The effect of crocin supplementation on glycemic control, insulin resistance and active AMPK levels in patients with type 2 diabetes: a pilot study

Vahideh Behrouz, Ali Dastkhosh, Mehdi Hedayati, Meghdad Sedaghat, Maryam Sharafkhah, Golbon Sohrab, Vahideh Behrouz, Ali Dastkhosh, Mehdi Hedayati, Meghdad Sedaghat, Maryam Sharafkhah, Golbon Sohrab

Abstract

Background: Crocin as a carotenoid exerts anti-oxidant, anti-inflammatory, anti-cancer, neuroprotective and cardioprotective effects. Besides, the increasing prevalence of diabetes mellitus and its allied complications, and also patients' desire to use natural products for treating their diseases, led to the design of this study to evaluate the efficacy of crocin on glycemic control, insulin resistance and active adenosine monophosphate-activated protein kinase (AMPK) levels in patients with type-2 diabetes (T2D).

Methods: In this clinical trial with a parallel-group design, 50 patients with T2D received either 15-mg crocin or placebo, twice daily, for 12 weeks. Anthropometric measurements, dietary intake, physical activity, blood pressure, glucose homeostasis parameters, active form of AMPK were assessed at the beginning and at the end of the study.

Results: Compared with the placebo group, crocin improved fasting glucose level (P = 0.015), hemoglobin A1c (P = 0.045), plasma insulin level (P = 0.046), insulin resistance (P = 0.001), and insulin sensitivity (P = 0.001). Based on the within group analysis, crocin led to significant improvement in plasma levels of glucose, insulin, hemoglobin A1c, systolic blood pressure, insulin resistance and insulin sensitivity. The active form of AMPK did not change within and between groups after intervention.

Conclusions: The findings indicate that crocin supplementation can improve glycemic control and insulin resistance in patients with T2D. Further studies are needed to confirm these findings.Trial Registration This study has been registered at Clinicaltrial.gov with registration number NCT04163757.

Keywords: AMPK; Crocin; Diabete; Glycemic control; Insulin resistance.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interest.

© The Author(s) 2020.

Figures

Fig. 1
Fig. 1
The study consort flowchart
Fig. 2
Fig. 2
Estimated mean percent change of glycemic parameters

