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Crocus sativus L. in the treatment of mild to moderate depression: A double-blind, randomised and placebo controlled trial
Abstract
Depression is a serious disorder in today's society. With estimates of lifetime prevalence as high as 21% of the general population in some developed countries. As a therapeutically plant, saffron it is considered an excellent stomach ailment and an antispasmodic, helps digestion and increases appetite. It is also used for depression in Persian traditional medicine. Our objective was to assess the efficacy of stigmas of Crocus sativus (saffron) in the treatment of mild to moderate depression in a 6-week double-blind, placebo controlled and randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind, placebo controlled, single-center trial and randomized trial, patients were randomly assigned to receive capsule of saffron 30 mg/day (BD) (Group 1) and capsule of placebo (BD) (Group 2) for a 6-week study. At 6 weeks, Crocus sativus produced a significantly better outcome on Hamilton Depression Rating scale than placebo (d.f.=1, F= 18.89, p<0.001). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large- scale trial is justified.
... Among these medications, antidepressants are used and have been reported to be effective in improving ADHD symptoms (Banaschewski et al. 2004;Zarinara et al. 2010;Salardini et al. 2016). Furthermore, these agents also produce several adverse reactions, such as anticholinergic effects, orthostatic hypotension, and arrhythmias (Demyttenaere 1997;Akhondzadeh et al. 2005). So far, the outcome with these approved medications for ADHD are often unsatisfactory and there is an empty place to be filled by alternative medications, in particular herbal medicines (Modabbernia and Akhondzadeh 2013). ...
... Similarly, saffron constituents have also been shown to exert ''potential'' antidepressant activities in several clinical trials and experimental models. In addition, saffron was more effective than placebo therapy and could be compared with conventional antidepressants like fluoxetine and imipramine (Akhondzadeh et al. 2004(Akhondzadeh et al. , 2005Akhondzadeh Basti et al. 2007). Thus, we hypothesized that saffron intake would be of benefit in ADHD patients to alleviate symptoms. ...
... Although this study has several advantages, such as a double-blind randomized design and the strict adjustment for baseline clinical variables, there are some limitations. The lack of a placebocontrolled trial is the main limitation; however, the efficacy of saffron in relation to placebo for treatment of depression has been documented (Akhondzadeh et al. 2005). The study population size was small and the short follow-up period should also be considered. ...
Objective:
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders of childhood and adolescence. About 30% of patients do not respond to stimulants or cannot tolerate their side effects. Thus, alternative medication, like herbal medicine, should be considered. The aim of this trial is to compare the safety and efficacy of Crocus sativus (saffron) versus methylphenidate in improving symptoms of children with ADHD.
Methods:
In a 6-week randomized double-blind study, 54 patients (children 6-17 years old) with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of ADHD were randomly assigned to receive either 20-30 mg/d (20 mg/d for <30 kg and 30 mg/d for >30 kg) methylphenidate (MPH) or 20-30 mg/d saffron capsules depending on weight (20 mg/d for <30 kg and 30 mg/d for >30 kg). Symptoms were assessed using the Teacher and Parent Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) at baseline and weeks 3 and 6.
Results:
Fifty patients completed the trial. General linear model repeated measures showed no significant difference between the two groups on Parent and Teacher Rating Scale scores (F = 0.749, df = 1.317, p = 0.425, and F = 0.249, df = 1.410, p = 0.701, respectively). Changes in Teacher and Parent ADHD Rating Scale scores from baseline to the study end were not significantly different between the saffron group and the MPH group (p = 0.731 and p = 0.883, respectively). The frequency of adverse effects was similar between saffron and MPH groups.
Conclusion:
Short-term therapy with saffron capsule showed the same efficacy compared with methylphenidate. Nevertheless, larger controlled studies with longer treatment periods are necessary for future studies.
... In one study [20], the patients involved were not suffering from mild to moderate depression, therefore, this study did not comply with our PICO. After reviewing the articles, it became clear that one trial, including three treatment arms, was published in two different papers [21,22]. Consequently, we considered these two papers as one RCT. ...
... Consequently, we considered these two papers as one RCT. Therefore, a total of 11 placebocontrolled, randomized trials with 531 patients were included in the qualitative analysis [21][22][23][24][25][26][27][28][29][30][31][32]. ...
