Skip to main navigation menu Skip to main content Skip to site footer

Research Articles

Vol. 12 No. 2 (2025)

Comparative therapeutic efficacy of Olea europaea L. leaf extract and bone marrow-derived mesenchymal stem cells in ameliorating streptozotocin-induced hepatic and splenic damage in pregnant Rats: Mechanisms of antioxidant and anti-apoptotic protection

DOI
https://doi.org/10.14719/pst.6955
Submitted
28 December 2024
Published
10-03-2025 — Updated on 01-04-2025
Versions

Abstract

Mesenchymal stem cells (MSCs) are multipotent stromal cells with remarkable plasticity, enabling them to differentiate into various tissue-specific cell types. MSCs play a pivotal role in tissue repair, hematopoiesis and immunomodulation. This study aimed to evaluate and compare the protective effects of olive leaf extract (OLE), bone marrow-derived mesenchymal stem cells (BM-MSCs) and their combination against hepatic and splenic toxicity in a rat model of gestational diabetes induced by streptozotocin (STZ). Histopathological and immunohistochemical analyses of liver and spleen tissues were conducted to assess these effects. Methods: Pregnant female rats were divided into five groups (n = 10 per group): Control group: Rats received STZ at a dose of 35 mg/kg body weight. OLE group: Rats were administered olive leaf extract (OLE) at 200 mg/kg body weight. GD + OLE group: Rats with STZ-induced gestational diabetes (GD) were treated with OLE (200 mg/kg body weight). GD + MSCs group: Rats with STZ-induced GD were treated with BM-MSCs. GD + OLE + MSCs group: Rats with STZ-induced GD were treated with both OLE and BM-MSCs. Results: STZ administration induced significant histopathological and immunohistochemical alterations in the liver and spleen tissues of pregnant femal rats. Treatment with OLE, BM-MSCs, or their combination markedly ameliorated these STZ-induced deteriorations, with the combined treatment showing the most pronounced protective effects. Conclusion: The findings demonstrate that both BM-MSCs and OLE exert protective effects against hepatotoxicity and splenic toxicity in a rat model of gestational diabetes. The combination of OLE and BM-MSCs exhibited synergistic benefits, highlighting their potential as therapeutic agents for mitigating organ damage in gestational diabetes.

