Journal of Kerman University of Medical Sciences

Current Issue

By Issue

By Author

Author Index

Keyword Index

About Journal

Aims and Scope

JKMU Ethical Policies

Indexing and Abstracting

Related Links

FAQ

Peer Review Process

News

Metric

Editorial Policies

Data Sharing Policy

The Effect of Saffron and its Active Compounds on Oxidative Stress Markers in Diabetic Rats: A Systematic Review and Meta-analysis of Animal Studies

Document Type : Review Article

Authors

1 Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

2 Department of Clinical Biochemistry, School of Medicine, Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran

3 Department of General Courses, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran

4 Department of Oral and Maxillofacial Surgery, Manipal College of Dental Sciences, Mangalore, Manipal Academy of Higher Education, A Constituent of MAHE, India

5 Department of Community Medicine, Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran

Abstract

Background: Diabetes, as a chronic metabolic disease, can induce oxidative stress, leading to severe damage to various tissues, including the kidneys, heart, and others. This study aimed to assess the influence of saffron and its active component on oxidative stress markers in diabetic rats.
Methods: The databases were searched until December 24, 2021. The quality of the included articles was assessed using SYRCLE’s Risk of Bias tool. To estimate the effects of saffron and its active component, SMD with 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup analysis and meta-regression were used to explore heterogeneity. Publication bias was assessed using the Begg and Egger tests. The results were reported under the PRISMA guidelines.
Results: The meta-analysis comprising 42 articles revealed that prolonged hyperglycemia leads to increased oxidative markers, including malondialdehyde (MDA), nitric oxide (NO), total oxidant status (TOS), xanthine oxidase (XO), and reactive oxygen species (ROS)), and decreased antioxidant defense system, including glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS), thiol groups (SH), and total antioxidant capacity (TAC). Treatment of diabetic rats with saffron, crocin, and safranal decreased the oxidant markers and increased the antioxidant markers.
Conclusion: Saffron, crocin, and safranal reduce oxidative stress by reinforcing the antioxidant defense system and reducing oxidant markers. Hence, we believe that saffron and its active ingredients can be favorable options for managing diabetes and its complications. However, further human studies are required to draw definite conclusions.

