Effects of saffron on homocysteine, and antioxidant and inflammatory biomarkers levels in patients with type 2 diabetes mellitus: a randomized double-blind clinical trial

Document Type : Original Research Article


1 Diabetes Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

2 Department of Clinical Nutrition, School of Nutrition & Food Science, Food security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

3 Department of Pharmacognosy, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

4 Department of Epidemiology & Biostatistics, School of Public Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

5 Aerosol Research Laboratory, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

6 Cellular and molecular research center, Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.


Objective: Type 2 diabetes mellitus (T2DM) is one of the most common health problems worldwide. Studies have shown that saffron and its derivatives may have therapeutic potentials in T2DM through reducing plasma glucose. The present study aimed to evaluate the effects of saffron extract on serum anti-inflammatory and antioxidant variables in T2DM patients.
Materials and Methods: This was a double-blind randomized clinical trial conducted on 64 T2DM patients. Participants received either 15 mg of saffron or placebo capsules (two pills per day) for 3 months Anthropometric indices, homocysteine, serum anti-inflammatory and antioxidant variables and dietary intake were assessed pre- and post-intervention.
Results: After 3 months of treatment, interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) increased significantly in both group (p<0.05). No significant differences were observed for total antioxidant capacity (TAC), malondialdehyde (MDA),highsensitivity C-reactive protein (hs-CRP) and interleukin 10(IL-10) after the treatment period (p>0.05). Homocysteine decteased significantly in control group (p<0.05).
Conclusion: Our results showed no improvement in homocystein levels, antioxidant status and inflammatory biomarkers in T2DM patients after treatment with saffron.


