Skip to main content

Advertisement

Log in

Oral administration of nano-tyrosol reversed the diabetes-induced liver damage in streptozotocin-induced diabetic rats

  • Research article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Objectives

The present study was designed to evaluate the effects of Tyrosol and Nano-tyrosol on the cellular arrangement, collagen disposition, protein level of insulin receptor (INSR), and superoxide dismutase (SOD) activity in both control and streptozotocin-induced diabetic rats.

Methods

Type 2 Diabetes (T2D) was induced in rats by a single intraperitoneal injection of streptozotocin (50 mg/kg). Experimental rats were administered Tyrosol and Nano-tyrosol 1 ml intra-gastrically at a dose of 20 mg/kg once a day for 30 days. Then, rats were sacrificed according to ethical principles. Livers were removed and processed for histological studies using the paraffin technique. Furthermore, non-paraffin sections were used for the INSR-1 western blot technique.

Results

At the end of the experiments, the rats in diabetic control and plain niosome groups exhibited a significant increase in collagen disposition (p < 0.001), and apoptotic cells (p < 0.001), as well as decreased total protein levels of INSR (p < 0.001), and SOD activity (p < 0.001) in the hepatic cells. Oral administration of Tyrosol and Nano-tyrosol to diabetic rats reversed all the above-mentioned parameters to near normal levels (p < 0.001). Nano-tyrosol showed the highest significant effect rather than Tyrosol.

Conclusion

The results of the present study suggested the beneficial effects of Tyrosol and especially Nano-tyrosol on decreasing the adverse effects of diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011;94(3):311–21.

    Article  PubMed  Google Scholar 

  2. Chandramohan R, Pari L, Rathinam A, Sheikh BA. Tyrosol, a phenolic compound, ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats. Chemico-Biol Interact. 2015;229:44–54.

    Article  CAS  Google Scholar 

  3. Dada AO, Ogundele SO, Amisu MA, Williams A. Prescription pattern and treatment target in patients with type 2 diabetes attending a tertiary health center in Lagos. J Diabetol. 2021;12(1):36.

    Article  Google Scholar 

  4. MO J. Diabetes Mellitus. In Cecil Text Book of Medicine; 2000.

  5. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263–73.

    Article  CAS  PubMed  Google Scholar 

  6. Targher G, Byrne CD. Nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications. J Clin Endocrinol Metabolism. 2013;98(2):483–95.

    Article  CAS  Google Scholar 

  7. Markova M, Pivovarova O, Hornemann S, Sucher S, Frahnow T, Wegner K, et al. Isocaloric diets high in animal or plant protein reduce liver fat and inflammation in individuals with type 2 diabetes. Gastroenterology. 2017;152(3):571–85. e8.

    Article  CAS  PubMed  Google Scholar 

  8. Tian W, Chen L, Zhang L, Wang B, Li X, Fan K, et al. Effects of ginsenoside Rg1 on glucose metabolism and liver injury in streptozotocin-induced type 2 diabetic rats. Genet Mol Res. 2017;16(1):gmr16019463.

    Article  Google Scholar 

  9. Newgard CB. Interplay between lipids and branched-chain amino acids in development of insulin resistance. Cell Metabol. 2012;15(5):606–14.

    Article  CAS  Google Scholar 

  10. Feldman MFL, Brandt LJ, editors. Non-alcoholic fatty liver disease. ELSEVIER; 2006.

  11. Lans CA. Ethnomedicines used in Trinidad and Tobago for urinary problems and diabetes mellitus. J Ethnobiol Ethnomed. 2006;2(1):1–11.

    Article  Google Scholar 

  12. Kono Y, Fridovich I. Superoxide radical inhibits catalase. J Biol Chem. 1982;257(10):5751–4.

    Article  CAS  PubMed  Google Scholar 

  13. Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007;87(1):315–424.

    Article  CAS  PubMed  Google Scholar 

  14. Bigagli E, Lodovici M. Circulating oxidative stress biomarkers in clinical studies on type 2 diabetes and its complications. Oxidative medicine and cellular longevity. 2019;2019.

  15. Zhu A, Yang X, Sun M, Zhang Z, Li M. Associations between INSR and MTOR polymorphisms in type 2 diabetes mellitus and diabetic nephropathy in a Northeast Chinese Han population. Genet Mol Res. 2015;14(1):1808–18.

