 48. Tagirasa, R., Parmar, S., Barik, M.R., Devadas, S. & Basu, S. 2017. Autoreactive T Cells in Immunopathogenesis of TB-Associated Uveitis. Investigative Ophthalmology & Visual Science, 58(13): 5682-5691. https://doi.org/10.1167/iovs.17-22462
  • 49. Ugan, R.A. & Un, H. 2020. The Protective Roles of Butein on Indomethacin Induced Gastric Ulcer in Mice. The Eurasian Journal of Medicine, 52(3): 265-270. https://doi.org/10.5152/eurasianjmed.2020.20022
  • 50. Un, H., Ugan, R.A., Kose, D., Yayla, M., Tastan, T.B., Bayir, Y. & Halici, Z. 2022. A new approach to sepsis treatment by rasagiline: a molecular, biochemical and histopathological study. Molecular Biology Reports, 49: 3875-3883. https://doi.org/10.1007/s11033-022-07235-1
  • 51. Wang, L. & Weller, C.L. 2006. Recent advances in extraction of nutraceuticals from plants. Trends in Food Science & Technology, 17(6): 300-312.
  • 52. Wang, T., Men, R., Hu, M., Fan, X., Yang, X., Huang, X., Ye, T. & Yang, L. 2018. Protective effects of Punica granatum (pomegranate) peel extract on concanavalin A-induced autoimmune hepatitis in mice. Biomedicine & Pharmacotherapy, 100: 213-220. https://doi.org/10.1016/j.biopha.2017.12.110
  • 53. Xu, J., Guo, C.J., Yang, J.J., Wei, J.Y., Li, Y.F., Pang, W., Jiang, Y.G. & Cheng, S. 2005. Intervention of antioxidant system function of aged rats by giving fruit juices with different antioxidant capacities. Zhonghua Yu Fang Yi Xue Za Zhi, 39(2): 80-83.
  • 54. Xu, X., Li, H., Hou, X., Li, D., He, S., Wan, C., Yin, P., Liu, M., Liu, F. & Xu, J. 2015. Punicalagin Induces Nrf2/HO-1 Expression via Upregulation of PI3K/AKT Pathway and Inhibits LPS-Induced Oxidative Stress in RAW264.7 Macrophages. Mediators of Inflammation, 2015: 380218. https://doi.org/10.1155/2015/380218
  • 55. Yadav, U.C., Kalariya, N.M. & Ramana, K.V. 2011. Emerging role of antioxidants in the protection of uveitis complications. Current Medicinal Chemistry, 18(6): 931-942. https://doi.org/10.2174/092986711794927694
  • 56. Yadav, U.C., Subramanyam, S. & Ramana, K.V. 2009. Prevention of endotoxin-induced uveitis in rats by benfotiamine, a lipophilic analogue of vitamin B1. Investigative Ophthalmology & Visual Science, 50(5): 2276-2282. https://doi.org/10.1167/iovs.08-2816
  • 57. Yaidikar, L., Byna, B. & Thakur, S.R. 2014. Neuroprotective effect of punicalagin against cerebral ischemia reperfusion-induced oxidative brain injury in rats. Journal of Stroke and Cerebrovascular Diseases, 23(10): 2869-2878. https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.07.020
  • 58. Yayla, M., Cadirci, E., Halici, Z., Bakan, F., Ay, N., Demirci, S., Karaman, A. & Sahin, F. 2020. Regenerative Effect of Resorbable Scaffold Embedded Boron-Nitride/Hydroxyapatite Nanoparticles in Rat Parietal Bone. Journal of Nanoscience and Nanotechnology, 20(2): 680-691. https://doi.org/10.1166/jnn.2020.17128
  • 59. Yoshida, Y., Yamagishi, S., Matsui, T., Jinnouchi, Y., Fukami, K., Imaizumi, T. & Yamakawa, R. 2009. Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathy. Diabetes/Metabolism Research and Reviews, 25(7): 678-686. https://doi.org/10.1002/dmrr.1007
  • 60. Zhang, N., Yu, S., Liu, X. & Lu, H. 2017. Low Dose of Lipopolysaccharide Pretreatment Preventing Subsequent Endotoxin-Induced Uveitis Is Associated with PI3K/AKT Pathway. Journal of Immunology Research, 2017: 1273940. https://doi.org/10.1155/2017/1273940
Year 2023, Volume: 24 Issue: 1, 11 - 20, 15.04.2023
https://doi.org/10.23902/trkjnat.1145462

