Document Type : Original Article(s)
- Ali Javandoost 1
- Asma Afshari 2
- Irandokht Nikbakht-Jam 1
- Mohammad Khademi 3
- Saied Eslami 4
- Mina Nosrati 5
- Mojtaba Foroutan-Tanha 6
- Amirhossein Sahebkar 7
- Shima Tavalaie 5
- Majid Ghayour-Mobarhan 8
- Gordon Ferns 9
- Farzin Hadizadeh 10
- Abolghasem Tabassi 11
- Ahmad Mohajeri 12
1 Metabolic Syndrome Research Center AND School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2 Assistant Professor, Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3 PhD Candidate, Student Research Committee, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
4 Professor, Pharmaceutical Research Center AND School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
5 Biochemistry and Nutrition Research Center AND School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
6 Metabolic Syndrome Research Center AND Cardiovascular Research Center AND School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
7 Associate Professor, Department of Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
8 Professor, Cardiovascular Research Center AND Metabolic Syndrome Research Center AND School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
9 School of Brighton and Sussex Medical, Division of Medical Education, Mayfield House, University of Brighton, Brighton, UK
10 Professor, Biotechnology Research Center AND School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
11 Pharmacological Research Center of Medicinal Plants AND School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
12 Associate Professor, Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
BACKGROUND: Metabolic syndrome is defined by insulin resistance and a clustering of other cardiovascular risk factors. Crocin is a carotenoid derived from the stigmas of the saffron flower and had previously been shown to affect lipid profile. However, the mechanism for this function is not well understood. The present trial aimed to investigate the possible effect of crocin on plasma levels of cholesteryl ester transfer protein and lipid profile in individuals with metabolic syndrome. METHODS: This was a randomized, double-blind, placebo-controlled, clinical trial consisting of an 8-week treatment with crocin, or placebo tablets between April and June 2014, in the Nutrition Clinic of Ghaem Teaching Hospital, Mashhad, Iran. Participants were randomly assigned to take a 30 mg/day crocin (n = 22) in the intervention group or placebo (n = 22) in the control group. Anthropometric, hematological and biochemical parameters were measured and recorded during pre and post-treatment periods. RESULTS: Whilst plasma cholesteryl ester transfer protein was increased in the group taking the crocin tablet by 27.81% during the trial period (P = 0.013), the difference between the crocin and placebo groups was not significant (P = 0.116). Moreover, the percent changes in cholesterol (P = 0.702), triglyceride (P = 0.080), low-density lipoprotein (LDL) (P = 0.986), high-density lipoprotein (HDL) (P = 0.687) and fasting blood glucose (P = 0.614) did not differ significantly between intervention and control groups. CONCLUSION: Although crocin supplements increased the serum cholesteryl ester transfer protein in patients with metabolic syndrome, this change was not significant between treatment and placebo groups.
- Inazu A, Brown ML, Hesler CB, Agellon LB, Koizumi J, Takata K, et al. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med 1990; 323(18): 1234-8.
- Barter PJ, Kastelein JJ. Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J Am Coll Cardiol 2006; 47(3): 492-9.
- Al-Daghri NM, Al-Attas O, Patel A, Belyaev ND, Bartlett WA, Jones AF, et al. Association between the cholesteryl ester transfer protein TaqI-detectable B polymorphism and low high-density lipoprotein cholesterol concentration in Saudis. Clin Sci 2003; 105(4): 467-72.
- Abdullaev FI. Biological effects of saffron. Biofactors 1993; 4(2): 83-6.
- Melnyk JP, Wang S, Marcone MF. Chemical and biological properties of the world's most expensive spice: Saffron. Food Res Int 2010; 43(8): 1981-9.
- Duke JA. Handbook of phytochemical constituent grass, herbs and other economic plants. Boca Raton, FL: CRC Press; 1992.
- Soeda S, Ochiai T, Shimeno H, Saito H, Abe K, Tanaka H, et al. Pharmacological activities of crocin in saffron. J Nat Med 2007; 61(2): 102-11.
- Abe K, Saito H. Effects of saffron extract and its constituent crocin on learning behaviour and long-term potentiation. Phytother Res 2000; 14(3): 149-52.
- Fernandez JA. Anticancer properties of saffron, Crocus sativus Linn. In: Khan MTH, Ather A, Editors. Advances in phytomedicine lead molecules from natural products. 2 ed. Elsevier; 2006. p. 313-30.
- Konoshima T, Tokuda H, Morimoto S, Tanaka H, Kawata E, Xuan EL, et al. Crocin and crocetin derivatives inhibit skin tumour promotion in mice. Phytother Res 1998; 12(6): 400-4.
- Kianbakht S, Mozaffari 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(3): 30-8.
- Assimopoulou AN, Sinakos Z, Papageorgiou VP. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res 2005; 19(11): 997-1000.
- Hosseinzadeh H, Sadeghnia HR, Ziaee T, Danaee A. 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 2005; 8(3): 387-93.