References

  1. Jiang S, Liu A, Ma W, Liu X, Luo P, Zhan M, et al. Lactobacillus gasseri CKCC1913 medi-ated modulation of the gut–liver axis alleviated insulin resistance and liver damage induced by type 2 diabetes. Food Function. 2023;14:8504-20. https://doi.org/10.1039/D3FO01701J
  2. Karigidi KO, Akintimehin ES, Omoboyowa DA, Adetuyi FO, Olaiya CO. Effect of Curcu-ligo pilosa-supplemented diet on blood sugar, lipid metabolism, hepatic oxidative stress, and carbohydrate metabolism enzymes in streptozotocin-induced diabetic rats. Journal of Dia-betes & Metabolic Disorders 2020;19:1173-84. https://doi.org/10.1007/s40200-020-00618-w
  3. Bolajoko EB, Akinosun OM, Khine AA. Hyperglycemia-induced oxidative stress in the development of diabetic foot ulcers. In: Preedy VR, editor. Diabetes. 2nd ed. Academic Press; 2020. p. 35-48.
  4. Ott KC, Bi M, Scorletti F, Ranginwala SA, Marriott WS, Peiro JL, et al. The interplay be-tween prenatal liver growth and lung development in congenital diaphragmatic hernia. Frontiers in Pediatrics 2022;10:213. https://doi.org/10.3389/fped.2022.983492
  5. Owrangi S, Paik JM, Golabi P, de Avila L, Hashida R, Nader A, et al. Meta-Analysis: Global Prevalence and Mortality of Cirrhosis in Metabolic Dysfunction-Associated Steatotic Liver Disease. Alimentary Pharmacology & Therapeutics. 2025;61:433-43. https://doi.org/10.1111/apt.18451
  6. Fromenty B, Roden M. Mitochondrial alterations in fatty liver diseases Journal of Hepa-tology. 2023;78:415-29. https://doi.org/10.1016/j.jhep.2022.09.020
  7. ?ahin S, Bilgin M. Olive tree (Olea europaea L.) leaf as a waste by-product of table olive and olive oil industry: a review. Journal of the Science of Food and Agriculture. 2018;98:1271-79. https://doi.org/10.1002/jsfa.8619
  8. Castro AJ, Lima-Cabello E, Alché JD. Identification of seed storage proteins as the major constituents of the extra virgin olive oil proteome. Food Chemistry X. 2020;7:100099. https://doi.org/10.1016/j.fochx.2020.100099
  9. Susalit E, Agus N, Effendi I, Tjandrawinata RR, Nofiarny D, Perrinjaquet-Moccetti T, et al. Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: Com-parison with Captopril. Phytomedicine. 2011;18:251-58. https://doi.org/10.1016/j.phymed.2010.08.016
  10. Acar-Tek N, A?agündüz D. Olive leaf (Olea europaea L. folium): Potential effects on gly-cemia and lipidemia. Annals of Nutrition and Metabolism. 2020;76:10-15. https://doi.org/10.1159/000505508
  11. Stevens Y, Winkens B, Jonkers D, Masclee A. The effect of olive leaf extract on cardio-vascular health markers: a randomized placebo-controlled clinical trial. European Journal of Nutrition. 2021;60:2111-20. https://doi.org/10.1007/s00394-020-02397-9
  12. Huang S, Leung V, Peng S, Li L, Lu FJ, Wang T, et al. Developmental definition of MSCs: new insights into pending questions. Cell Reprogram. 2011;13:465-72. https://doi.org/10.1089/cell.2011.0045
  13. El-Sayed ME, Atwa A, Sofy AR, Helmy YA, Amer K, Seadawy MG, et al. Mesenchymal stem cell transplantation in burn wound healing: uncovering the mechanisms of local re-generation and tissue repair. Histochemistry and Cell Biology. 2023. https://doi.org/10.1007/s00418-023-02244-y
  14. Bahsoun S, Coopman K, Akam EC. The impact of cryopreservation on bone marrow-derived mesenchymal stem cells: a systematic review. Journal of Translational Medicine. 2019;17:397. https://doi.org/10.1186/s12967-019-02136-7
  15. Li XW, Feng LX, Zhu X, Liu Q, Wang HS, Wu X, et al. Human umbilical cord blood mon-onuclear cells protect against renal tubulointerstitial fibrosis in cisplatin-treated rats. Bio-medicine & Pharmacotherapy. 2020;121:109310. https://doi.org/10.1016/j.biopha.2019.109310