Abstract

Nar kabuğu, yüksek antioksidan aktiviteye sahip flavonoitler, elajitanenler, fenolikler ve proantosiyanidin bileşikleri gibi biyoaktif bileşenler içermesi nedeniyle en faydalı parçalardan biridir. Nar kabuğundaki yüksek punikalagin içeriği, antienflamatuvar, antioksidan ve antiapoptotik etkiler üretmesini sağlar. Bu çalışmada deneysel lipopolisakkarit (LPS) kaynaklı üveit modelinde nar kabuğu ekstresinin (NKE) koruyucu etkilerini değerlendirmeyi amaçladık. 60 sıçan rastgele 12 gruba ayrıldı (n = 5). Sağlıklı grup intraperitoneal normal salin; üveit grubu 200 μg/kg LPS; deksametazon (DEX) grubu 200 μg/kg LPS ve 1 mg/kg DEX; NKE100, NKE300 ve NKE500 grupları ise 200 μg/kg LPS ile birlikte sırasıyla 100, 300 ve 500 mg/kg NKE aldı. Göz dokuları 3. ve 24. saatte toplandı ve moleküler, biyokimyasal ve histopatolojik olarak incelendi. NKE uygulamasını takiben üveitik sıçanlarda tümör nekroz faktörü-α, vasküler endotelyal büyüme faktörü ve kaspaz-3 seviyeleri doza bağlı olarak belirgin şekilde azaldı. NKE uygulaması, doza bağlı olarak artan etkileri ile Glutatyon, Süperoksit dismutaz ve Malondialdehit gibi oksidatif strese bağlı faktörlerdeki üveitik bozuklukları önemli ölçüde iyileştirdi. NKE ayrıca üveit ile ilişkili göz dokularındaki histopatolojik değişiklikleri de ortadan kaldırdı. NKE, antienflamatuvar, antioksidan, antiapoptotik ve antianjiyojenik etkileri ile üveit için alternatif koruyucu tedavi yöntemlerine katkıda bulunarak umut verici bir ajan olabilir.