... Altogether, ten articles reporting on nine trials were included in our final quantitative analysis [21][22][23][24][25][26][27][29][30][31]. Akhondzadeh et al. [32] provided the baseline HAM-D scores numerically, but the outcomes were shown only graphically in a figure, therefore, we could not include the results of this trial in the quantitative analysis. ...
Herbal products, especially Hypericum perforatum extracts, have been widely used as first-line treatments for mild to moderate depression. Recently, several randomized, controlled clinical trials have been conducted to evaluate the efficacy of another plant, saffron (Crocus sativus), in mild to moderate depression. We have carried out a literature review of currently available published randomized, controlled clinical trials to give an up-to-date evaluation of the efficacy of saffron in mild to moderate depression, compared to placebo or routinely used antidepressants. The meta-analysis is reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using the PICO (patients, intervention, comparison, outcome) format and was conducted using the statistical programs Comprehensive Meta-analysis and RevMan. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for relevant studies. Only placebo or active controlled, randomized clinical studies involving patients suffering from mild to moderate depression and using pharmacological doses of saffron per os were included. Hedgesʼ g was used to calculate effect sizes. Risk of bias was assessed using the Cochrane Collaboration tool, and heterogeneity was tested by both performing the Cochranʼs Q test and calculating Higginsʼ I2 indicator. Eleven randomized trials were included in the qualitative analysis, and nine were pooled for statistical analysis. According to the present meta-analysis, saffron has a significant effect on the severity of depression. Available data from randomized, controlled clinical trials support that saffron is significantly more effective than placebo (g = 0.891; 95% CI: 0.369 – 1.412, p = 0.001), and non-inferior to tested antidepressant drugs (g = − 0.246; 95% CI: − 0.495 – 0.004, p = 0.053).
... Previous studies have pointed to the possible applicability of saffron for sexual dysfunction in both men and women (Hosseinzadeh et al., 2008;Kashani et al., 2013;Shamsa et al., 2009). Furthermore, other studies have indicated that saffron can be useful, at least as a supplement, in treating depressive and anxiety disorders (Agha-Hosseini et al., 2008;Akhondzadeh Basti et al., 2007;Akhondzadeh et al., 2004;Akhondzadeh et al., 2005). Saffron has been seen to possess antinociceptive effects, which might reduce pain-related discomfort during a sexual relationship through peripheral blockage of pain detection (Hosseinzadeh and Younesi, 2002). ...
... The dysfunctions caused by depression were more prominent in the pain, lubrication, and arousal domains of FSFI as studied by Mahmoud et al. (Mahmoud et al., 2018). It, thus, can be hypothesized that the established anti-depressive properties of saffron might ameliorate sexual dysfunction (Akhondzadeh Basti et al., 2007;Akhondzadeh et al., 2004;Akhondzadeh et al., 2020;Akhondzadeh et al., 2005;Milajerdi et al., 2018). A similar rationale can also be laid out for the efficacy of saffron as an anxiolytic agent and its relation to improving sexual dysfunction (Lo and Kok, 2018). ...
Objective:
One of the traditional aphrodisiacs used in various cultures is Crocus sativus, commonly called saffron. Previous studies have pointed to the possible applicability of saffron for sexual dysfunction in both men and women. This study investigates the effects of saffron capsules on female sexual dysfunction.
Materials and methods:
This study was a parallel-group, double-blind, randomized, placebo-controlled clinical trial. Participants, who were married women between 18 and 55 years of age suffering from severe sexual dysfunction, were randomized to receive either 15 mg Crocus sativus capsules twice daily or placebo. The treatment continued for 6 weeks, and patients were evaluated every 2 weeks. The primary outcome was the change in the female sexual function index score. Other outcomes included the female sexual function index sub-domains.
Results:
Seventy -four patients were equally randomized to each group, and 34 in each group completed the trial. Participants in both groups experienced improved total scores at each visit. However, a repeated-measures ANOVA revealed that time treatment differed between groups in favor of the saffron group (p=0.050). During the 6th week follow-up, the saffron group had a 62% score improvement from baseline. Desire, lubrication, and satisfaction were female sexual function index domains in which saffron demonstrated superiority over placebo. The adverse event profile was similar for the groups, and no participant discontinued treatment.