  16. Luo J, Zhao X, Tan Z, Su Z, Meng F, Zhang M. Mesenchymal-like progenitors derived from human embryonic stem cells promote recovery from acute kidney injury via paracrine ac-tions. Cytotherapy. 2013;15:649-62. https://doi.org/10.1016/j.jcyt.2013.01.009
  17. Gunawardena TNA, Rahman MT, Abdullah BJJ, Abu Kasim NH. Conditioned media de-rived from mesenchymal stem cell cultures: the next generation for regenerative medicine. Journal of Tissue Engineering and Regenerative Medicine. 2019;13:569-86. https://doi.org/10.1002/term.2806
  18. Semedo P, Palasio CG, Oliveira CD, Feitoza CQ, Gonçalves GM, Cenedeze MA, et al. Early modulation of inflammation by mesenchymal stem cell after acute kidney injury. Interna-tional Immunopharmacology. 2009;9:677-82. https://doi.org/10.1016/j.intimp.2008.12.008
  19. Zhang Y, Ye C, Wang G, Gao Y, Tan K, Zhuo Z, et al. Kidney-targeted transplantation of mesenchymal stem cells by ultrasound-targeted microbubble destruction promotes kidney repair in diabetic nephropathy rats. BioMed Research International. 2013;2013:526367. https://doi.org/10.1155/2013/526367
  20. Alkhathami AG, El-Fakharany EM, El-Sayed MH, Atwa A, Ali FK, Hamad N, et al. Chemopreventive effect of Pistacia vera leaf extract against mammary carcinoma induced by dimethyl-benz(a)anthracene in vivo and in vitro: potential role of antioxidant, an-ti-inflammatory, and immune mechanisms. Food and Chemical Toxicology. 2025;196. https://doi.org/10.1016/j.fct.2024.115229
  21. Abdel-Reheim ES, Abd-Elmoneim AA, Hosni AA. Fatty-sucrosed diet/minimal dose of streptozotocin-treated rat: a novel model of gestational diabetes mellitus, metabolic and in-flammatory insight. Diabetes & Metabolism Journal. 2014;5(9).
  22. Suzuki YJ, Jain V, Park AM, Day RM. Oxidative stress and oxidant signaling in obstructive sleep apnea and associated cardiovascular diseases. Free Radical Biology and Medicine. 2006;40:1683-92. https://doi.org/10.1016/j.freeradbiomed.2006.01.008
  23. Giacometti J, Žauhar G, Žuvi? M. Optimization of ultrasonic-assisted extraction of major phenolic compounds from olive leaves (Olea europaea L.) using response surface method-ology. Foods. 2018.
  24. Abd Rabou MA, Atwa A, Massoud D, Asran AM, Alrayes ZR, Al-Otaibi AM, et al. Thera-peutic effect of mesenchymal stem cells and olive leaf extract against cytotoxicity induced by streptozotocin in gestational diabetes rats. Cellular Physiology and Biochemistry. 2024;58:702-21. https://doi.org/10.33594/000000744
  25. Abd Rabou MA, Alhumaidi Alotaibi M. Toxicity of Somadril compound on fetal ileum tissues of albino rats. Pakistan Journal of Biological Sciences. 2021;24:72-79. https://doi.org/10.3923/pjbs.2021.72.79
  26. Furman BL. Streptozotocin?induced diabetic models in mice and rats. Current protocols in pharmacology. 2015;70(1):5-47. https://doi.org/10.1002/0471141755.ph0547s70
  27. Suvarna KS, Layton C, Bancroft JD. Bancroft's Theory and Practice of Histological Tech-niques. 8th ed. Elsevier Health Sciences; 2018.
  28. Basha M. Immuno-techniques. In: Basha M, editor. Analytical Techniques in Biochemistry. New York, NY: Springer US; 2020. p. 77-102. https://doi.org/10.1007/978-1-0716-0134-1_7
  29. Queiroz LAD, Assis JB, Guimarães JPT, Sousa ESA, Milhomem AC, Sunahara KKS, et al. Endangered lymphocytes: the effects of alloxan and streptozotocin on immune cells in Type 1 induced diabetes. Mediators of Inflammation. 2021;2021:9940009. https://doi.org/10.1155/2021/9940009
  30. Nandini HS, Naik PR. Action of corilagin on hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats. Chemico-Biological Interactions. 2019;299:186-93. https://doi.org/10.1016/j.cbi.2018.12.012