Project Number

NKUBAP.02.GA.20.240

References

  • 1. Ai, X., Hou, Y., Wang, X., Wang, X., Liang, Y., Zhu, Z., Wang, P., Zeng, Y., Li, X., Lai, X., Meng, X. & Li, Q. 2019. Amelioration of dry eye syndrome in db/db mice with diabetes mellitus by treatment with Tibetan Medicine Formula Jikan Mingmu Drops. Journal of Ethnopharmacology, 241: 111992. https://doi.org/10.1016/j.jep.2019.111992
  • 2. Akpinar, E., Kutlu, Z., Kose, D., Aydin, P., Tavaci, T., Bayraktutan, Z., Yuksel, T.N., Yildirim, S., Eser, G. & Dincer, B. 2022. Protective Effects of Idebenone against Sepsis Induced Acute Lung Damage. J Journal of Investigative Surgery, 35(3): 560-568. https://doi.org/10.1080/08941939.2021.1898063
  • 3. Alexandre, E.M.C., Silva, S., Santos, S.A.O., Silvestre, A.J.D., Duarte, M.F., Saraiva, J.A. & Pintado, M. 2019. Antimicrobial activity of pomegranate peel extracts performed by high pressure and enzymatic assisted extraction. Food Research International 115: 167-176. https://doi.org/10.1016/j.foodres.2018.08.044
  • 4. Amer, O.S., Dkhil, M.A., Hikal, W.M. & Al-Quraishy, S. 2015. Antioxidant and anti-inflammatory activities of pomegranate (Punica granatum) on Eimeria papillata-induced infection in mice. Biomed Research International, 2015: 219670. https://doi.org/10.1155/2015/219670
  • 5. Bagheri, S., Khorramabadi, R.M., Assadollahi, V., Khosravi, P., Cheraghi Venol, A., Veiskerami, S. & Ahmadvand, H. 2021. The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes. Archives of Physiology and Biochemistry 1-9. https://doi.org/10.1080/13813455.2021.1877308
  • 6. 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 Medicine and Therapies, 17(1): 47. https://doi.org/10.1186/s12906-017-1555-0
  • 7. Chang, Y.H., Horng, C.T., Chen, Y.H., Chen, P.L., Chen, C.L., Liang, C.M., Chien, M.W. & Chen, J.T. 2008. Inhibitory effects of glucosamine on endotoxin-induced uveitis in Lewis rats. Investigative Ophthalmology & Visual Science, 49(12): 5441-5449. https://doi.org/10.1167/iovs.08-1784
  • 8. Chang, Y.S., Lin, C.F., Wu, C.L., Kuo, P.Y., Wu, F.S., Shieh, C.C., Gean, P.W., Chen, S.T., Chen, M.S., Wu, W.C., Tai, M.H. & Tseng, S.H. 2011. Mechanisms underlying benzyl alcohol cytotoxicity (triamcinolone acetonide preservative) in human retinal pigment epithelial cells. Investigative Ophthalmology & Visual Science, 52(7): 4214-4222. https://doi.org/10.1167/iovs.10-6058
  • 9. Cinar, I., Sirin, B., Aydin, P., Toktay, E., Cadirci, E., Halici, I. & Halici, Z. 2019. Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats. Life Sciences, 221: 327-334. https://doi.org/10.1016/j.lfs.2019.02.039
  • 10. Classics Lowry, O., Rosebrough, N., Farr, A., & Randall, R. 1951. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193(1): 265-75.
  • 11. Crabtree, E., Uribe, K., Smith, S.M., Roberts, D., Salmon, J.H., Bower, J.J., Song, L., Bastola, P., Hirsch, M.L. & Gilger, B.C. 2022. Inhibition of experimental autoimmune uveitis by intravitreal AAV-Equine-IL10 gene therapy. PLoS One, 17(8): e0270972. https://doi.org/10.1371/journal.pone.0270972
  • 12. Curnow, S.J. & Murray, P.I. 2006. Inflammatory mediators of uveitis: cytokines and chemokines. Current Opinion in Ophthalmology, 17(6): 532-537. https://doi.org/10.1097/ICU.0b013e32801094b5
  • 13. Dana, N., Javanmard Sh, H. & Rafiee, L. 2015. Antiangiogenic and antiproliferative effects of black pomegranate peel extract on melanoma cell line. Research in Pharmaceutical Sciences, 10(2): 117-124.
  • 14. Dick, A.D., Forrester, J.V., Liversidge, J. & Cope, A.P. 2004. The role of tumour necrosis factor (TNF-α) in experimental autoimmune uveoretinitis (EAU). Progress in Retinal and Eye Research, 23(6): 617-637.
  • 15. Do, J.Y., Choi, Y.K., Kook, H., Suk, K., Lee, I.K. & Park, D.H. 2015. Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor gamma. Biochemical and Biophysical Research Communications, 460(2): 457-463. https://doi.org/10.1016/j.bbrc.2015.03.055