Keywords

Main Subjects

References
  1. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4-14. doi: 10.1016/j.diabres.2009.10.007.
  2. Abdul-Hamid M, Moustafa N. Protective effect of curcumin on histopathology and ultrastructure of pancreas in the alloxan treated rats for induction of diabetes. J Basic Appl Zool. 2013;66(4):169-79. doi: 10.1016/j.jobaz.2013.07.003.
  3. Arora MK, Singh UK. Molecular mechanisms in the pathogenesis of diabetic nephropathy: an update. Vascul Pharmacol. 2013;58(4):259-71. doi: 10.1016/j. vph.2013.01.001.
  4. Rains JL, Jain SK. Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med. 2011;50(5):567-75. doi: 10.1016/j.freeradbiomed.2010.12.006.
  5. Zhang P, Li T, Wu X, Nice EC, Huang C, Zhang Y. Oxidative stress and diabetes: antioxidative strategies. Front Med. 2020;14(5):583-600. doi: 10.1007/s11684-019-0729-1.
  6. Kashihara N, Haruna Y, Kondeti VK, Kanwar YS. Oxidative stress in diabetic nephropathy. Curr Med Chem. 2010;17(34):4256-69. doi: 10.2174/092986710793348581.
  7. Yaribeygi H, Sathyapalan T, Atkin SL, Sahebkar A. Molecular mechanisms linking oxidative stress and diabetes mellitus. Oxid Med Cell Longev. 2020;2020:8609213. doi: 10.1155/2020/8609213.
  8. Yaribeygi H, Mohammadi MT, Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomed Pharmacother. 2018;98:333-7. doi: 10.1016/j.biopha.2017.12.077.
  9. Elgazar AF, Rezq AA, Bukhari HM. Anti-hyperglycemic effect of saffron extract in alloxan-induced diabetic rats. Eur J Biol Sci. 2013;5(1):14-22.
  10. Cardone L, Castronuovo D, Perniola M, Cicco N, Candido V. Saffron (Crocus sativus L.), the king of spices: an overview. Sci Hortic. 2020;272:109560. doi: 10.1016/j. scienta.2020.109560.
  11. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4(1):1. doi: 10.1186/2046-4053-4-1.
  12. Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes- Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol. 2014;14:43. doi: 10.1186/1471-2288-14-43.
  13. Faraone SV. Interpreting estimates of treatment effects: implications for managed care. P T. 2008;33(12):700-11.
  14. Mokhayeri Y, Riahi SM, Rahimzadeh S, Pourhoseingholi MA, Hashemi-Nazari SS. Metabolic syndrome prevalence in the Iranian adult’s general population and its trend: a systematic review and meta-analysis of observational studies. Diabetes Metab Syndr. 2018;12(3):441-53. doi: 10.1016/j. dsx.2017.12.023.
  15. Riahi SM, Mokhayeri Y. Methodological issues in a meta-analysis. Curr Med Res Opin. 2017;33(10):1813. doi: 10.1080/03007995.2017.1359152.
  16. Yaribeygi H, Noroozadeh A, Mohammadi MT, Johnston TP, Sahebkar A. Crocin improves oxidative stress by potentiating intrinsic anti-oxidant defense systems in pancreatic cells during uncontrolled hyperglycemia. J Pharmacopuncture. 2019;22(2):83-9. doi: 10.3831/kpi.2019.22.010.
  17. Yaribeygi H, Mohammadi MT, Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomed Pharmacother. 2018;98:333-7. doi: 10.1016/j.biopha.2017.12.077.
  18. Yaribeygi H, Mohammadi MT. Protective Effect of Crocin on Kidney Performance in Chronic Uncontrolled Hyperglycemia- Induced Nephropathy in Rat. J Adv Med Biomed Res. 2017;25(109):36-49. [Persian].
  19. Wu X, Long E, Wang L, Li G, Yang Y, Liu H, et al. Crocin enhances antioxidative and cardioprotective effects of sitagliptin in streptozotocin-induced diabetic rats. Int J Clin Exp Med. 2018;11(7):6848-55.
  20. Talebanzadeh S, Ashrafi M, Kazemipour N, Erjaee H, Nazifi S. Evaluation of the effects of saffron aqueous extract on oxidative stress in the lens of streptozotocin-induced diabetic rats. Biomed Res Ther. 2018;5(4):2133-41. doi: 10.15419/ bmrat.v5i4.427.
  21. Sefidgar SM, Ahmadi-Hamedani M, Jebelli Javan A, Narenji Sani R, Javaheri Vayghan A. Effect of crocin on biochemical parameters, oxidative/antioxidative profiles, sperm characteristics and testicular histopathology in streptozotocin-induced diabetic rats. Avicenna J Phytomed. 2019;9(4):347-61.
  22. Samarghandian S, Borji A, Delkhosh MB, Samini F. Safranal treatment improves hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats. J Pharm Pharm Sci. 2013;16(2):352-62. doi: 10.18433/j3zs3q.
  23. Samarghandian S, Azimi-Nezhad M, Samini F. Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced experimental diabetes mellitus. Biomed Res Int. 2014;2014:920857. doi: 10.1155/2014/920857.
  24. Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats. Indian Heart J. 2017;69(2):151-9. doi: 10.1016/j. ihj.2016.09.008.