Conclusion:
Findings of this study suggest that saffron might be a safe and effective option to ameliorate female sexual dysfunction. Further robust research is warranted.
... It has traditionally been used as an analgesic and sedative, and as a treatment for gastrointestinal, respiratory and infectious diseases (Hosseinzadeh and Nassiri-Asl, 2013). As an antidepressant agent, saffron has been shown through several randomised- controlled trials to be more effective than placebo ( Akhondzadeh et al., 2005;Moshiri et al., 2006) and of equivalent efficacy as the antidepressants fluoxetine (Akhondzadeh Basti et al., 2007;Noorbala et al., 2005;Shahmansouri et al., 2014), imipramine (Akhondzadeh et al., 2004), and citalopram ( Ghajar et al., 2017) for the treatment of mild-to-moderate depression. Moreover, the antidepressant efficacy of saffron has been confirmed in two meta-analyses and systematic reviews ( Hausenblas et al., 2013;Lopresti and Drummond, 2014). ...
... The results of this study provide first evidence supporting the beneficial effects of a standardised saffron extract (affron ® ) for the treatment of anxiety and depressive symptoms in teenage youth. In several randomised-controlled studies, saffron has been shown to be an effective antidepressant and anxiolytic agent in adults with mild-to-moderate depression, with several studies confirming greater efficacy than placebo ( Akhondzadeh et al., 2005;Moshiri et al., 2006) and an equivalent efficacy to the antidepressants fluoxetine (Akhondzadeh Basti et al., 2007;Noorbala et al., 2005;Shahmansouri et al., 2014), imipramine (Akhondzadeh et al., 2004), and citalopram ( Ghajar et al., 2017); however, prior to this study, there was no research examining its efficacy in youth ( Hausenblas et al., 2013;Lopresti and Drummond, 2014). In this 8- week, randomised, double-blind, placebo-controlled study, saffron was effective in reducing overall internalising symptoms and exhibited greatest benefits on symptoms associated with separation anxiety, depression, and social phobia. ...
Background:
Saffron has antidepressant and anxiolytic effects in adults with mild-to-moderate depression. However, this is the first study examining its mood-related effects in teenagers.
Methods:
In this 8-week, randomised, double-blind, placebo-controlled study, youth aged 12-16 years, with mild-to-moderate anxiety or depressive symptoms were given tablets containing placebo or a saffron extract (affron®, 14 mg b.i.d). The youth and parent versions of the Revised Child Anxiety and Depression Scale (RCADS) were used as outcome measures.
Results:
80 participants were enrolled and 68 completed the study. Based on youth self-reports, affron®was associated with greater improvements in overall internalising symptoms (p = 0.049), separation anxiety (p = 0.003), social phobia (p = 0.023), and depression (p = 0.016). Total internalising scores decreased by an average of 33% compared to 17% in the placebo group (p = 0.029). However, parental reports of improvements were inconsistent as mean improvements in RCADS scores were greater in the saffron group (40% vs 26%) (p = 0.026), although no other significant differences were identified. affron®was well-tolerated and there was a trend of reduced headaches in participants on the active treatment.
Limitations:
The use of a self-report instrument, limited study duration, single treatment dose, and non-clinical sample used in this study limit the generalisability of study findings.
Conclusion:
The administration of a standardised saffron extract (affron®) for 8 weeks improved anxiety and depressive symptoms in youth with mild-to-moderate symptoms, at least from the perspective of the adolescent. However, these beneficial effects were inconsistently corroborated by parents.
... Placebo 6-week C. sativus produced a significantly better outcome on Hamilton depression rating Scale than placebo. Akhondzadeh et al., 2005 40 patients Saffron (60 mg/day) ...
... At the end of this randomized controlled trial, petal of C. sativus produced a significantly better outcome on Hamilton Depression Rating Scale than placebo and there were no differences in the case of side effects ( Moshiri et al., 2006). In a similar study by Akhondzadeh et al., the same results were obtained ( Akhondzadeh et al., 2005). Sahraian and colleagues also designed a double blind placebo controlled clinical trial where 40 patients suffering from major depression according to DSM-IV criteria were randomly allocated to take either fluoxetine and saffron (20 patients) or fluoxetine and placebo (20 patients). ...