  • 16. Doostan, F., Vafafar, R., Zakeri-Milani, P., Pouri, A., Amini Afshar, R. & Mesgari Abbasi, M. 2017. Effects of Pomegranate (Punica Granatum L.) Seed and Peel Methanolic Extracts on Oxidative Stress and Lipid Profile Changes Induced by Methotrexate in Rats. Advanced Pharmaceutical Bulletin, 7(2): 269-274. https://doi.org/10.15171/apb.2017.032
  • 17. El-Bouhy, Z.M., Reda, R.M., Mahboub, H.H. & Gomaa, F.N. 2021. Bioremediation effect of pomegranate peel on subchronic mercury immunotoxicity on African catfish (Clarias gariepinus). Environmental Science and Pollution Research, 28(2): 2219-2235. https://doi.org/10.1007/s11356-020-10599-1
  • 18. El Bohi, K.M., Abdel-Motal, S.M., Khalil, S.R., Abd-Elaal, M.M., Metwally, M.M.M. & WM, E.L. 2021. The efficiency of pomegranate (Punica granatum) peel ethanolic extract in attenuating the vancomycin-triggered liver and kidney tissues injury in rats. Environmental Science and Pollution Research, 28(6): 7134-7150. https://doi.org/10.1007/s11356-020-10999-3
  • 19. Elwej, A., Ghorbel, I., Marrekchi, R., Boudawara, O., Jamoussi, K., Boudawara, T., Zeghal, N. & Sefi, M. 2016. Improvement of kidney redox states contributes to the beneficial effects of dietary pomegranate peel against barium chloride-induced nephrotoxicity in adult rats. Archives of Physiology and Biochemistry, 122(3): 130-140. https://doi.org/10.3109/13813455.2016.1150298
  • 20. Emam, N.M., Anjum, S., Okail, H.A., Ibrahim, M.A.R. & Ahmad, T. 2020. Pomegranate peel extract protects against carbon tetrachloride-induced nephrotoxicity in mice through increasing antioxidants status. Biomedical Reports, 13(3): 13. https://doi.org/10.3892/br.2020.1320
  • 21. Famiglietti, E.V., Stopa, E.G., McGookin, E.D., Song, P., LeBlanc, V. & Streeten, B.W. 2003. Immunocytochemical localization of vascular endothelial growth factor in neurons and glial cells of human retina. Brain Research, 969(1-2): 195-204. https://doi.org/10.1016/s0006-8993(02)03766-6
  • 22. Garcia-Otero, X., Mondelo-Garcia, C., Gonzalez, F., Perez-Fernandez, R., Avila, L., Antunez-Lopez, J.R., Gonzalez-Barcia, M., Adan, A., Aguiar, P., Otero-Espinar, F.J., Bermudez, M.A. & Fernandez-Ferreiro, A. 2021. Anti-Inflammatory Effect of Tacrolimus/Hydroxypropyl-beta-Cyclodextrin Eye Drops in an Endotoxin-Induced Uveitis Model. Pharmaceutics, 13(10). https://doi.org/10.3390/pharmaceutics13101737
  • 23. Gil, M.I., Tomas-Barberan, F.A., Hess-Pierce, B., Holcroft, D.M. & Kader, A.A. 2000. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. Journal of Agricultural and Food Chemistry, 48(10): 4581-4589. https://doi.org/10.1021/jf000404a
  • 24. Guly, C.M. & Forrester, J.V. 2010. Investigation and management of uveitis. British Medical Journal, 341: c4976. https://doi.org/10.1136/bmj.c4976
  • 25. Hashem, H.E., Abd El-Haleem, M.R., Amer, M.G. & Bor'i, A. 2017. Pomegranate protective effect on experimental ischemia/reperfusion retinal injury in rats (histological and biochemical study). Ultrastructural Pathology,41(5): 346-357. https://doi.org/10.1080/01913123.2017.1346737
  • 26. Kaur, M., Velmurugan, B., Rajamanickam, S., Agarwal, R. & Agarwal, C. 2009. Gallic acid, an active constituent of grape seed extract, exhibits anti-proliferative, pro-apoptotic and anti-tumorigenic effects against prostate carcinoma xenograft growth in nude mice. Pharmaceutical Research, 26(9): 2133-2140. https://doi.org/10.1007/s11095-009-9926-y
  • 27. Keles, S., Halici, Z., Atmaca, H.T., Yayla, M., Yildirim, K., Ekinci, M., Akpinar, E., Altuner, D., Cakici, O. & Bayraktutan, Z. 2014. The ocular endothelin system: a novel target for the treatment of endotoxin-induced uveitis with bosentan. Investigative Ophthalmology & Visual Science, 55(6): 3517-3524. https://doi.org/10.1167/iovs.14-14193
  • 28. Khan, S.A., Shahid, S., Mahmood, T. & Lee, C.S. 2021. Contact lenses coated with hybrid multifunctional ternary nanocoatings (Phytomolecule-coated ZnO nanoparticles:Gallic Acid:Tobramycin) for the treatment of bacterial and fungal keratitis. Acta Biomaterialia, 128: 262-276. https://doi.org/10.1016/j.actbio.2021.04.014
  • 29. Kim, E.Y. & Moudgil, K.D. 2008. Regulation of autoimmune inflammation by pro-inflammatory cytokines. Immunology Letters, 120(1-2): 1-5. https://doi.org/10.1016/j.imlet.2008.07.008