- Shen XC, Qian ZY. Effects of crocetin on antioxidant enzymatic activities in cardiac hypertrophy induced by norepinephrine in rats. Pharmazie 2006; 61(4): 348-52.
- Hariri AT, Moallem SA, Mahmoudi M, Memar B, Hosseinzadeh H. Sub-acute effects of diazinon on biochemical indices and specific biomarkers in rats: Protective effects of crocin and safranal. Food Chem Toxicol 2010; 48(10): 2803-8.
- Lopez-Rios L, Novoa FJ, Chirino R, Varillas F, Boronat-Cortes M, Wagner AM. Interaction between cholesteryl ester transfer protein and hepatic lipase encoding genes and the risk of type 2 diabetes: results from the Telde study. PLoS One 2011; 6(11): e27208.
- Sirdah MM, Al Laham NA, Abu Ghali AS. Prevalence of metabolic syndrome and associated socioeconomic and demographic factors among Palestinian adults (20-65 years) at the Gaza Strip. Diabetes Metab Syndr 2011; 5(2): 93-7.
- Yousefzadeh G, Shokoohi M, Najafipour H, Shadkamfarokhi M. applying the framingham risk score for prediction of metabolic syndrome: The Kerman coronary artery disease risk study, Iran. ARYA Atheroscler 2015; 11(3): 179-85.
- Sandhofer A, Tatarczyk T, Laimer M, Ritsch A, Kaser S, Paulweber B, et al. The Taq1B-variant in the cholesteryl ester-transfer protein gene and the risk of metabolic syndrome. Obesity (Silver Spring) 2008; 16(4): 919-22.
- Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001; 285(19): 2486-97.
- Nikbakht-Jam I, Khademi M, Nosrati M, Eslami S, Foroutan-Tanha M, Sahebkar A, et al. Effect of crocin extracted from saffron on pro-oxidant-anti-oxidant balance in subjects with metabolic syndrome: A randomized, placebo-controlled clinical trial. Eur J Integr Med 2016; 8(3): 307-12.
- Talaei A, Hassanpour Moghadam M, Sajadi Tabassi SA, Mohajeri SA. Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: A randomized, double-blind, placebo-controlled, pilot clinical trial. J Affect Disord 2015; 174: 51-6.
- Hadizadeh F, Mohajeri SA, Seifi M. Extraction and purification of crocin from saffron stigmas employing a simple and efficient crystallization method. Pak J Biol Sci 2010; 13(14): 691-8.
- Mohammadian-Hafshejani A, Sarrafzadegan N, Sadeghi M. Some facts about the Metabolic Syndrome in Iran. ARYA Atheroscler 2017; 13(2): 95-6.
- Wong ND. Intensified screening and treatment of the metabolic syndrome for cardiovascular risk reduction. Prev Cardiol 2005; 8(1): 47-52.
- Masson D, Jiang XC, Lagrost L, Tall AR. The role of plasma lipid transfer proteins in lipoprotein metabolism and atherogenesis. J Lipid Res 2009; 50(Suppl): S201-S206.
- Mohamadian M, Goodarzi MT, Saidijam M, Karimi J, Borzouei S, Soltanian A, et al. TAQ 1B polymorphism in cholesterol ester transfer protein and its association with metabolic syndrome parameters. J Urmia Univ Med Sci 2015; 25(11): 1041-9. [In Persian].
- Clark RW, Ruggeri RB, Cunningham D, Bamberger MJ. Description of the torcetrapib series of cholesteryl ester transfer protein inhibitors, including mechanism of action. J Lipid Res 2006; 47(3): 537-52.
- Schwartz GG, Olsson AG, Ballantyne CM, Barter PJ, Holme IM, Kallend D, et al. Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. Am Heart J 2009; 158(6): 896-901.
- Krishna R, Anderson MS, Bergman AJ, Jin B, Fallon M, Cote J, et al. Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: Two double-blind, randomised placebo-controlled phase I studies. Lancet 2007;
- (9603): 1907-14.
- Mohammadpour AH, Akhlaghi F. Future of cholesteryl ester transfer protein (CETP) inhibitors: A pharmacological perspective. Clin Pharmacokinet 2013; 52(8): 615-26.
- Sheng L, Qian Z, Zheng S, Xi L. Mechanism of hypolipidemic effect of crocin in rats: Crocin inhibits pancreatic lipase. Eur J Pharmacol 2006; 543(1-3): 116-22.
- Foger B, Ritsch A, Doblinger A, Wessels H, Patsch JR. Relationship of plasma cholesteryl ester transfer protein to H DL cholesterol. Studies in normotriglyceridemia and moderate hypertriglyceridemia. Arterioscler Thromb Vasc Biol 1996; 16(12): 1430-6.
- Sandhofer A, Kaser S, Ritsch A, Laimer M, Engl J, Paulweber B, et al. Cholesteryl ester transfer protein in metabolic syndrome. Obesity (Silver Spring) 2006; 14(5): 812-8.