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Immunomodulatory and Anti- Inflammatory Effect of Thymoquinone on Rat Liver and Kidneys

Year 2023, Volume: 18 Issue: 3, 95 - 101, 20.12.2023

Abstract

The Nigella sativa plant has a very long medical history. It has been used by ancient Egyptians for many purposes. Studies have reported that the plant has antibacterial, antifungal, anticancer, antidiabetic, antioxidant, and immunomodulation effects. The main active ingredient of the plant is a substance called thymoquinone. The aim of the present study was to investigate the immunomodulatory and anti-inflammatory effects of thymoquinone on rat liver and kidneys. Rats were shared into 5 groups the first group (1 mg/kg thymoquinone, intraperitoneally), the second group (2 mg/kg thymoquinone, intraperitoneally), the third group (10 mg/kg thymoquinone, gavage), the fourth group (20 mg/kg thymoquinone, gavage), and control group. The groups contained 7 rats and the experiment continued for 42 days. The localization and expression of interleukin 2, interleukin 4, interferon gamma, and tumor necrosis factor alphain the liver and kidneys are shown in vivo, and the immunomodulation effects of thymoquinone in the system have been shown. The effects of thymoquinone differ according to the cytokine type, administration methods, and dose. As a result, the present findings demonstrated that the immunomodulatory effect of thymoquinone on the liver and kidneys varies according to the organ, application method, and application dose. For interleukin 2, the most effective form of administration in the liver is intraperitoneal and low dose; for kidneys, it is a low-dose gavage administration. For interleukin 4, low-dose gavage administration has been observed to be more effective in the liver and kidneys. Similarly, it is concluded that especially 10 mg/kg gavage applications are more effective for liver and kidneys in interferon gamma and tumor necrosis factor alpha expressions.