  • 30. Konsoula, Z. 2016. Comparative efficacy of pomegranate juice, peel and seed extract in the stabilization of corn oil under accelerated conditions. International Journal of Nutrition and Food Engineering, 10(9): 556-563.
  • 31. Kutlu, Z., Celik, M., Bilen, A., Halici, Z., Yildirim, S., Karabulut, S., Karakaya, S., Bostanlik, D.F. & Aydin, P. 2020. Effects of umbelliferone isolated from the Ferulago pauciradiata Boiss. & Heldr. Plant on cecal ligation and puncture-induced sepsis model in rats. Biomedicine & Pharmacotherapy, 127: 110206. https://doi.org/10.1016/j.biopha.2020.110206
  • 32. Labsi, M., Soufli, I., Belguendouz, H., Djebbara, S., Hannachi, L., Amir, Z.C. & Touil-Boukoffa, C. 2021. Beneficial effect of dimethyl fumarate on experimental autoimmune uveitis is dependent of pro-inflammatory markers immunomodulation. Inflammopharmacology, 29(5): 1389-1398. https://doi.org/10.1007/s10787-021-00864-1
  • 33. LeHoang, P. 2012. The gold standard of noninfectious uveitis: corticosteroids. Developments in Ophthalmology, 51: 7-28. https://doi.org/10.1159/000336676
  • 34. Les, F., Prieto, J.M., Arbones-Mainar, J.M., Valero, M.S. & Lopez, V. 2015. Bioactive properties of commercialised pomegranate (Punica granatum) juice: antioxidant, antiproliferative and enzyme inhibiting activities. Food & Function, 6(6): 2049-2057. https://doi.org/10.1039/c5fo00426h
  • 35. Lin, H., Wang, Q., Niu, Y., Gu, L., Hu, L., Li, C. & Zhao, G. 2021. Antifungal and Anti-inflammatory Effect of Punicalagin on Murine Aspergillus fumigatus Keratitis. Current Eye Research: 1-8. https://doi.org/10.1080/02713683.2021.2008982
  • 36. Mastrogiovanni, F., Bernini, R., Basirico, L., Bernabucci, U., Campo, M., Romani, A., Santi, L. & Lacetera, N. 2020. Antioxidant and anti-inflammatory effects of pomegranate peel extracts on bovine mammary epithelial cells BME-UV1. Natural Product Research, 34(10): 1465-1469. https://doi.org/10.1080/14786419.2018.1508149
  • 37. Park, S., Seok, J.K., Kwak, J.Y., Suh, H.J., Kim, Y.M. & Boo, Y.C. 2016. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10. Evidence-based Complementary Alternative Medicine, 2016: 6836080. https://doi.org/10.1155/2016/6836080
  • 38. Kamboh, A.A. 2016. Effect of Pomegranate Peel Extract on some Biochemical and Histopathological Parameters in Experimental Induced Mice with Staphylococcus aureus. Journal of Animal Health and Production, 4(2): 42-49.
  • 39. Read, R.W. 2006. Uveitis: advances in understanding of pathogenesis and treatment. Current Rheumatology Reports, 8(4): 260-266. https://doi.org/10.1007/s11926-006-0006-6
  • 40. Rosenbaum, J.T., McDevitt, H.O., Guss, R.B. & Egbert, P.R. 1980. Endotoxin-induced uveitis in rats as a model for human disease. Nature, 286(5773): 611-613. https://doi.org/10.1038/286611a0
  • 41. Ugan, R.A., Yayla, M., Un, H., Civelek, M.S. & Aksu Kilicle, P. 2020. Nar Kabuğu Ekstresinin Sıçanlarda Diyabetik Şartlarda Sepsis ile İndüklenen Akciğer Hasarına Karşı Etkileri. Dicle Medical Journal, 47(3): 678-686.
  • 42. Sadeghipour, A., Eidi, M., Ilchizadeh Kavgani, A., Ghahramani, R., Shahabzadeh, S. & Anissian, A. 2014. Lipid Lowering Effect of Punica granatum L. Peel in High Lipid Diet Fed Male Rats. Evid Evidence Based Complementary and Alternative Medicine, 2014: 432650. https://doi.org/10.1155/2014/432650
  • 43. Scholz, R., Sobotka, M., Caramoy, A., Stempfl, T., Moehle, C. & Langmann, T. 2015. Minocycline counter-regulates pro-inflammatory microglia responses in the retina and protects from degeneration. Journal of Neuroinflammation, 12: 209. https://doi.org/10.1186/s12974-015-0431-4
  • 44. Seve, P., Cacoub, P., Bodaghi, B., Trad, S., Sellam, J., Bellocq, D., Bielefeld, P., Sene, D., Kaplanski, G., Monnet, D., Brezin, A., Weber, M., Saadoun, D., Chiquet, C. & Kodjikian, L. 2017. Uveitis: Diagnostic work-up. A literature review and recommendations from an expert committee. Autoimmunity Reviews, 16(12): 1254-1264. https://doi.org/10.1016/j.autrev.2017.10.010