Background:
Depression and anxiety are two common mental health problems with high economic and social costs. Currently, a number of treatments are available for patients with depression and anxiety disorders such as psychotherapy, electroconvulsive therapy and antidepressant drugs. Due to safety concerns, adverse effects, limited efficacy and low tolerability associated with many antidepressant and anti-anxiety medications, identification of novel agents with less toxicity and more favorable outcome is warranted.
Methods:
The current article provides a non-systematic review of the available in vitro, in vivo and clinical evidence on the efficacy, safety and mechanisms of action of saffron and its active ingredients in the treatment of anxiety, depression and other mental disorders.
Results:
Several interesting data have been reported about the antidepressant and anti-anxiety properties of saffron, the dried stigmas of Crocus sativus L., in several preclinical and clinical studies. In particular, a number of clinical trials demonstrated that saffron and its active constituents possess antidepressant properties similar to those of current antidepressant medications such as fluoxetine, imipramine and citalopram, but with fewer reported side effects.
Conclusion:
Saffron may exert antidepressant effects and represents an efficacious and safe treatment.
... Saffron is used in natural medicine as anti-catarrhal, anti-spasmodic, nerve sedative, gingival seda-tive, diaphoretic, carminative and expectorant [15]. In a relatively recent pharmacological studies, saffron demonstrated numerous health properties such as anti-cancer and anti-toxic [16,[30][31][32][33], antioxidant [14,18,21,[34][35][36], antinociceptive and anti-inflammatory [37,38], anti-atherosclerosis [20,22,39], anti-diabetic and insulin resistance [40][41][42], hypotensive [43], hypolipidemic [44] and hypoglycemic [45][46][47], antidepressant and mood improving [48][49][50][51][52][53] effects. Although numerous studies have been reported in different medicinal properties of saffron and its constituents but in this paper we concentrated on scientific evidence demonstrating the potential of saffron against obesity and related metabolic disorders. ...
... Crocin also reduced immobility time and increased climbing time at dose 50-600 mg/kg may be via individual uptake inhibition of dopamine and norepinephrine [48]. In another study, it was found that saffron supplementation statistically improved the moods of people compared with the placebo group after receiving 30 mg/day of saffron for six weeks evaluated based on the Hamilton Depression Rating Scale (HAM-D) [49]. A similar study by Noorbala and colleagues determined that saffron extracts were effective in treating mild to moderate depression similar to fluoxetine (the antidepressant, Prozac) after 30 mg/day intake for six weeks [51]. ...
Obesity is associated with various diseases, particularly diabetes, hypertension, osteoarthritis and heart disease. Research on possibilities of herbal extracts and isolated compounds from natural products for treating obesity has an upward trend. Saffron (Crocus Sativus L. Iridaceae) is a source of plant polyphenols/carotenoids, used as important spice and food colorant in different parts of the world. It has also been used in traditional medicine for treatment of different types of illnesses since ancient times. Many of these medicinal properties of saffron can be attributed to a number of its compounds such as crocetin, crocins and other substances having strong antioxidant and radical scavenger properties against a variety of radical oxygen species and pro-inflammatory cytokines. The aim of this article is to assess the potential role of saffron and its constituents in the regulation of metabolic functions, which can beneficially alter obesity pathophysiology.
... Crocus sativus is used in Asian and, in particular, Indian (Ayurveda) and Persian (Islamic) traditional medicine (ITM) as a sedative agent to strengthen the body against such stresses as trauma and anxiety, an anticonvulsant and memory enhancer, and a remedy for alleviation of chronic fatigue, depression, and inflammation [71,135]. This therapeutic activity of Crocus, known since the 6th century BC, has been confirmed in the most recent basic research conducted on animals (rodents) and in human clinical studies [134,[175][176][177][178][179][180][181][182][183]. ...