    Article  CAS  PubMed  Google Scholar 

  16. Okamoto H, Obici S, Accili D, Rossetti L. Restoration of liver insulin signaling in Insr knockout mice fails to normalize hepatic insulin action. J Clin Investig. 2005;115(5):1314–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Santoleri D, Titchenell PM. Resolving the paradox of hepatic insulin resistance. Cell Mol Gastroenterol Hepatol. 2019;7(2):447–56.

    Article  PubMed  Google Scholar 

  18. Karković Marković A, Torić J, Barbarić M, Jakobušić Brala C. Hydroxytyrosol, tyrosol and derivatives and their potential effects on human health. Molecules. 2019;24(10):2001.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Chandramohan R, Pari L. Anti-inflammatory effects of tyrosol in streptozotocin-induced diabetic Wistar rats. J Funct Foods. 2016;27:17–28.

    Article  CAS  Google Scholar 

  20. Castro-Barquero S, Lamuela-Raventós RM, Doménech M, Estruch R. Relationship between Mediterranean dietary polyphenol intake and obesity. Nutrients. 2018;10(10):1523.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Cicerale S, Lucas L, Keast R. Biological activities of phenolic compounds present in virgin olive oil. Int J Mol Sci. 2010;11(2):458–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chandramohan R, Saravanan S, Pari L. Beneficial effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats. Pharm Biol. 2017;55(1):1631–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pacifici F, Farias CLA, Rea S, Capuani B, Feraco A, Coppola A, et al. Tyrosol May Prevent Obesity by Inhibiting Adipogenesis in 3T3-L1 Preadipocytes. Oxidative medicine and cellular longevity. 2020;2020.

  24. Neveu V, Perez-Jiménez J, Vos F, Crespy V, du Chaffaut L, Mennen L, et al. Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database. 2010;2010.

  25. Stiuso P, Bagarolo ML, Ilisso CP, Vanacore D, Martino E, Caraglia M, et al. Protective effect of tyrosol and S-adenosylmethionine against ethanol-induced oxidative stress of Hepg2 cells involves sirtuin 1, P53 and Erk1/2 signaling. Int J Mol Sci. 2016;17(5):622.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sun L, Fan H, Yang L, Shi L, Liu Y. Tyrosol prevents ischemia/reperfusion-induced cardiac injury in H9c2 cells: involvement of ROS, Hsp70, JNK and ERK, and apoptosis. Molecules. 2015;20(3):3758–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sun Y, Zhou D, Shahidi F. Antioxidant properties of tyrosol and hydroxytyrosol saturated fatty acid esters. Food Chem. 2018;245:1262–8.

    Article  CAS  PubMed  Google Scholar 

  28. H D. Microscopic Anatomy. Springer; 2010.

  29. Moghassemi S, Hadjizadeh A. Nano-niosomes as nanoscale drug delivery systems: an illustrated review. J Controlled Release. 2014;185:22–36.

    Article  CAS  Google Scholar 

  30. Kazi KM, Mandal AS, Biswas N, Guha A, Chatterjee S, Behera M, et al. Niosome: a future of targeted drug delivery systems. J Adv Pharm Tech Res. 2010;1(4):374.

    Article  Google Scholar 

  31. Nematollahi MH, Pardakhty A, Torkzadeh-Mahanai M, Mehrabani M, Asadikaram G. Changes in physical and chemical properties of niosome membrane induced by cholesterol: a promising approach for niosome bilayer intervention. RSC Adv. 2017;7(78):49463–72.

    Article  CAS  Google Scholar 

  32. Moghassemi S, Hadjizadeh A, Omidfar K. Formulation and characterization of bovine serum albumin-loaded niosome. AAPS PharmSciTech. 2017;18(1):27–33.

    Article  CAS  PubMed  Google Scholar 

  33. Arora R. Advances in niosome as a drug carrier: a review. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm. 2016;1(1).

  34. Punithavathi VR, Prince PSM, Kumar R, Selvakumari J. Antihyperglycaemic, antilipid peroxidative and antioxidant effects of gallic acid on streptozotocin induced diabetic Wistar rats. Eur J Pharmacol. 2011;650(1):465–71.