  31. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Asso-ciation for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005-23. https://doi.org/10.1002/hep.25762
  32. Badr AB, Fouad DF. Anti-apoptotic and anti-inflammatory effects of olive leaf extract against cisplatin-induced nephrotoxicity in male rats. International Journal of Pharmacolo-gy. 2016;11:468-76.
  33. Elgebaly HA, Mosa NM, Allach M, El-Massry KF, El-Ghorab AH, Al Hroob AM, et al. Olive oil and leaf extract prevent fluoxetine-induced hepatotoxicity by attenuating oxidative stress, inflammation and apoptosis. Biomedicine & Pharmacotherapy. 2018;98:446-53. https://doi.org/10.1016/j.biopha.2017.12.101
  34. Vezza T, Rodríguez-Nogales A, Algieri F, Garrido-Mesa J, Romero M, Sánchez M, et al. The metabolic and vascular protective effects of olive (Olea europaea L.) leaf extract in di-et-induced obesity in mice are related to the amelioration of gut microbiota dysbiosis and to its immunomodulatory properties. Pharmacological Research. 2019;150:104487. https://doi.org/10.1016/j.phrs.2019.104487
  35. Franco MN, Galeano-Díaz T, López Ó, Fernández-Bolaños JG, Sánchez J, De Miguel C, et al. Phenolic compounds and antioxidant capacity of virgin olive oil. Food Chemistry. 2014;163:289-98. https://doi.org/10.1016/j.foodchem.2014.04.091
  36. Lapornik B, Prošek M, Golc Wondra A. Comparison of extracts prepared from plant by-products using different solvents and extraction time. Journal of Food Engineering. 2005;71:214-22. https://doi.org/10.1016/j.jfoodeng.2004.10.036
  37. Song L, Qu D, Zhang Q, Jiang J, Zhou H, Jiang R, et al. Phytosterol esters attenuate hepatic steatosis in rats with non-alcoholic fatty liver disease rats fed a high-fat diet. Scientific Re-ports. 2017;7:41604. https://doi.org/10.1038/srep41604
  38. Choi HS, Lee MJ, Na MS, Lee MY, Choi D. Antioxidant properties of Achyranthis radix extract in rats. Journal of Industrial and Engineering Chemistry. 2009;15:275-80. https://doi.org/10.1016/j.jiec.2008.12.001
  39. Petridis A, Therios I, Samouris G, Koundouras S, Giannakoula A. Effect of water deficit on leaf phenolic composition, gas exchange, oxidative damage and antioxidant activity of four Greek olive (Olea europaea L.) cultivars. Plant Physiology and Biochemistry. 2012;60:1-11. https://doi.org/10.1016/j.plaphy.2012.07.014
  40. Lambert de Malezieu M, Courtel P, Sleno L, Abasq M-L, Ramassamy C. Synergistic properties of bioavailable phenolic compounds from olive oil: electron transfer and neuroprotective properties. Nutritional Neuroscience. 2021;24:660-73. https://doi.org/10.1080/1028415X.2019.1666480
  41. Ibrahim MA, Khalifa AM, Abd El-Fadeal NM, Abdel-Karim RI, Elsharawy AF, Ellawindy A, et al. Alleviation of doxorubicin-induced cardiotoxicity in rat by mesenchymal stem cells and olive leaf extract via MAPK/TNF-? pathway: preclinical, experimental and bioinformatics enrichment study. Tissue Cell. 2023;85:102239. https://doi.org/10.1016/j.tice.2023.102239
  42. Rayat Pisheh H, Sani M. Mesenchymal stem cells derived exosomes: a new era in cardiac regeneration. Stem Cell Research & Therapy. 2025;16:16. https://doi.org/10.1186/s13287-024-04123-2
  43. Sherif IO, Al-Gayyar MMH. Oleuropein potentiates anti-tumor activity of cisplatin against HepG2 through affecting proNGF/NGF balance. Life Sciences. 2018;198:87-93. https://doi.org/10.1016/j.lfs.2018.02.027
  44. Gao S, Zhao Z, Wu R, Zeng Y, Zhang Z, Miao J, et al. Bone marrow mesenchymal stem cell transplantation improves radiation-induced heart injury through DNA damage repair in rat model. Radiation and Environmental Biophysics. 2017;56:63-77. https://doi.org/10.1007/s00411-016-0675-0

Downloads

Download data is not yet available.