Main Subjects

Abbasnezhad A, Hayatdavoudi P, Niazmand S. Mahmoudabady M. 2015. The effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in hippocampus of STZ-induced diabetic rats. Avicenna Jphytomed, 5: 333-340
Aghamohammadi V, Pourghassem GargarI B. Aliasgharzadeh A. 2011. Evaluation of the level of plasma homocysteine in patients with type 2 diabetes mellitus under metformin treatment and its correlation with serum total antioxidant capacity, malondialdehyde, creatinine, insulin resistance and glycemic control. ZUMS J, 19: 1-10.
Ahangarpour A, Heidari H, Oroojan AA, Mirzavandi F, Esfehani KN, Mohammadi ZD. 2017. Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root’s hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice. Avicenna J Phytom, 7: 169-179.
Akhondzadeh S, Sabet MS, Harirchian M, Togha M, Cheraghmakani H, Razeghi S, Hejazi SS, Yousefi M, Alimardani R, Jamshidi A. 2010. Saffron in the treatment of patients with mild to moderate Alzheimer’s disease: a 16‐week, randomized and placebo‐controlled trial. J Clin Pham Ther, 35: 581-588.
Azimi P, Ghiasvand R, Feizi A, Hariri M.  Abbasi B. 2014. Effects of cinnamon, cardamom, saffron, and ginger consumption on markers of glycemic control, lipid profile, oxidative stress, and inflammation in Type 2 diabetes patients. Rev Diabet Stud, 11: 258-266.
Beji RS, Khemir S, Wannes WA, Ayari K, Ksouri R. 2018. Antidiabetic, antihyperlipidemic and antioxidant influences of the spice cinnamon (Cinnamomum zeylanicumon) in experimental rats. Braz J Pharm Sci, 54:1-8.
Bharti S, Golechha M, Kumari S, Siddiqui, KM, Arya DS. 2012. Akt/GSK-3beta/eNOS phosphorylation arbitrates safranal-induced myocardial protection against ischemia-reperfusion injury in rats. Eur J Nutr,51:719-727.
 Bolhassani A, Khavari A. Bathaie S. 2014. Saffron and natural carotenoids: Biochemical activities and anti-tumor effects. Biochim Biophys Acta, 1845:20-30.
Fadai F, Mousavi B, Ashtari Z, Farhang S, Hashempour S, Shahhamzei N, Bathaie SZ. 2014. Saffron aqueous extract prevents metabolic syndrome in patients with schizophrenia on olanzapine treatment: a randomized triple blind placebo controlled study. Pharmacopsychiatry, 47: 156-161.
Farkhondeh T, Samarghandian S. 2014. The effect of saffron (Crocus sativus L.) and its ingredients on the management of diabetes mellitus and dislipidemia. Afr J Pharm Pharmacol, 8:541-549.
Ghorbani A. 2013. Best herbs for managing diabetes: A review of clinical studies. Braz J Pharm, 49:413-422.
Gilbert MP, Pratley RE. 2009. Efficacy and safety of incretin-based therapies in patients with type 2 diabetes mellitus. Am J Med, 122: S11-24.
Hemmati M, Zohoori E, Mehrpour O, Karamian M, Asghari S, Zarban A, Nasouti R. 2015. Anti-atherogenic potential of jujube, saffron and barberry: anti-diabetic and antioxidant actions. Excli J, 14: 908-915.
Hosseini A, Shafiee-nick R, Ghorbani A. 2015. Pancreatic beta cell protection/regeneration with phytotherapy. Braz J Pharm, 51: 1-16.
Hosseinzadeh H, Modaghegh MH, Saffari Z. 2009. Crocus sativus L. (Saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle. Evid Based Complement Alternat Med, 6: 343-350.
Hosseinzadeh H, Sadeghnia HR. 2005. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci, 8: 394-399.
Hosseinzadeh H, Sadeghnia HR, Ziaee T, Danaee A. 2005. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion-induced oxidative damage in rats. J Pharm Pharm Sci, 8: 387-393.
Jelodar G, Javid Z, Sahraian A, Jelodar S. 2018. Saffron improved depression and reduced homocysteine level in patients with major depression: A Randomized, double-blind study. Avicenna J Phytomed, 8: 43-50.
Kianbakht S, Hagiaghaee R. 2011. Anti-hyperglycemic effects of saffron and its active constituents, crocin and safranal, in alloxan-induced diabetic rats. J Med Plant, 3: 82-89.
Makhlouf H, Saksouk M, Habib J, Chahine R. 2011. Determination of antioxidant activity of saffron taken from the flower of Crocus sativus grown in Lebanon. Afr J Biotechnol, 10: 8093-8100.
Maleki-saghooni N, Mirzaeii K, Hosseinzadeh H, Sadeghi R, Irani M. 2018. A systematic review and meta-analysis of clinical trials on saffron (Crocus sativus) effectiveness and safety on erectile dysfunction and semen parameters. Avicenna J Phytomed, 8: 198-209.
Mard SA, Nikraftar Z, Farbood Y, Mansouri E. 2015. A preliminary study of the anti-inflammatory and anti-apoptotic effects of crocin against gastric ischemia-reperfusion injury in rats. Braz J Pharm, 51: 637-642.
Milajerdi A, Djazayeri A, Jazayeri S, Hashemzadeh N, Shirzadi E, Derakhshan Z, Akhondzadeh S. 2016. The effect of hydro-alcoholic extract of saffron stigma (crocus sativus l.) on metabolic control parameters, liver enzymes, and renal function parameters in type 2 diabetic patients. J Med Plant, 4:142-151.
Milajerdi A, Jazayeri S, Hashemzadeh N, Shirzadi E, Derakhshan Z, Djazayeri A, Akhondzadeh S. 2018. The effect of saffron (Crocus sativus L.) hydroalcoholic extract on metabolic control in type 2 diabetes mellitus: A triple-blinded randomized clinical trial. J Res Med Sci, 23:16- 22.
Mohamadpour AH, Ayati Z, Parizadeh MR, Rajbai O, Hosseinzadeh H. 2013. Safety evaluation of crocin(a constituent of saffron) tablets in healthy volunteers. Iran J Basic Med Sci, 16: 39–46.
Mohammad R, Daryoush M, Ali R, Yousef D, Mehrdad N. 2011. 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, 5:2166-2173.
Moller DE. 2000. Potential role of TNF-α in the pathogenesis of insulin resistance and type 2 diabetes. TEM, 11: 212-217.
Rezaee R, Hosseinzadeh H. 2013. Safranal: from an aromatic natural product to a rewarding pharmacological agent. Iran J Basic Med Sci, 16: 12-26.
Riahi-zanjani B, Balali-mood M, Mohammadi E, Badie-bostan H, Memar B, Karimi G. 2015. Safranal as a safe compound to mice immune system. Avicenna J Phytomed, 5:441-449.
Samarghandian S, Azimi-nezhad M, Samini F. 2014. Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced experimental diabetes mellitus. Biomed Res Int, 2014:1-12.
Samarghandian S, Borji A, Delkhosh MB, Samini F. 2013. Safranal treatment improves hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats. J Pharm Pharm Sci, 16:352-362.
Saxena M, Srivastava N, Banerjee M. 2013. Association of IL-6, TNF-alpha and IL-10 gene polymorphisms with type 2 diabetes mellitus. Mol Biol Rep, 40:6271-6279.
Wani BA, Hamza AKR, Mohiddin F. 2011. Saffron: A repository of medicinal properties. J Med Plant Res, 5: 2131-2135.
Yazdanpanah L, Shahbazian H, Aleali AM, Jahanshahi A, Ghanbari S, Latifi S. 2016. Prevalence, awareness and risk factors of diabetes in Ahvaz (South West of Iran). Diabetes Metab Syndr, 10: S114-S118.