Efficacy and Safety of Crocus sativus L. in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial

Tsolaki, Magda; Karathanasi, Elina; Lazarou, Ioulietta; Dovas, Kostas; Verykouki, Eleni; Karacostas, Anastasios; Georgiadis, Kostas; Tsolaki, Anthoula; Adam, Kenneth R.; Kompatsiaris, Ioannis; Sinakos, Z

doi:10.3233/jad-160304

Cited by 65 publications

(77 citation statements)

References 22 publications

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“…13–15 Besides, Crocus sativus tested in AD patients showed to mildly enhance the patinets’ cognitive function. 16,17 Crocus sativus contains more than 150 volatile and aroma-yielding compounds along with carotenoids including zeaxanthin, lycopene, and various α - and β -carotenes. 18 However, Crocus sativus ’s golden yellow-orange color is primarily the result of crocins, which are considered as major constituents; whereas the picrocrocin and safranal are responsible for its bitterness and aroma, respectively.…”

Section: Introductionmentioning

confidence: 99%

Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid β Load and Related Toxicity in 5XFAD Mice

Batarseh

Bharate

Kumar

et al. 2017

ACS Chem. Neurosci.

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Crocus sativus , commonly known as saffron or Kesar, is used in Ayurveda and other folk medicines for various purposes as an aphrodisiac, antispasmodic, and expectorant. Previous evidence suggested that Crocus sativus is linked to improving cognitive function in Alzheimer’s disease (AD) patients. The aim of this study was to in vitro and in vivo investigate the mechanism(s) by which Crocus sativus exerts its positive effect against AD. The effect of Crocus sativus extract on Aβ load and related toxicity was evaluated. In vitro results showed that Crocus sativus extract increases the tightness of a cell-based blood-brain barrier (BBB) model and enhances transport of Aβ. Further in vivo studies confirmed the effect of Crocus sativus extract (50 mg/kg/day, added to mice diet) on the BBB tightness and function that was associated with reduced Aβ load and related pathological changes in 5XFAD mice used as an AD model. Reduced Aβ load could be explained, at least in part, by Crocus sativus extract effect to enhance Aβ clearance pathways including BBB clearance, enzymatic degradation and ApoE clearance pathway. Furthermore, Crocus sativus extract upregulated synaptic proteins and reduced neuroinflammation associated with Aβ pathology in the brains of 5XFAD mice. Crocin, a major active constituent of Crocus sativus and known for its antioxidant and antiinflammatory effect, was also tested separately in vivo in 5XFAD mice. Crocin (10 mg/kg/day) was able to reduce Aβ load but to a lesser extent when compared to Crocus sativus extract. Collectively, findings from this study support the positive effect of Crocus sativus against AD by reducing Aβ pathological manifestations.

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Section: Introductionmentioning

confidence: 99%

Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid β Load and Related Toxicity in 5XFAD Mice

Batarseh

Bharate

Kumar

et al. 2017

ACS Chem. Neurosci.

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“…placebo [20]; 12 weeks of 7.5 g/day Choto-san extract [TJ-47] versus no treatment [30]; 52 weeks of Crocus extract versus waitlist [29]). Two other studies [27, 28] reported similar changes in the control condition: both reported increased P300 amplitudes (26 weeks of 5 mg/day donepezil [27, 28] or 1.5 mg/day rivastigmine [28]), and 1 reported reduced P300 latencies (26 weeks of 5 mg/day donepezil) [27].…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Intervention Studies Examining Nutritional and Herbal Therapies for Mild Cognitive Impairment and Dementia Using Neuroimaging Methods: Study Characteristics and Intervention Efficacy

Steiner

Mathersul

MacMillan

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Neuroimaging facilitates the assessment of complementary medicines (CMs) by providing a noninvasive insight into their mechanisms of action in the human brain. This is important for identifying the potential treatment options for target disease cohorts with complex pathophysiologies. The aim of this systematic review was to evaluate study characteristics, intervention efficacy, and the structural and functional neuroimaging methods used in research assessing nutritional and herbal medicines for mild cognitive impairment (MCI) and dementia. Six databases were searched for articles reporting on CMs, dementia, and neuroimaging methods. Data were extracted from 21/2,742 eligible full text articles and risk of bias was assessed. Nine studies examined people with Alzheimer's disease, 7 MCI, 4 vascular dementia, and 1 all-cause dementia. Ten studies tested herbal medicines, 8 vitamins and supplements, and 3 nootropics. Ten studies used electroencephalography (EEG), 5 structural magnetic resonance imaging (MRI), 2 functional MRI (fMRI), 3 cerebral blood flow (CBF), 1 single photon emission tomography (SPECT), and 1 positron emission tomography (PET). Four studies had a low risk of bias, with the majority consistently demonstrating inadequate reporting on randomisation, allocation concealment, blinding, and power calculations. A narrative synthesis approach was assumed due to heterogeneity in study methods, interventions, target cohorts, and quality. Eleven key recommendations are suggested to advance future work in this area.

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“…Incidence of side effects was comparable in the two treatment groups, while vomiting was associated with the donepezil treatment. Furthermore, a randomized single‐blind 12‐month study showed that saffron improved the cognitive decline in 17 participants with amnesia (Tsolaki et al, ). Moreover, saffron proved comparable to memantine in reducing cognitive decline in patients with moderate to severe Alzheimer's disease (Farokhnia et al, ).…”

Section: Potential Therapeutic Applications Of Saffronmentioning

confidence: 99%

“…Despite being multiple mechanistic studies, only a few clinical trials proved that saffron could improve depression symptoms and stimulate cognitive functions in patients suffering from Alzheimer's disease (Broadhead, Chang, Grigg, & McCluskey, ; Farokhnia et al, ; Tsolaki et al, ). Due to its supposed aphrodisiac effects, saffron has also been tested in preclinical and clinical studies regarding male and female sexual disorders, mainly caused by major depression (Hosseinzadeh, Ziaee, & Sadeghi, ).…”

Section: Introductionmentioning

confidence: 99%

Phytotherapic use of the Crocus sativus L. (Saffron) and its potential applications: A brief overview

Leone

Recinella

Chiavaroli

et al. 2018

Phytotherapy Research

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Crocus sativus L. (Saffron) has long been known for multiple target therapeutic uses. The plant metabolism is well investigated and the main metabolites related to saffron organoleptic qualities are crocin, crocetin, picrocrocin, and safranal. Particularly, the most abundant of them, such as crocin and safranal, are investigated for their multiple biological activities and known as potential drugs. We aimed to review the constituent features of the plant, along with its potential therapeutic effects in depression, neurodegenerative diseases, diabetes mellitus, atherosclerosis, cancer, and sexual dysfunction. A systematic literature search was conducted in PubMed, Medline, Scopus, and EMBASE, with particular attention to preclinical and clinical studies. Although saffron and its components showed potential clinical applications, further investigations are necessary to confirm the effective use of "Red Gold" and its real applications in clinical practice.

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Efficacy and Safety of Crocus sativus L. in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial

Cited by 65 publications

References 22 publications

Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid β Load and Related Toxicity in 5XFAD Mice

Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid β Load and Related Toxicity in 5XFAD Mice

A Systematic Review of Intervention Studies Examining Nutritional and Herbal Therapies for Mild Cognitive Impairment and Dementia Using Neuroimaging Methods: Study Characteristics and Intervention Efficacy

Phytotherapic use of the Crocus sativus L. (Saffron) and its potential applications: A brief overview

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