References

    1. Vuksan V, Xu ZZ, Jovanovski E, Jenkins AL, Beljan-Zdravkovic U, Sievenpiper JL, et al. Efficacy and safety of American ginseng (Panax quinquefolius L.) extract on glycemic control and cardiovascular risk factors in individuals with type 2 diabetes: a double-blind, randomized, cross-over clinical trial. Eur J Nutr. 2019;58(3):1237–1245.
    1. Wheaton AG, Blanck HM, Gizlice Z, Reyes M. Medicinal herb use in a population-based survey of adults: prevalence and frequency of use, reasons for use, and use among their children. Ann Epidemiol. 2005;15(9):678–685.
    1. Mohan V, John M, Goswami S, Magdam M, Kant S, Vimal M, et al. Precision medicine with sulfonylureas: from clinical studies to bedside practice. J Assoc Phys. 2019;67:27.
    1. Moravej Aleali A, Amani R, Shahbazian H, Namjooyan F, Latifi SM, Cheraghian B. The effect of hydroalcoholic saffron (Crocus sativus L.) extract on fasting plasma glucose, HbA1c, lipid profile, liver, and renal function tests in patients with type 2 diabetes mellitus: a randomized double-blind clinical trial. Phytother Res. 2019;33(6):1648–1657.
    1. Zare R, Nadjarzadeh A, Zarshenas MM, Shams M, Heydari M. Efficacy of cinnamon in patients with type II diabetes mellitus: a randomized controlled clinical trial. Clin Nutr. 2019;38(2):549–556.
    1. Sohrab G, Roshan H, Ebrahimof S, Nikpayam O, Sotoudeh G, Siasi F. Effects of pomegranate juice consumption on blood pressure and lipid profile in patients with type 2 diabetes: a single-blind randomized clinical trial. Clin Nutr ESPEN. 2019;29:30–35.
    1. Yari Z, Movahedian M, Imani H, Alavian SM, Hedayati M, Hekmatdoost A. The effect of hesperidin supplementation on metabolic profiles in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial. Eur J Nutr. 2019 doi: 10.1007/s00394-019-02105-2.
    1. Luo L, Fang K, Dan X, Gu M. Crocin ameliorates hepatic steatosis through activation of AMPK signaling in db/db mice. Lipids Health Dis. 2019;18(1):1–9.
    1. 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.
    1. 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;102:930–937.
    1. Yosri H, Elkashef WF, Said E, Gameil NM. Crocin modulates IL-4/IL-13 signaling and ameliorates experimentally induced allergic airway asthma in a murine model. Int Immunopharmacol. 2017;50:305–312.
    1. Elsherbiny NM, Salama MF, Said E, El-Sherbiny M, Al-Gayyar MM. Crocin protects against doxorubicin-induced myocardial toxicity in rats through down-regulation of inflammatory and apoptic pathways. Chem Biol Interact. 2016;247:39–48.
    1. Rajaei Z, Hosseini M, Alaei H. Efeitos da crocina no dano oxidativo cerebral e na memória aversiva em um modelo 6-OHDA de doença de Parkinson. Arq de Neuro-Neuropsiquiatr. 2016;74(9):723–729.
    1. Samini F, Samarghandian S. Neuroprotective effects of (Crocus Sativus L.) and its main constituents. Der Pharma Lett. 2016;8(13):25–29.
    1. Oruc S, Gönül Y, Tunay K, Oruc OA, Bozkurt MF, Karavelioğlu E, et al. The antioxidant and antiapoptotic effects of crocin pretreatment on global cerebral ischemia reperfusion injury induced by four vessels occlusion in rats. Life Sci. 2016;154:79–86.
    1. Yaribeygi H, Zare V, Butler AE, Barreto GE, Sahebkar A. Antidiabetic potential of saffron and its active constituents. J Cell Physiol. 2019;234(6):8610–8617.
    1. Algandaby MM. Crocin prevents metabolic syndrome in rats via enhancing PPAR-gamma and AMPK. Saudi J Biol Sci. 2020;27(5):1310–1316.
    1. Javandoost A, Afshari A, Nikbakht-Jam I, Khademi M, Eslami S, Nosrati M, et al. Effect of crocin, a carotenoid from saffron, on plasma cholesteryl ester transfer protein and lipid profile in subjects with metabolic syndrome: a double blind randomized clinical trial. ARYA Atheroscler. 2017;13(5):245.
    1. 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):307–312.
    1. Kianbakht S, Hajiaghaee R. Anti-hyperglycemic effects of saffron and its active constituents, crocin and safranal, in alloxan-induced diabetic rats. J Med Plant. 2011;3(39):82–89.
    1. Azimi P, Ghiasvand R, Feizi A, Hosseinzadeh J, Bahreynian M, Hariri M, et al. Effect of cinnamon, cardamom, saffron and ginger consumption on blood pressure and a marker of endothelial function in patients with type 2 diabetes mellitus: a randomized controlled clinical trial. Blood Press. 2016;25(3):133–140.