  25. Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Crocin attenuate tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in streptozotocin-induced diabetic rat aorta. Cytokine. 2016;88:20-8. doi: 10.1016/j.cyto.2016.08.002.
  26. Samarghandian S, Afshari R, Sadati A. Evaluation of lung and bronchoalveolar lavage fluid oxidative stress indices for assessing the preventing effects of safranal on respiratory distress in diabetic rats. ScientificWorldJournal. 2014;2014:251378. doi: 10.1155/2014/251378.
  27. Samaha MM, Said E, Salem HA. A comparative study of the role of crocin and sitagliptin in attenuation of STZ-induced diabetes mellitus and the associated inflammatory and apoptotic changes in pancreatic β-islets. Environ Toxicol Pharmacol. 2019;72:103238. doi: 10.1016/j.etap.2019.103238.
  28. Rajaei Z, Hadjzadeh MA, Nemati H, Hosseini M, Ahmadi M, Shafiee S. Antihyperglycemic and antioxidant activity of crocin in streptozotocin-induced diabetic rats. J Med Food. 2013;16(3):206-10. doi: 10.1089/jmf.2012.2407.
  29. Rahbani M, Mohajeri D, Rezaie A, Nazeri M. Protective effect of ethanolic extract of saffron (dried stigmas of Crocus sativus L.) on hepatic tissue injury in streptozotocin-induced diabetic rats. J Anim Vet Adv. 2012;11(12):1985-94. doi: 10.3923/ javaa.2012.1985.1994.
  30. Qiu Y, Jiang X, Liu D, Deng Z, Hu W, Li Z, et al. The hypoglycemic and renal protection properties of crocin via oxidative stress-regulated NF-κB signaling in db/db mice. Front Pharmacol. 2020;11:541. doi: 10.3389/fphar.2020.00541.
  31. Motamedrad M, Shokouhifar A, Hemmati M, Moossavi M. The regulatory effect of saffron stigma on the gene expression of the glucose metabolism key enzymes and stress proteins in streptozotocin-induced diabetic rats. Res Pharm Sci. 2019;14(3):255-62. doi: 10.4103/1735-5362.258494.
  32. Rahbani M, Mohajeri D, Rezaie A, Doustar Y, Nazeri M. Attenuation of oxidative stress of hepatic tissue by ethanolic extract of saffron (dried stigmas of Crocus sativus L.) in streptozotocin (STZ)-induced diabetic rats. Afr J Pharm Pharmacol. 2011;5(19):2166-73. doi: 10.5897/ajpp11.624.
  33. Margaritis I, Angelopoulou K, Lavrentiadou S, Mavrovouniotis IC, Tsantarliotou M, Taitzoglou I, et al. Effect of crocin on antioxidant gene expression, fibrinolytic parameters, redox status and blood biochemistry in nicotinamide-streptozotocin-induced diabetic rats. J Biol Res (Thessalon). 2020;27:4. doi: 10.1186/s40709-020-00114-5.
  34. Kianbakht S, Mozafari K. Effects of saffron and its active constituents, crocin and safranal, on prevention of indomethacin induced gastric ulcers in diabetic and nondiabetic rats. J Med Plants. 2009;8(Suppl 5):30-8.
  35. Hazman Ö, Ovalı S. Investigation of the anti-inflammatory effects of safranal on high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Inflammation. 2015;38(3):1012-9. doi: 10.1007/s10753-014- 0065-1.
  36. Hazman Ö, Bozkurt MF. Anti-inflammatory and antioxidative activities of safranal in the reduction of renal dysfunction and damage that occur in diabetic nephropathy. Inflammation. 2015;38(4):1537-45. doi: 10.1007/s10753-015-0128-y.
  37. Hazman Ö, Aksoy L, Büyükben A. Effects of crocin on experimental obesity and type-2 diabetes. Turk J Med Sci. 2016;46(5):1593-602. doi: 10.3906/sag-1506-108.
  38. Hasanpour M, Ashrafi M, Erjaee H, Nazifi S. The effect of saffron aqueous extract on oxidative stress parameters and important biochemical enzymes in the testis of streptozotocin-induced diabetic rats. Physiol Pharmacol. 2018;22(1):28-37.
  39. Yaribeygi H, Mohammadi MT, Rezaee R, Sahebkar A. Crocin improves renal function by declining Nox-4, IL-18, and p53 expression levels in an experimental model of diabetic nephropathy. J Cell Biochem. 2018;119(7):6080-93. doi: 10.1002/jcb.26806.
  40. Ghorbanzadeh V, Mohammadi M, Mohaddes G, Dariushnejad H, Chodari L, Mohammadi S. Protective effect of crocin and voluntary exercise against oxidative stress in the heart of high-fat diet-induced type 2 diabetic rats. Physiol Int. 2016;103(4):459-68. doi: 10.1556/2060.103.2016.4.6.
  41. Farshid AA, Tamaddonfard E, Moradi-Arzeloo M, Mirzakhani N. The effects of crocin, insulin and their co-administration on the heart function and pathology in streptozotocin-induced diabetic rats. Avicenna J Phytomed. 2016;6(6):658-70.
  42. Farshid AA, Tamaddonfard E. Histopathological and behavioral evaluations of the effects of crocin, safranal and insulin on diabetic peripheral neuropathy in rats. Avicenna J Phytomed. 2015;5(5):469-78.