    Article  CAS  PubMed  Google Scholar 

  35. Sheikh BA, Pari L, Rathinam A, Chandramohan R. Trans-anethole, a terpenoid ameliorates hyperglycemia by regulating key enzymes of carbohydrate metabolism in streptozotocin induced diabetic rats. Biochimie. 2015;112:57–65.

    Article  CAS  PubMed  Google Scholar 

  36. Coskun O, Kanter M, Korkmaz A, Oter S. Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas. Pharmacol Res. 2005;51(2):117–23.

    Article  CAS  PubMed  Google Scholar 

  37. Jemai H, El Feki A, Sayadi S. Antidiabetic and antioxidant effects of hydroxytyrosol and oleuropein from olive leaves in alloxan-diabetic rats. J Agric Food Chem. 2009;57(19):8798–804.

    Article  CAS  PubMed  Google Scholar 

  38. Vlachogianni IC, Fragopoulou E, Kostakis IK, Antonopoulou S. In vitro assessment of antioxidant activity of tyrosol, resveratrol and their acetylated derivatives. Food Chem. 2015;177:165–73.

    Article  CAS  PubMed  Google Scholar 

  39. Lee D-H, Kim Y-J, Kim MJ, Ahn J, Ha T-Y, Lee SH, et al. Pharmacokinetics of tyrosol metabolites in rats. Molecules. 2016;21(1):128.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lee H, Im SW, Jung CH, Jang YJ, Ha TY, Ahn J. Tyrosol, an olive oil polyphenol, inhibits ER stress-induced apoptosis in pancreatic β-cell through JNK signaling. Biochem Biophys Res Commun. 2016;469(3):748–52.

    Article  CAS  PubMed  Google Scholar 

  41. Kang GG, Francis N, Hill R, Waters D, Blanchard C, Santhakumar AB. Dietary polyphenols and gene expression in molecular pathways associated with type 2 diabetes mellitus: A Review. Int J Mol Sci. 2020;21(1):140.

    Article  CAS  Google Scholar 

  42. Cañuelo A, Gilbert-López B, Pacheco-Liñán P, Martínez-Lara E, Siles E, Miranda-Vizuete A. Tyrosol, a main phenol present in extra virgin olive oil, increases lifespan and stress resistance in Caenorhabditis elegans. Mech Ageing Dev. 2012;133(8):563–74.

    Article  PubMed  Google Scholar 

  43. Tuck KL, Freeman MP, Hayball PJ, Stretch GL, Stupans I. The in vivo fate of hydroxytyrosol and tyrosol, antioxidant phenolic constituents of olive oil, after intravenous and oral dosing of labeled compounds to rats. J Nutr. 2001;131(7):1993–6.

    Article  CAS  PubMed  Google Scholar 

  44. de la P Ro, MEMn D, Ruíz-Gutíerrez V, Flavill JA, Hoult JRS. Effects of virgin olive oil phenolics on scavenging of reactive nitrogen species and upon nitrergic neurotransmission. Life Sci. 2001;69(10):1213–22.

    Article  Google Scholar 

  45. Bertelli AA, Migliori M, Panichi V, Longoni B, Origlia N, Ferretti A, et al. Oxidative stress and inflammatory reaction modulation by white wine. Ann N Y Acad Sci. 2002;957(1):295–301.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank the IAUTMU’s Herbal pharmacology research center and animal room for their support and equipment.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

Authors

Contributions

Jafari-Rastegar N., Hosseininia HS., and Jalilvand E. acquired the animal data. Khakpai F. and Naseroleslami N. wrote the manuscript and analyzed the data. Mousavi-Niri N. was responsible for the study design and interpretation of results.

Corresponding author

Correspondence to Neda Mousavi-Niri.

Ethics declarations

Author Declarations

The authors declared no potential conflicts of interest to the research, authorship, and/or publication of this article.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jafari-Rastegar, N., Hosseininia, HS., Jalilvand, E. et al. Oral administration of nano-tyrosol reversed the diabetes-induced liver damage in streptozotocin-induced diabetic rats. J Diabetes Metab Disord 22, 297–305 (2023). https://doi.org/10.1007/s40200-022-01133-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-022-01133-w

Keywords

Navigation