    1. Roshanravan B, Samarghandian S, Ashrafizadeh M, Amirabadizadeh A, Saeedi F, Farkhondeh T. Metabolic impact of saffron and crocin: an updated systematic and meta-analysis of randomised clinical trials. Arch Physiol Biochem. 2020;1–13.
    1. Rajaei Z, Hadjzadeh M-A-R, 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):206–210.
    1. Shirali S, Zahra Bathaie S, Nakhjavani M. Effect of crocin on the insulin resistance and lipid profile of streptozotocin-induced diabetic rats. Phytother Res. 2013;27(7):1042–1047.
    1. Zhang BB, Zhou G, Li C. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab. 2009;9(5):407–416.
    1. Sharma H, Kumar S. Natural AMPK activators: an alternative approach for the treatment and management of metabolic syndrome. Curr Med Chem. 2017;24(10):1007–1047.
    1. American Diabetes Association 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2019. Diabetes Care. 2019;42(Supplement 1):S13–S28.
    1. Milajerdi A, Jazayeri S, Hashemzadeh N, Shirzadi E, Derakhshan Z, Djazayeri A, et al. 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. 2018;23:16.
    1. Who EC. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet (London, England) 2004;363(9403):157.
    1. WHO . Waist circumference and waist-hip ratio: report of a WHO expert consultation, Geneva, 8-11 December 2008. Geneva: WHO; 2011.
    1. Willett W. Nutritional epidemiology. Oxford: Oxford University Press; 2012.
    1. Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc. 2000;32(9):S498–S516.
    1. Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–419.
    1. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85(7):2402–2410.
    1. 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.
    1. Kang C, Lee H, Jung E-S, Seyedian R, Jo M, Kim J, et al. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms. Food Chem. 2012;135(4):2350–2358.
    1. Xi L, Qian Z, Xu G, Zheng S, Sun S, Wen N, et al. Beneficial impact of crocetin, a carotenoid from saffron, on insulin sensitivity in fructose-fed rats. J Nutr Biochem. 2007;18(1):64–72.
    1. Dehghan F, Hajiaghaalipour F, Yusof A, Muniandy S, Hosseini SA, Heydari S, et al. Saffron with resistance exercise improves diabetic parameters through the GLUT4/AMPK pathway in-vitro and in-vivo. Sci Rep. 2016;6:25139.
    1. Xi L, Qian Z, Shen X, Wen N, Zhang Y. Crocetin prevents dexamethasone-induced insulin resistance in rats. Planta Med. 2005;71(10):917–922.
    1. Ghorbanzadeh V, Mohammadi M, Mohaddes G, Dariushnejad H, Chodari L. Effect of crocin and voluntary exercise on P53 protein in pancreas of type2 diabetic rats. Pharma Sci. 2017;23(3):182–188.
    1. Yaribeygi H, Mohammadi MT, Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomed Pharmacother. 2018;98:333–337.
    1. Sepahi S, Mohajeri SA, Hosseini SM, Khodaverdi E, Shoeibi N, Namdari M, et al. Effects of crocin on diabetic maculopathy: a placebo-controlled randomized clinical trial. Am J Ophthalmol. 2018;190:89–98.
    1. Kermani T, Kazemi T, Molki S, Ilkhani K, Sharifzadeh G, Rajabi O. The efficacy of crocin of saffron (Crocus sativus L.) on the components of metabolic syndrome: a randomized controlled clinical trial. J Res Pharm Pract. 2017;6(4):228.
    1. Gu M, Luo L, Fang K. Crocin inhibits obesity via AMPK-dependent inhibition of adipocyte differentiation and promotion of lipolysis. Biosci Trends. 2018;12(6):587–594.
    1. Fadai F, Mousavi B, Ashtari Z, Farhang S, Hashempour S, Shahhamzei N, et al. Saffron aqueous extract prevents metabolic syndrome in patients with schizophrenia on olanzapine treatment: a randomized triple blind placebo controlled study. Pharmacopsychiatry. 2014;47(04/05):156–161.
    1. Imenshahidi M, Hosseinzadeh H, Javadpour Y. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother Res. 2010;24(7):990–994.
    1. Imenshahidi M, Razavi BM, Faal A, Gholampoor A, Mousavi SM, Hosseinzadeh H. Effects of chronic crocin treatment on desoxycorticosterone acetate (doca)-salt hypertensive rats. Iran J Basic Med Sci. 2014;17(1):9.
    1. Fatehi M, Rashidabady T, Fatehi-Hassanabad Z. Effects of Crocus sativus petals’ extract on rat blood pressure and on responses induced by electrical field stimulation in the rat isolated vas deferens and guinea-pig ileum. J Ethnopharmacol. 2003;84(2–3):199–203.
    1. Razavi B-M, Hosseinzadeh H. Cardiovascular effects of saffron and its active constituents. London: Elsevier; 2020. pp. 451–460.

Source: PubMed

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