Psychotropic effect of Crocus sativus L. (family Iridaceae) biologically active chemical compounds are quite well documented and they can therefore be used in addition to the conventional pharmacological treatment of depression. This systematic review on antidepressant compounds in saffron crocus and their mechanisms of action and side effects is based on publications released between 1995–2022 and data indexed in 15 databases under the following search terms: antidepressant effect, central nervous system, Crocus sativus, cognitive impairement, crocin, crocetin, depression, dopamine, dopaminergic and serotonergic systems, picrocrocin, phytotherapy, neurotransmitters, safranal, saffron, serotonin, and biologically active compounds. The comparative analysis of the publications was based on 414 original research papers. The investigated literature indicates the effectiveness and safety of aqueous and alcoholic extracts and biologically active chemical compounds (alkaloids, anthocyanins, carotenoids, flavonoid, phenolic, saponins, and terpenoids) isolated from various organs (corms, leaves, flower petal, and stigmas) in adjuvant treatment of depression and anxiety. Monoamine reuptake inhibition, N-methyl-d-aspartate (NMDA) receptor antagonism, and gamma-aminobutyric acid (GABA)-α agonism are the main proposed mechanism of the antidepressant action. The antidepressant and neuroprotective effect of extract components is associated with their anti-inflammatory and antioxidant activity. The mechanism of their action, interactions with conventional drugs and other herbal preparations and the safety of use are not fully understood; therefore, further detailed research in this field is necessary. The presented results regarding the application of C. sativus in phytotherapy are promising in terms of the use of herbal preparations to support the treatment of depression. This is particularly important given the steady increase in the incidence of this disease worldwide and social effects.
... It has been demonstrated in clinical double blind trials that saffron is efficacious in the treatment of depression. In one of the studies, clear effects of saffron extracts were shown when compared with placebo [3]. In other trials the effect was compared with that of fluoxetine ("Prozac") [4] and imipramine [2], conventional standard treatments for depression. ...
Since antiquity, saffron (Crocus sativus) has been the most rare and most expensive spice. Adulterations have always been a major obstacle for supplies with pure herbal material. With time passing by, the methods of adulteration have evolved. Those currently used reveal a good knowledge of organic chemistry. According to recent observations and studies, a large part of saffron newly arriving on the international markets gets there by indirect pathways without any traceability, which is also the cause for numerous deliberate adulterations. In the improvement of saffron quality and the development of specific extracts we followed the rules of the European commission directive 178/2002/EC and the WHO guideline Good Agricultural and Collection Practice (GACP) regarding traceability. Within a complex program aimed on the guarantee of reproducibility and diverse qualitative aspects the traceability of our raw material is ensured by following strictly defined protocols. Thus, we obtain a 100% pure supply of saffron from cultivars specifically selected for their effect or phytochemical composition.
... Akhondzadeh et.al.(2005) conducted a study showing the efficacy of Crocus sativus(saffron) in the treatment of mild to moderate depression [43] . Smelling cinnamon can improve brain function and our mood. ...
Food and mood are regular consistent part of our lives and they inevitably get tangled up together. This review study aims to find out the physiochemical and biochemical relationships and the exact mechanism that binds food with mood. Results showed that caffeine improves vigilance, alertness, mood and cognitive processes during and after exercise. L-theanine a major component of tea, has anxiolytic and calming effect due to its up-regulation of inhibitory neurotransmitters and possible modulation of serotonin and dopamine in selected areas. Antidepressant-like effect of chocolate can most likely be attributed to the antioxidant potential of cocoa polyphenol which reduces hunger and elevates mood.n-3 PUFA present in fish oil exerts anti-depressant effect. Folic acid and Vitamin C is beneficial for the reduction of Childhood Depression.
... In a randomized, double-blind study, 30 mg of saffron extract (in capsules) given for 6 weeks resulted in significant alleviation of depression compared to placebo group, and no side effects were recorded. Many follow-ups double blind trials carried out on saffron preparation compared with imipramine and fluoxetine; showed that saffron possessed antidepressant effects [59,[45][46][47]. ...
Medicinal plants can exert antidepressant activity by many mechanisms included neutralization of various stress mediators (regulate the activity of the hypothalamic-pituitary-adrenal axis and reduce CRF, and ACTH and corticosterone) [5], interaction with serotonergic systems (5-HT3, 5HT2A, 5-HT1A), noradrenergic (α1 and α2 receptors) and dopaminergic (D1 and D2) receptors [6],restoring monoamine transmitters and their receptors to normal limits in certain regions of the cortex, in addition to reducing of oxidative stress and amelioration of inflammatory mediators. The current review discussed the antidepressant activity of medicinal plants, with emphasis on their mechanisms of action.