References

  • 1. D’Amelia V, Docimo T, Crocoll C, Rigano MM. Specialized metabolites and valuable molecules in crop and medicinal plants: the evolution of their use and strategies for their production. Genes. 2021;12(6):936. [CrossRef]
  • 2. Dehelean CA, Marcovici I, Soica C, et al. Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Molecules. 2021;26(4):1109. [CrossRef]
  • 3. Rauf A, Akram M, Anwar H, et al. Therapeutic potential of herbal medicine for the management of hyperlipidemia: latest updates. Environ Sci Pollut Res Int. 2022;29(27):40281-40301. [CrossRef]
  • 4. Kerry B, Simon M. Principles and Practice of Phytotherapy: Modern Herbal Medicine. 2nd ed. New York: Churchill Livingstone/Elsevier; 2013.
  • 5. Zohary D, Hopf M, Weiss E. Domestication of Plants in the Old World: The Origin and Spread of Domesticated Plants in Southwest Asia, Europe, and the Mediterranean Basin. Oxford: Oxford University Press; 2012.
  • 6. Woo CC, Kumar AP, Sethi G, Tan KHB. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol. 2012;83(4):443-451. [CrossRef]
  • 7. Çelik F, Göçmez C, Karaman H, et al. Therapeutic effects of thymoquinone in a model of neuropathic pain. Curr Ther Res Clin Exp. 2014;76:11-16. [CrossRef]
  • 8. Ojha S, Azimullah S, Mohanraj R, et al. Thymoquinone protects against myocardial ischemic injury by mitigating oxidative stress and inflammation. Evid Based Complement Alternat Med. 2015;4:1-12. [CrossRef]
  • 9. Güzelsoy P, Aydin S, Başaran N. Çörek otunun (Nigella sativa L.) aktif bileşeni timokinonun insan sağlığı üzerine olası etkileri. J Lit Pharm Sci. 2018;7(2):118-135. [CrossRef]
  • 10. Mahomoodally MF, Aumeeruddy MZ, Legoabe LJ, Montesano D, Zengin G. Nigella sativa L. and Its Active Compound thymoquinone in the Clinical Management of Diabetes: A Systematic Review. Int J Mol Sci. 2022;23(20):12111. [CrossRef]
  • 11. Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol. 2005;5(13-14):1749- 1770. [CrossRef]
  • 12. Kenawy SA, El-Sayed ME, Awad AS, Fayez AM, El-Naa MM. Effect of thymoquinone and omega-3 on intestinal ischemia/reperfusion induced hepatic dysfunction in rats. Br J Pharmacol. 2014;5(5):169-176. [CrossRef]
  • 13. Al-Ali A, Alkhawajah AA, Randhawa MA, Shaikh NA. Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J Ayub Med Coll Abbottabad. 2008;20(2):25-27.
  • 14. Boskabady MH, Keyhanmanesh R, Khameneh S, Doostdar Y, Khakzad MR. Potential immunomodulation effect of the extract of Nigella sativa on ovalbumin sensitized guinea pigs. J Zhejiang Univ Sci B. 2011;12(3):201-209. [CrossRef]
  • 15. Ertuğrul T, Tutuncu Ş, Ozdemır B, Delıce N. Possible effect of thymoquinone on mast cell number and chymase, IL-4 and IFN-γ expression in rat spleen. Med Weter. 2021;77(10):6580-2021. [CrossRef]
  • 16. Gholamnezhad Z, Boskabady MH, Hosseini M. Effect of Nigella sativa on immune response in treadmill exercised rat. BMC Complement Altern Med. 2014;14:437. [CrossRef]
  • 17. Alshatwi AA. Bioactivity-guided identification to delineate the immunomodulatory effects of methanolic extract of Nigella sativa seed on human peripheral blood mononuclear cells. Chin J Integr Med. 2014:1-6. [CrossRef]
  • 18. Abuharfeil NM, Salim M, Von Kleist S. Augmentation of natural killer cell activity in vivo against tumour cells by some wild plants from Jordan. Phytother Res. 2001;15(2):109-113. [CrossRef]
  • 19. Robinson MW, Harmon C, O’Farrelly C. Liver immunology and its role in inflammation and homeostasis. Cell Mol Immunol. 2016;13(3):267-276. [CrossRef]
  • 20. Parajuli S, Hidalgo LG, Foley D. Immunology of simultaneous liver and kidney transplants with identification and prevention of rejection. Front Transplant. 2022;1:991546. [CrossRef]
  • 21. Salem ML, Alenzi FQ, Attia WY. Thymoquinone, the active ingredient of Nigella sativa seeds, enhances survival and activity of antigenspecific CD8-positive T cells in vitro. Br J Biomed Sci. 2011;68(3):131-137. [CrossRef]
  • 22. Kaya M, Kara M, Ozbek H. Seed of corek otu (Nigella sativa) effect human cell and immunity system CD3+, CD4+, CD8+ Cells and effect a number of total leucocytes. J Gen Med. 2003;13(3):109-112.
  • 23. Al-Ghamdi MS. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol. 2001;76(1):45-48. [CrossRef]
  • 24. Haq A, Lobo PI, Al-Tufail M, Rama NR, Al-Sedairy ST. Immunomodulatory effect of Nigella sativa proteins fractionated by ion exchange chromatography. Int J Immunopharmacol. 1999;21(4):283-295. [CrossRef]
  • 25. Khazdair MR, Ghafari S, Sadeghi M. Possible therapeutic effects of Nigella sativa and its thymoquinone on COVID-19. Pharm Biol. 2021;59(1):696-703. [CrossRef]
  • 26. Crossmon G. A modification of Mallory’s connective tissue stain with a discussion of the principles involved. Anat Rec. 1937;69(1):33-38. [CrossRef]
  • 27. True L. Principles of immunohistochemistry. In: True L, ed. Atlas of Diagnostic Immunohistopathology. London: Gower Medical Publishing; 1990:16-22.
  • 28. Ertuğrul T, Tütüncü Ş, Çİftcİ G. Effect of probiotic on mast cell density and expression of tryptase, chymase, and TNF-α in the urinary bladder of rats with high cholesterol. Ank Univ Vet Fak Derg. 2022;69(3):273-280. [CrossRef]
  • 29. Caglar TA, Tutuncu S, Ustun B, Akdemir HU. A study of the therapeutic effects of resveratrol on blunt chest trauma-induced acute lung injury in rats and the potential role of endocan as a biomarker of inflammation inflammation. 2017;40(5):1803-1810.
  • 30. Randhawa MA, Alghamdi MS. Anticancer activity of Nigella sativa (black seed)—a review. Am J Chin Med. 2011;39(6):1075-1091. [CrossRef]
  • 31. Yuncu M, Sahin M, Bayat N, Sari I. Effects of Nigella sativa oil on rat liver development. Gaziantep Med J. 2013;19(3):180-184. [CrossRef]
  • 32. Cobourne-Duval MK, Taka E, Mendonca P, Soliman KFA. Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ-activated BV-2 microglia cells. J Neuroimmunol. 2018;320:87-97. [CrossRef]
  • 33. Günel C, Demirci B, Meteoğlu İ, Yilmaz M, Ömürlü İK, Kocatürk T. The anti-inflammatory effects of thymoquinone in a rat model of allergic rhinitis. TR-ENT. 2017;27(5):226-232. [CrossRef]
  • 34. Gholamnezhad Z, Rafatpanah H, Sadeghnia HR, Boskabady MH. Immunomodulatory and cytotoxic effects of Nigella sativa and thymoquinone n rat splenocytes. Food Chem Toxicol. 2015;86:72-80. [CrossRef]
  • 35. Osman MT, Al-Duboni G, Taha BI, Muhamed LA. Refractory coeliac disease; role of Nigella sativa as immunomodulator. BJMMR. 2012;2(4):527-535. [CrossRef]