  • 45. Stoddard, A.R., Koetje, L.R., Mitchell, A.K., Schotanus, M.P. & Ubels, J.L. 2013. Bioavailability of antioxidants applied to stratified human corneal epithelial cells. Journal of Ocular Pharmacology and Therapeutics, 29(7): 681-687. https://doi.org/10.1089/jop.2013.0014
  • 46. Sugita, S., Takase, H., Taguchi, C. & Mochizuki, M. 2007. The role of soluble TNF receptors for TNF-alpha in uveitis. Investigative Ophthalmology & Visual Science, 48(7): 3246-3252. https://doi.org/10.1167/iovs.06-1444
  • 47. Suttorp-Schulten, M.S. & Rothova, A. 1996. The possible impact of uveitis in blindness: a literature survey. BMJ Open Ophthalmology, 80(9): 844-848. https://doi.org/10.1136/bjo.80.9.844
  • 48. Tagirasa, R., Parmar, S., Barik, M.R., Devadas, S. & Basu, S. 2017. Autoreactive T Cells in Immunopathogenesis of TB-Associated Uveitis. Investigative Ophthalmology & Visual Science, 58(13): 5682-5691. https://doi.org/10.1167/iovs.17-22462
  • 49. Ugan, R.A. & Un, H. 2020. The Protective Roles of Butein on Indomethacin Induced Gastric Ulcer in Mice. The Eurasian Journal of Medicine, 52(3): 265-270. https://doi.org/10.5152/eurasianjmed.2020.20022
  • 50. Un, H., Ugan, R.A., Kose, D., Yayla, M., Tastan, T.B., Bayir, Y. & Halici, Z. 2022. A new approach to sepsis treatment by rasagiline: a molecular, biochemical and histopathological study. Molecular Biology Reports, 49: 3875-3883. https://doi.org/10.1007/s11033-022-07235-1
  • 51. Wang, L. & Weller, C.L. 2006. Recent advances in extraction of nutraceuticals from plants. Trends in Food Science & Technology, 17(6): 300-312.
  • 52. Wang, T., Men, R., Hu, M., Fan, X., Yang, X., Huang, X., Ye, T. & Yang, L. 2018. Protective effects of Punica granatum (pomegranate) peel extract on concanavalin A-induced autoimmune hepatitis in mice. Biomedicine & Pharmacotherapy, 100: 213-220. https://doi.org/10.1016/j.biopha.2017.12.110
  • 53. Xu, J., Guo, C.J., Yang, J.J., Wei, J.Y., Li, Y.F., Pang, W., Jiang, Y.G. & Cheng, S. 2005. Intervention of antioxidant system function of aged rats by giving fruit juices with different antioxidant capacities. Zhonghua Yu Fang Yi Xue Za Zhi, 39(2): 80-83.
  • 54. Xu, X., Li, H., Hou, X., Li, D., He, S., Wan, C., Yin, P., Liu, M., Liu, F. & Xu, J. 2015. Punicalagin Induces Nrf2/HO-1 Expression via Upregulation of PI3K/AKT Pathway and Inhibits LPS-Induced Oxidative Stress in RAW264.7 Macrophages. Mediators of Inflammation, 2015: 380218. https://doi.org/10.1155/2015/380218
  • 55. Yadav, U.C., Kalariya, N.M. & Ramana, K.V. 2011. Emerging role of antioxidants in the protection of uveitis complications. Current Medicinal Chemistry, 18(6): 931-942. https://doi.org/10.2174/092986711794927694
  • 56. Yadav, U.C., Subramanyam, S. & Ramana, K.V. 2009. Prevention of endotoxin-induced uveitis in rats by benfotiamine, a lipophilic analogue of vitamin B1. Investigative Ophthalmology & Visual Science, 50(5): 2276-2282. https://doi.org/10.1167/iovs.08-2816
  • 57. Yaidikar, L., Byna, B. & Thakur, S.R. 2014. Neuroprotective effect of punicalagin against cerebral ischemia reperfusion-induced oxidative brain injury in rats. Journal of Stroke and Cerebrovascular Diseases, 23(10): 2869-2878. https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.07.020
  • 58. Yayla, M., Cadirci, E., Halici, Z., Bakan, F., Ay, N., Demirci, S., Karaman, A. & Sahin, F. 2020. Regenerative Effect of Resorbable Scaffold Embedded Boron-Nitride/Hydroxyapatite Nanoparticles in Rat Parietal Bone. Journal of Nanoscience and Nanotechnology, 20(2): 680-691. https://doi.org/10.1166/jnn.2020.17128
  • 59. Yoshida, Y., Yamagishi, S., Matsui, T., Jinnouchi, Y., Fukami, K., Imaizumi, T. & Yamakawa, R. 2009. Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathy. Diabetes/Metabolism Research and Reviews, 25(7): 678-686. https://doi.org/10.1002/dmrr.1007
  • 60. Zhang, N., Yu, S., Liu, X. & Lu, H. 2017. Low Dose of Lipopolysaccharide Pretreatment Preventing Subsequent Endotoxin-Induced Uveitis Is Associated with PI3K/AKT Pathway. Journal of Immunology Research, 2017: 1273940. https://doi.org/10.1155/2017/1273940
There are 60 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section Research Article/Araştırma Makalesi
Authors

