The Protective Role of Crocus Sativus L. (Saffron) Against Ischemia- Reperfusion Injury, Hyperlipidemia and Atherosclerosis: Nature Opposing Cardiovascular Diseases

Abstract

Literature findings represented in current review herald promising results for using Crocus Sativus L. and/or its active constituents as a cardiovascular-protective agent and in particular, Crocus Sativus L. manifests beneficial results against ischemia-reperfusion injury, hypertension, hyperlipidemia and diabetes.

Antidiabetic potential of saffron and its active constituents

“…The active ingredients of saffron are able to exert antioxidant (Nikbakht‐Jam et al, ; Rahiman, Akaberi, Sahebkar, Emami, & Tayarani‐Najaran, ; Yaribeygi, Mohammadi, Rezaee, & Sahebkar, ), anti‐inflammatory (Yaribeygi, Mohammadi, Rezaee, et al, ), memory enhancer (Abe & Saito, ; Ghadrdoost et al, ), antitumor (Hoshyar & Mollaei, ; Moradzadeh, Sadeghnia, Tabarraei, & Sahebkar, ), antidepressant (Jam et al, ; Lopresti & Drummond, ; Shafiee, Arekhi, Omranzadeh, & Sahebkar, ), antiasthma (Javadi, Sahebkar, & Emami, ), cough suppressant (El‐Alfy, ), cardiovascular protection (Hatziagapiou & Lambrou, ; Sobhani, Nami, Emami, Sahebkar, & Javadi, ), neuroprotection (Wang et al, ), visual function improvement (Liou et al, ; Riazi et al, ) and sexual behavior potentiation effects (Malviya, Malviya, Jain, & Vyas, ; Sadoughi, ; Table ). This evidence implies that the active compounds of saffron can alter molecular mechanisms by affecting transcription factors, growth factors and diverse intracellular signaling pathways (Samarghandian, Azimi‐Nezhad, & Farkhondeh, ; Yang et al, ; Yaribeygi, Mohammadi, Rezaee, et al, ).…”

“…Finally, the evidence links caspases with β-cell destruction and islet failure(Liadis et al, 2005). Caspases are a family of proteins involved in various forms of cellular death, such asT A B L E 2 Hypoglycemic effects of saffron ingredients by improvement of insulin signaling via phosphorylation of AMPK/ACC; induction of the GLUT4/AMPK molecular pathway, downregulation of adiponectin and TNF-α, lowering of free fatty acids and triglycerides and improvement in the plasma lipid profile, prevention of oxidative stress, inhibition of PTP1B Dehghan et al (2016), Hazman et al (2016), Kang et al (2012), Xi et al (2005), Xi, Qian, Xu, Zheng, et al (2007), Xi, Qian, Xu, Zho, et al (2007), and Yaribeygi, Katsiki, et al (2018) Improvement in β-cell function Prevention of β-cell damage by inhibition of injurious pathways such as oxidative stress and inflammation, suppression of caspase-dependent β-cell damage, downregulation of p53 that is involved in β-cell apoptosis Brownlee (2003), Elgazar et al (2013), Elsherbiny et al (2016), Ghorbanzadeh et al (2017), Keane et al (2015), Liadis et al (2005), Lv et al (2016), and Zhang et al (2015)Induction of GLUT4 expression/localizationInduction of GLUT4 translocation into the plasma membrane by AMPK/ACC and Akt kinase pathways as well as by insulin secretionDu et al (2018),Hazman et al (2016),Maeda et al (2014),Shirali et al (2013),and Yaribeygi, Katsiki, et al (2018) Prevention of oxidative stress Protection against oxidative stress-induced diabetes by potentiation of antioxidant elements and free radical scavengingHatziagapiou and Lambrou (2018),Hu et al (2018),Kianbakht and Hajiaghaee (2011), Maritim et al (2003),Yang et al (2017),Yaribeygi, Faghihi, et al (2018),…”

“…demonstrated that saffron markedly increased peripheral insulin sensitivity by phosphorylation of acetyl-CoA carboxylase (AMPK/ACC) and mitogen-activated protein kinases, but not PI3-kinase/Akt Xi, Qian, Xu, Zheng, et al (2007). demonstrated that T A B L E 1 Beneficial effects of saffron nutraceuticals Classes of effects Details of effects References Saffron ingredient effects Antioxidant Prevention of oxidative stress by potentiation of antioxidative defenses, free radical scavenging Yaribeygi, Mohammadi, and Sahebkar (2018) Antidiabetes Hypoglycemic effects by increasing insulin sensitivity, β-cell function and improvement in insulin signal transduction Shirali et al (2013) and Xi, Qian, Xu, Zho, et al Prevention of inflammatory mediator expression and inhibition of inflammatory responses Cardiovascular protection Protection of the cardiovascular system from atherosclerosis and improvement of endothelial functionHatziagapiou and Lambrou (2018) Antitumor Suppression of malignant cells by induction of apoptosisHoshyar and Mollaei (2017) crocetin therapy in diabetic rats improved insulin sensitivity by downregulation of adiponectin, tumor necrosis factor-α (TNF-α) and leptin expression in white adipocytes at both the protein and messenger RNA (mRNA) level. They also reported that crocetin prevented dexamethasone-induced insulin resistance by lowering free fatty acids and triglycerides in plasma and by downregulation of TNF-α(Xi, Qian, Shen, Wen, & Zhang, 2005).…”

Inhibitory effects of four active components in saffron on human ether-a-go-go-related gene (hERG) K+ currents

“…Crocus sativus L. (saffron) is a perennial herb and has been used for medicinal purposes for many centuries (Bathaie and Mousavi 2010;Bukhari et al 2018). It is of great value for changing the color and flavor of a variety of foods and drinks and has been widely used in medicine to treat several illnesses, including cardiovascular diseases (Razavi and Hosseinzadeh 2017;Hatziagapiou and Lambrou 2018).…”

Inflammatory markers response to crocin supplementation in patients with type 2 diabetes mellitus: A randomized controlled trial

“…Saffran's antioxidant activities could be attributed to its phenolic and flavonoid compounds; gallic acid and pyrogallol are known as the major phenolic and flavonoid components, respectively. Phenolic and flavonoids are highly effective scavengers in neutralizing oxidizing molecules (Hatziagapiou & Lambrou, 2018).…”