Timokinonun Rat Karaciğer ve Böbrekleri Üzerindeki İmmunmodülatör ve Antiinflamatuvar Etkisi

Year 2023, Volume: 18 Issue: 3, 95 - 101, 20.12.2023

Abstract

Nigella sativa bitkisinin çok uzun bir tıbbi geçmişi vardır. Antik Mısırlılar tarafından birçok amaç için kullanılmıştır. Çalışmalar bitkinin antibakteriyel, antifungal, antikanser, antidiyabetik, antioksidan ve immünomodülasyon etkilerine sahip olduğunu rapor etmiştir. Bitkinin ana etken maddesi timokinon adlı bir madde içerir. Bu çalışmanın amacı, timokinonun sıçan karaciğer ve böbreklerindeki immünomodülatör ve anti-inflamatuar etkilerini incelemekti. Sıçanlar, birinci grup (1 mg/ kg timokinon, intraperitoneal), ikinci grup (2 mg/kg timokinon, intraperitoneal), üçüncü grup (10 mg/kg timokinon, gastrik gavaj), dördüncü grup (20 mg/kg timokinon, gastrik gavaj) ve kontrol grubuna ayrıldı. Gruplar yedi sıçandan oluşturuldu ve deney 42 gün boyunca devam etti. Karaciğer ve böbreklerdeki interlökin-2, interlökin-4, interferon gama ve tümör nekroz faktörü alfanın lokalizasyonu ve ekspresyonu in vivo olarak gösterildi ve sistemde timokinonun immünomodülasyon etkileri gösterildi. Sonuç olarak, mevcut bulgular, timokinonun karaciğer ve böbrekler üzerindeki immünomodülatör etkisinin organa, uygulama yöntemine ve uygulama dozuna bağlı olarak değiştiğini göstermektedir. Interlökin-2 için karaciğerde intraperitoneal ve düşük dozun en etkili uygulama şekli olduğu; böbrekler için ise düşük doz gastrik gavaj uygulamasının daha etkili olduğu görülmüştür. İnterlökin-4 için ise karaciğer ve böbreklerde düşük doz gastrik gavaj uygulamasının
daha etkili olduğu gözlemlenmiştir. Benzer şekilde, özellikle 10 mg/kg gastrik gavaj uygulamalarının interferon gama ve tümör nekroz faktörü alfa ekspresyonu için karaciğer ve böbreklerde daha etkili olduğu sonucuna varılmıştır.

