Saffron ( Crocus sativus ) intake provides nutritional preconditioning against myocardial ischemia–reperfusion injury in Wild Type and ApoE (−/−) mice: Involvement of Nrf2 activation

Efentakis, Panagiotis; Rizakou, A.; Christodoulou, Eirini; Chatzianastasiou, Athanasia; López, Manuela G.; León, Rafael; Balafas, Evangelos; Kadoglou, Nikolaos P.E.; Tseti, Ioulia; Skaltsa, Helen; Kostomitsopoulos, Nikolaos; Iliodromitis, E K; Valsami, Georgia; Andreadou, Ioanna

doi:10.1016/j.numecd.2017.08.005

Cited by 30 publications

(17 citation statements)

References 35 publications

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“…The results of the present work, in conjunction to the previously published showing the cardioprotective and anti‐atherosclerotic effect of SFE, consist great evidence of the pharmacological properties of SFE and can be used to support the study and exploration of its potential therapeutic applications.…”

Section: Resultssupporting

confidence: 77%

“…However, a wide‐spectrum of potential pharmaceutical applications has been reported for saffron with the most remarkable effects being attributed to its main natural carotenoids, crocin and crocetin . In parallel, an increasing number of research studies on the possible clinical uses of saffron have been conducted, mainly against malignancies and Alzheimer's disease, as well as regarding its anti‐atherosclerotic and cardioprotective effect . Experiments conducted in rodents, showed that orally administered crocins are hydrolyzed to crocetin before being incorporated into blood circulation and that crocetin is likely to be metabolized to glucuronide conjugates both in the intestinal mucosa and in the liver of mice …”

Section: Introductionmentioning

confidence: 99%

“…Most of the relevant PK studies are conducted after administration of the main active constituents namely crocin or its main metabolite crocetin, while there is only one study where serum crocetin levels are measured with a developed HPLC method in the plasma of four healthy volunteers after consumption of one cup of saffron tea . We recently performed preliminary pharmacokinetic experiments for the selection of the proper dose range to study the anti‐atherosclerotic and cardioprotective effects of saffron . However, a systematic study and evaluation of basic serum and tissue pharmacokinetic parameters after administration of saffron extract are missing and could help to explore its possible pharmaceutical applications.…”

Section: Introductionmentioning

confidence: 99%

“…[1,2] In parallel, an increasing number of research studies on the possible clinical uses of saffron have been conducted, mainly against malignancies [6][7][8][9] and Alzheimer's disease, [6,9,10] as well as regarding its anti-atherosclerotic and cardioprotective effect. [11,12] Experiments conducted in rodents, showed that orally administered crocins are hydrolyzed to crocetin before being incorporated into blood circulation and that crocetin is likely to be metabolized to glucuronide conjugates both in the intestinal mucosa and in the liver of mice. [13,14] To explain the chemical and pharmacological properties of saffron, the chemical profile of the extract deriving from the stigmatic lobes of the C. sativus L. flower should be evaluated.…”

Section: Introductionmentioning

confidence: 99%

“…[23] We recently performed preliminary pharmacokinetic experiments for the selection of the proper dose range to study the anti-atherosclerotic and cardioprotective effects of saffron. [11,12] However, a systematic study and evaluation of basic serum and tissue pharmacokinetic parameters after administration of saffron extract are missing and could help to explore its possible pharmaceutical applications.…”

Section: Introductionmentioning

confidence: 99%

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Preparation, chemical characterization and determination of crocetin's pharmacokinetics after oral and intravenous administration of saffron (Crocus sativus L.) aqueous extract to C57/BL6J mice

Christodoulou

Grafakou

Skaltsa

et al. 2018

Journal of Pharmacy and Pharmacology

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Objectives To prepare a lyophilized saffron aqueous extract (SFE) and determine its chemical profile and serum and tissue pharmacokinetics after intravenous and oral administration to C57/Bl6J mice. Methods Lyophilized SFE was prepared, characterized using semi‐preparative HPLC and NMR analysis, and stability studies at room temperature, and was quantified for crocin content with an HPLC‐PDA method. After intravenous and oral administration of SFE (60 mg/kg, reconstituted with water for injection) to C57/Bl6J mice, crocetin (derived from in vivo crocin hydrolysis) serum and tissue levels (unconjugated and total) were measured with an HPLC‐PDA method and subjected to compartmental and non‐compartmental PK analysis. Key findings Saffron aqueous extract was rich in all‐trans‐crocin (27.8 ± 0.1% w/w) and stable for more than 15 months. One‐compartment PK model described crocetin's (unconjugated) kinetics after intravenous administration of SFE, while a first‐order kinetic parameter described the rate of crocetin biotransformation to crocetin metabolite (conjugated). Α οne‐compartment PK model with first‐order absorption described crocetin and crocetin's metabolite kinetics after SFE oral administration. Relative oral bioavailability was calculated at 1.17 for total crocetin. Tissue NCA PK analysis revealed extensive crocetin distribution to liver and kidneys. Conclusions SFE is a stable lyophilized extract rich in all‐trans‐crocin. The PK study allowed the estimation of basic PK parameters and the bioavailability of SFE’s main bioactive component, crocetin, after peros administration.