Tuğba Nurcan Yüksel 0000-0001-5092-1674

Muhammed Yayla 0000-0002-0659-3084

Duygu Köse 0000-0002-3468-1567

Rüstem Anıl Uğan 0000-0002-4837-2343

Erdem Toktay 0000-0002-7447-6023

Pinar Aksu Kılıçle 0000-0002-3567-5775

Elif Çadırcı 0000-0003-0836-7205

Zekai Halıcı 0000-0001-6854-6059

Project Number NKUBAP.02.GA.20.240
Publication Date April 15, 2023
Submission Date July 19, 2022
Acceptance Date October 28, 2022
Published in Issue Year 2023 Volume: 24 Issue: 1

Cite

APA Yüksel, T. N., Yayla, M., Köse, D., Uğan, R. A., et al. (2023). INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS. Trakya University Journal of Natural Sciences, 24(1), 11-20. https://doi.org/10.23902/trkjnat.1145462
AMA Yüksel TN, Yayla M, Köse D, Uğan RA, Toktay E, Aksu Kılıçle P, Çadırcı E, Halıcı Z. INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS. Trakya Univ J Nat Sci. April 2023;24(1):11-20. doi:10.23902/trkjnat.1145462
Chicago Yüksel, Tuğba Nurcan, Muhammed Yayla, Duygu Köse, Rüstem Anıl Uğan, Erdem Toktay, Pinar Aksu Kılıçle, Elif Çadırcı, and Zekai Halıcı. “INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica Granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS”. Trakya University Journal of Natural Sciences 24, no. 1 (April 2023): 11-20. https://doi.org/10.23902/trkjnat.1145462.
EndNote Yüksel TN, Yayla M, Köse D, Uğan RA, Toktay E, Aksu Kılıçle P, Çadırcı E, Halıcı Z (April 1, 2023) INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS. Trakya University Journal of Natural Sciences 24 1 11–20.
IEEE T. N. Yüksel, M. Yayla, D. Köse, R. A. Uğan, E. Toktay, P. Aksu Kılıçle, E. Çadırcı, and Z. Halıcı, “INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS”, Trakya Univ J Nat Sci, vol. 24, no. 1, pp. 11–20, 2023, doi: 10.23902/trkjnat.1145462.
ISNAD Yüksel, Tuğba Nurcan et al. “INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica Granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS”. Trakya University Journal of Natural Sciences 24/1 (April 2023), 11-20. https://doi.org/10.23902/trkjnat.1145462.
JAMA Yüksel TN, Yayla M, Köse D, Uğan RA, Toktay E, Aksu Kılıçle P, Çadırcı E, Halıcı Z. INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS. Trakya Univ J Nat Sci. 2023;24:11–20.
MLA Yüksel, Tuğba Nurcan et al. “INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica Granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS”. Trakya University Journal of Natural Sciences, vol. 24, no. 1, 2023, pp. 11-20, doi:10.23902/trkjnat.1145462.
Vancouver Yüksel TN, Yayla M, Köse D, Uğan RA, Toktay E, Aksu Kılıçle P, Çadırcı E, Halıcı Z. INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS. Trakya Univ J Nat Sci. 2023;24(1):11-20.

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