References

  • 1. D’Amelia V, Docimo T, Crocoll C, Rigano MM. Specialized metabolites and valuable molecules in crop and medicinal plants: the evolution of their use and strategies for their production. Genes. 2021;12(6):936. [CrossRef]
  • 2. Dehelean CA, Marcovici I, Soica C, et al. Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Molecules. 2021;26(4):1109. [CrossRef]
  • 3. Rauf A, Akram M, Anwar H, et al. Therapeutic potential of herbal medicine for the management of hyperlipidemia: latest updates. Environ Sci Pollut Res Int. 2022;29(27):40281-40301. [CrossRef]
  • 4. Kerry B, Simon M. Principles and Practice of Phytotherapy: Modern Herbal Medicine. 2nd ed. New York: Churchill Livingstone/Elsevier; 2013.
  • 5. Zohary D, Hopf M, Weiss E. Domestication of Plants in the Old World: The Origin and Spread of Domesticated Plants in Southwest Asia, Europe, and the Mediterranean Basin. Oxford: Oxford University Press; 2012.
  • 6. Woo CC, Kumar AP, Sethi G, Tan KHB. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol. 2012;83(4):443-451. [CrossRef]
  • 7. Çelik F, Göçmez C, Karaman H, et al. Therapeutic effects of thymoquinone in a model of neuropathic pain. Curr Ther Res Clin Exp. 2014;76:11-16. [CrossRef]
  • 8. Ojha S, Azimullah S, Mohanraj R, et al. Thymoquinone protects against myocardial ischemic injury by mitigating oxidative stress and inflammation. Evid Based Complement Alternat Med. 2015;4:1-12. [CrossRef]
  • 9. Güzelsoy P, Aydin S, Başaran N. Çörek otunun (Nigella sativa L.) aktif bileşeni timokinonun insan sağlığı üzerine olası etkileri. J Lit Pharm Sci. 2018;7(2):118-135. [CrossRef]
  • 10. Mahomoodally MF, Aumeeruddy MZ, Legoabe LJ, Montesano D, Zengin G. Nigella sativa L. and Its Active Compound thymoquinone in the Clinical Management of Diabetes: A Systematic Review. Int J Mol Sci. 2022;23(20):12111. [CrossRef]
  • 11. Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol. 2005;5(13-14):1749- 1770. [CrossRef]
  • 12. Kenawy SA, El-Sayed ME, Awad AS, Fayez AM, El-Naa MM. Effect of thymoquinone and omega-3 on intestinal ischemia/reperfusion induced hepatic dysfunction in rats. Br J Pharmacol. 2014;5(5):169-176. [CrossRef]
  • 13. Al-Ali A, Alkhawajah AA, Randhawa MA, Shaikh NA. Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J Ayub Med Coll Abbottabad. 2008;20(2):25-27.
  • 14. Boskabady MH, Keyhanmanesh R, Khameneh S, Doostdar Y, Khakzad MR. Potential immunomodulation effect of the extract of Nigella sativa on ovalbumin sensitized guinea pigs. J Zhejiang Univ Sci B. 2011;12(3):201-209. [CrossRef]
  • 15. Ertuğrul T, Tutuncu Ş, Ozdemır B, Delıce N. Possible effect of thymoquinone on mast cell number and chymase, IL-4 and IFN-γ expression in rat spleen. Med Weter. 2021;77(10):6580-2021. [CrossRef]
  • 16. Gholamnezhad Z, Boskabady MH, Hosseini M. Effect of Nigella sativa on immune response in treadmill exercised rat. BMC Complement Altern Med. 2014;14:437. [CrossRef]
  • 17. Alshatwi AA. Bioactivity-guided identification to delineate the immunomodulatory effects of methanolic extract of Nigella sativa seed on human peripheral blood mononuclear cells. Chin J Integr Med. 2014:1-6. [CrossRef]
  • 18. Abuharfeil NM, Salim M, Von Kleist S. Augmentation of natural killer cell activity in vivo against tumour cells by some wild plants from Jordan. Phytother Res. 2001;15(2):109-113. [CrossRef]
  • 19. Robinson MW, Harmon C, O’Farrelly C. Liver immunology and its role in inflammation and homeostasis. Cell Mol Immunol. 2016;13(3):267-276. [CrossRef]
  • 20. Parajuli S, Hidalgo LG, Foley D. Immunology of simultaneous liver and kidney transplants with identification and prevention of rejection. Front Transplant. 2022;1:991546. [CrossRef]
  • 21. Salem ML, Alenzi FQ, Attia WY. Thymoquinone, the active ingredient of Nigella sativa seeds, enhances survival and activity of antigenspecific CD8-positive T cells in vitro. Br J Biomed Sci. 2011;68(3):131-137. [CrossRef]
  • 22. Kaya M, Kara M, Ozbek H. Seed of corek otu (Nigella sativa) effect human cell and immunity system CD3+, CD4+, CD8+ Cells and effect a number of total leucocytes. J Gen Med. 2003;13(3):109-112.
  • 23. Al-Ghamdi MS. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol. 2001;76(1):45-48. [CrossRef]
  • 24. Haq A, Lobo PI, Al-Tufail M, Rama NR, Al-Sedairy ST. Immunomodulatory effect of Nigella sativa proteins fractionated by ion exchange chromatography. Int J Immunopharmacol. 1999;21(4):283-295. [CrossRef]
  • 25. Khazdair MR, Ghafari S, Sadeghi M. Possible therapeutic effects of Nigella sativa and its thymoquinone on COVID-19. Pharm Biol. 2021;59(1):696-703. [CrossRef]
  • 26. Crossmon G. A modification of Mallory’s connective tissue stain with a discussion of the principles involved. Anat Rec. 1937;69(1):33-38. [CrossRef]
  • 27. True L. Principles of immunohistochemistry. In: True L, ed. Atlas of Diagnostic Immunohistopathology. London: Gower Medical Publishing; 1990:16-22.
  • 28. Ertuğrul T, Tütüncü Ş, Çİftcİ G. Effect of probiotic on mast cell density and expression of tryptase, chymase, and TNF-α in the urinary bladder of rats with high cholesterol. Ank Univ Vet Fak Derg. 2022;69(3):273-280. [CrossRef]
  • 29. Caglar TA, Tutuncu S, Ustun B, Akdemir HU. A study of the therapeutic effects of resveratrol on blunt chest trauma-induced acute lung injury in rats and the potential role of endocan as a biomarker of inflammation inflammation. 2017;40(5):1803-1810.
  • 30. Randhawa MA, Alghamdi MS. Anticancer activity of Nigella sativa (black seed)—a review. Am J Chin Med. 2011;39(6):1075-1091. [CrossRef]
  • 31. Yuncu M, Sahin M, Bayat N, Sari I. Effects of Nigella sativa oil on rat liver development. Gaziantep Med J. 2013;19(3):180-184. [CrossRef]
  • 32. Cobourne-Duval MK, Taka E, Mendonca P, Soliman KFA. Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ-activated BV-2 microglia cells. J Neuroimmunol. 2018;320:87-97. [CrossRef]
  • 33. Günel C, Demirci B, Meteoğlu İ, Yilmaz M, Ömürlü İK, Kocatürk T. The anti-inflammatory effects of thymoquinone in a rat model of allergic rhinitis. TR-ENT. 2017;27(5):226-232. [CrossRef]
  • 34. Gholamnezhad Z, Rafatpanah H, Sadeghnia HR, Boskabady MH. Immunomodulatory and cytotoxic effects of Nigella sativa and thymoquinone n rat splenocytes. Food Chem Toxicol. 2015;86:72-80. [CrossRef]
  • 35. Osman MT, Al-Duboni G, Taha BI, Muhamed LA. Refractory coeliac disease; role of Nigella sativa as immunomodulator. BJMMR. 2012;2(4):527-535. [CrossRef]