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Section: Resultssupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preparation, chemical characterization and determination of crocetin's pharmacokinetics after oral and intravenous administration of saffron (Crocus sativus L.) aqueous extract to C57/BL6J mice

Christodoulou

Grafakou

Skaltsa

et al. 2018

Journal of Pharmacy and Pharmacology

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A review on herbal Nrf2 activators with preclinical evidence in cardiovascular diseases

Syed

Ram

Murty

et al. 2021

Phytotherapy Research

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Cardiovascular diseases (CVDs) are an ever‐growing problem and are the most common cause of death worldwide. The uncontrolled production of reactive oxygen species (ROS) and the activation of ROS associated with various cell signaling pathways with oxidative cellular damage are the most common pathological conditions connected with CVDs including endothelial dysfunction, hypercontractility of vascular smooth muscle, cardiac hypertrophy and heart failure. The nuclear factor E2‐related factor 2 (Nrf2) is a basic leucine zipper redox transcription factor, together with its negative regulator, kelch‐like ECH‐associated protein 1 (Keap1), which serves as a key regulator of cellular defense mechanisms to combat oxidative stress and associated diseases. Multiple lines of evidence described here support the cardiac protective property of Nrf2 in various experimental models of cardiac related disease conditions. In this review, we emphasized the molecular mechanisms of Nrf2 and described the detailed outline of current findings on the therapeutic possibilities of the Nrf2 activators specifically from herbal origin in various CVDs. Based on evidence from various preclinical experimental models, we have highlighted the activation of Nrf2 pathway as a budding therapeutic option for the prevention and treatment of CVDs, which needs further investigation and validation in the clinical settings.

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The cardiovascular‐protective properties of saffron and its potential pharmaceutical applications: A critical appraisal of the literature

Kadoglou

Christodoulou

Kostomitsopoulos

et al. 2021

Phytotherapy Research

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Saffron, the dried stigma of Crocus sativus L., is used in traditional medicine for its healing properties and the treatment of various pathological conditions. The present literature review aimed to summarize and evaluate the preclinical and clinical data regarding the protective effects and mechanisms of saffron and its main components (crocin, crocetin, safranal) on cardiovascular risk factors and diseases. Many in vitro and animal studies have been conducted implicating antioxidant, hypolipidemic, antidiabetic, and antiinflammatory impact of saffron and its constituents. Notably, there is evidence of direct atherosclerosis regression and stabilization in valid atherosclerosis-prone animal models. However, current clinical trials have shown mostly weak effects of saffron and its constituents on cardiovascular risk factors: (a) Modest lowering of fasting blood glucose, without significant reduction of HbA1c in type 2 diabetic patients, (b) moderate/controversial hypolipidemic effects, (c) negligible hypotensive effect, and (d) inconsistent modification of metabolic syndrome parameters. There are important drawbacks in clinical trial design, including the absence of pharmacokinetic/pharmacodynamic tests, the wide variance of doses and cohorts' characteristics, the small number of patients, the short duration.Therefore, large, properly designed, high-quality clinical trials, focusing on specific conditions are required to evaluate the biological/pharmacological activities and firmly establish the clinical efficacy of saffron and its possible therapeutic uses in cardiovascular diseases.

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Saffron ( Crocus sativus ) intake provides nutritional preconditioning against myocardial ischemia–reperfusion injury in Wild Type and ApoE (−/−) mice: Involvement of Nrf2 activation

Cited by 30 publications

References 35 publications

Preparation, chemical characterization and determination of crocetin's pharmacokinetics after oral and intravenous administration of saffron (Crocus sativus L.) aqueous extract to C57/BL6J mice

Preparation, chemical characterization and determination of crocetin's pharmacokinetics after oral and intravenous administration of saffron (Crocus sativus L.) aqueous extract to C57/BL6J mice

A review on herbal Nrf2 activators with preclinical evidence in cardiovascular diseases

The cardiovascular‐protective properties of saffron and its potential pharmaceutical applications: A critical appraisal of the literature

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