  43. El-Fawal R, El Fayoumi HM, Mahmoud MF. Diosmin and crocin alleviate nephropathy in metabolic syndrome rat model: effect on oxidative stress and low-grade inflammation. Biomed Pharmacother. 2018;102:930-7. doi: 10.1016/j. biopha.2018.03.162.
  44. Bajerska J, Mildner-Szkudlarz S, Podgórski T, Oszmatek- Pruszyńska E. Saffron (Crocus sativus L.) powder as an ingredient of rye bread: an anti-diabetic evaluation. J Med Food. 2013;16(9):847-56. doi: 10.1089/jmf.2012.0168.
  45. Bahmani F, Bathaie SZ, Aldavood SJ, Ghahghaei A. Inhibitory effect of crocin(s) on lens α-crystallin glycation and aggregation, results in the decrease of the risk of diabetic cataract. Molecules. 2016;21(2):143. doi: 10.3390/ molecules21020143.
  46. Asri-Rezaei S, Tamaddonfard E, Ghasemsoltani-Momtaz B, Erfanparast A, Gholamalipour S. Effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in streptozotocin-induced diabetic rats. Avicenna J Phytomed. 2015;5(5):403-12.
  47. Ashrafi M, Nazifi S, Namazi F, Kazemipour N, Karimi B, Goudarzi T, et al. Renal protective effect of saffron aqueous extract in streptozotocin induced diabetic rats. Int J Med Res Health Sci. 2017;6(9):151-61.
  48. Altinoz E, Taskin E, Oner Z, Elbe H, Arslan BA. The effect of saffron (its active constituent, crocin) on the cardiovascular complication and dyslipidemia in streptozotocin induced diabetic rats. Afr J Tradit Complement Altern Med. 2015;12(5):1-7. doi: 10.4314/ajtcam.v12i5.1.
  49. Altinzo E, Oner Z, Elbe H, Vardi N. Neuro-protective effects of crocin on brain and cerebellum tissues in diabetic rats. Afr J Tradit Complement Altern Med. 2014;11(6):33-9. doi: 10.4314/ajtcam.v11i6.2.
  50. Altinoz E, Oner Z, Elbe H, Cigremis Y, Turkoz Y. Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats. Hum Exp Toxicol. 2015;34(2):127-34. doi: 10.1177/0960327114538989.
  51. Ahmadi M, Rajaei Z, Hadjzadeh MA, Nemati H, Hosseini M. Crocin improves spatial learning and memory deficits in the Morris water maze via attenuating cortical oxidative damage in diabetic rats. Neurosci Lett. 2017;642:1-6. doi: 10.1016/j. neulet.2017.01.049.
  52. Abou-Hany HO, Atef H, Said E, Elkashef HA, Salem HA. Crocin mediated amelioration of oxidative burden and inflammatory cascade suppresses diabetic nephropathy progression in diabetic rats. Chem Biol Interact. 2018;284:90- 100. doi: 10.1016/j.cbi.2018.02.001.
  53. Tamaddonfard E, Farshid AA, Asri-Rezaee S, Javadi S, Khosravi V, Rahman B, et al. Crocin improved learning and memory impairments in streptozotocin-induced diabetic rats. Iran J Basic Med Sci. 2013;16(1):91-100.
  54. Altinoz E, Oner Z, Elbe H, Turkoz Y, Cigremis Y. Protective effect of saffron (its active constituent, crocin) on oxidative stress and hepatic injury in streptozotocin induced diabetic rats. Gene Ther Mol Biol. 2014;16(1):160-71.
  55. Kapucu A. Crocin ameliorates oxidative stress and suppresses renal damage in streptozotocin induced diabetic male rats. Biotech Histochem. 2021;96(2):153-60. doi: 10.1080/10520295.2020.1808702.
  56. Skourtis G, Krontira A, Ntaoula S, Ferlemi AV, Zeliou K, Georgakopoulos C, et al. Protective antioxidant effects of saffron extract on retinas of streptozotocin-induced diabetic rats. Rom J Ophthalmol. 2020;64(4):394-403. doi: 10.22336/ rjo.2020.61.
  57. Yaribeygi H, Atkin SL, Barreto GE, Sahebkar A. Crocin improves oxidative stress in testicular tissues of streptozotocin-induced diabetic rats. Adv Exp Med Biol. 2021;1308:273-81. doi: 10.1007/978-3-030-64872-5_19.
  58. Yaribeygi H, Zare V, Butler AE, Barreto GE, Sahebkar A. Antidiabetic potential of saffron and its active constituents. J Cell Physiol. 2019;234(6):8610-7. doi: 10.1002/jcp.27843.
  59. Matough FA, Budin SB, Hamid ZA, Alwahaibi N, Mohamed J. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos Univ Med J. 2012;12(1):5-18. doi: 10.12816/0003082.
  60. Caballero-Ortega H, Pereda-Miranda R, Abdullaev FI. HPLC quantification of major active components from 11 different saffron (Crocus sativus L.) sources. Food Chem. 2007;100(3):1126-31. doi: 10.1016/j.foodchem.2005.11.020.
  61. Hosseinzadeh H, Modaghegh MH, Saffari Z. Crocus sativus L. (saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle. Evid Based Complement Alternat Med. 2009;6(3):343-50. doi: 10.1093/ecam/nem125.
Journal of Kerman University of Medical Sciences
Volume 31, Issue 4
July and August 2024
Pages 214-225
Files
Share
How to cite
Statistics