Details

Primary Language English
Subjects Veterinary Histology and Embryology
Journal Section Research Articles
Authors

Tuğrul ERTUĞRUL

Publication Date December 20, 2023
Published in Issue Year 2023 Volume: 18 Issue: 3

Cite

APA ERTUĞRUL, T. (2023). Immunomodulatory and Anti- Inflammatory Effect of Thymoquinone on Rat Liver and Kidneys. Veterinary Sciences and Practices, 18(3), 95-101.
AMA ERTUĞRUL T. Immunomodulatory and Anti- Inflammatory Effect of Thymoquinone on Rat Liver and Kidneys. Veterinary Sciences and Practices. December 2023;18(3):95-101.
Chicago ERTUĞRUL, Tuğrul. “Immunomodulatory and Anti- Inflammatory Effect of Thymoquinone on Rat Liver and Kidneys”. Veterinary Sciences and Practices 18, no. 3 (December 2023): 95-101.
EndNote ERTUĞRUL T (December 1, 2023) Immunomodulatory and Anti- Inflammatory Effect of Thymoquinone on Rat Liver and Kidneys. Veterinary Sciences and Practices 18 3 95–101.
IEEE T. ERTUĞRUL, “Immunomodulatory and Anti- Inflammatory Effect of Thymoquinone on Rat Liver and Kidneys”, Veterinary Sciences and Practices, vol. 18, no. 3, pp. 95–101, 2023.
ISNAD ERTUĞRUL, Tuğrul. “Immunomodulatory and Anti- Inflammatory Effect of Thymoquinone on Rat Liver and Kidneys”. Veterinary Sciences and Practices 18/3 (December 2023), 95-101.
JAMA ERTUĞRUL T. Immunomodulatory and Anti- Inflammatory Effect of Thymoquinone on Rat Liver and Kidneys. Veterinary Sciences and Practices. 2023;18:95–101.
MLA ERTUĞRUL, Tuğrul. “Immunomodulatory and Anti- Inflammatory Effect of Thymoquinone on Rat Liver and Kidneys”. Veterinary Sciences and Practices, vol. 18, no. 3, 2023, pp. 95-101.
Vancouver ERTUĞRUL T. Immunomodulatory and Anti- Inflammatory Effect of Thymoquinone on Rat Liver and Kidneys. Veterinary Sciences and Practices. 2023;18(3):95-101.

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