... Depression is 1 of the diseases for which researchers and psychiatrists have adopted various medical and nonpharmacologic methods for treatment. The use of group counseling, meaning therapy 12 ; music therapy 13 ; the use of Quranic sound 14 ; and the use of herbal medicines such as licorice, 15 lemon balm, 16 and saffron 17 as nonmedicinal methods are studied by researchers. The role of regular consumption of green tea has also been investigated in some studies in which the positive effects on reducing depression have been confirmed. ...
The world’s older population continues to grow at an unprecedented rate. Iran is 1 of the countries where the aging population is higher than the global average. Depression is 1 of the most common issues in older adults that can be managed by nonpharmacologic interventions such as the consumption of green tea. The aim of this study was to determine the effect of green tea consumption on depression in the elderly people. In this quasi-experimental study, 76 elderly people who were residents in a nursing home and met the inclusion criteria were selected through simple random sampling. Then, green tea in 3-g tea bags was brewed in 80°C water and half an hour after breakfast and lunch was given to the participants in a 5-week protocol. One day after the last time of brewing green tea, participants were assessed with a standard depression questionnaire. The obtained data were analyzed using SPSS Version 19 software (IBM Corp, Armonk, NY). The descriptive statistics and Wilcoxon statistical test analysis were also conducted at a significant level of P < .05. Based on the findings, the mean score of the participants’ depression level decreased by 2.5 points after the intervention, which is statistically significant at a 99.9% confidence interval (P = .001). The findings also suggest that the severe depression decreased from 23.6% to 11.1%, moderate depression decreased from 45.8% to 26.4%, and mild depression increased from 30.6% to 45.8%; only severe and moderate depression cases were reduced (P = . 001). The findings of the present study reveal that regular consumption of green tea can lead to a considerable reduction of depression in the elderly people. Accordingly, the consumption of this tea in the elderly people’s diet is recommended, especially those who are resident in the care centers.
... Saffron is not only a widely applied food seasoning; but also it has numerous pharmacological effects. Oral consumption of saffron in small amounts (a daily dose of 100 mg of saffron or 30 mg of saffron hydroalcoholic extract) may induce significant pharmacological effects [109][110][111][112][113][114]. One of the main ingredients of saffron is crocin, which accounts for the yellow pigmentation of the stigmas. ...
Chronic stress and high levels of glucocorticoids produce functional and structural changes in brain and especially in the hippocampus, an important limbic system structure that plays a key role in cognitive functions including learning and memory. Alzheimer's disease (AD) is a chronic neurodegenerative disease that usually starts slowly and worsens over time. Indeed, cognitive dysfunction, neuronal atrophy, and synaptic loss are associated with both AD and chronic stress. Recent preclinical and clinical studies have highlighted a possible link between chronic stress, cognitive decline and the development of AD. It is suggested that Tau protein is an essential mediator of the neurodegenerative effects of stress and glucocorticoids towards the development of AD pathology. Recent findings from animal and humans studies demonstrated that saffron and its main constitutive crocin are effective against chronic stress-induced cognitive dysfunction and oxidative stress and slowed cognitive decline in AD. The inhibitory actions on acetylcholinesterase activity, aggregation of beta-amyloid protein into amyloid plaques and tau protein into neurofibrillary tangles, and also the antioxidant, anti-inflammatory, and the promotion of synaptic plasticity effects are among the possible mechanisms to explain the neuroprotective effects of saffron. New evidences demonstrate that saffron and its main component crocin might be a promising target for cognition improvement in AD and stress-related disorders.
... Therefore, natural compounds could be potentially useful in the treatment of AD depression [35]. Saffron has anti-depressive properties and has been shown to be superior to placebo and equal to an SSRI and a TCA in Table 4 Cognitive and functional status outcomes various RCTs [40][41][42]. However, SSRIs may cause serotonin syndrome, agitation, insomnia, sexual dysfunction, dizziness, and other symptoms, while TCAs are responsible for anticholinergic effects (therefore, they are generally avoided in AD) and cardiac arrhythmias [35]. ...
IntroductionImprovement of cognitive function may be desirable for healthy individuals and clinically beneficial for those with cognitive impairment such as from Alzheimer’s disease (AD) or mild cognitive impairment (MCI). The aim of this systematic review is to investigate the cognitive effects of oral saffron intake, in patients with MCI/AD and/or in non-demented individuals, by following the PRISMA guidelines.Methods
We performed a literature search on MedLine, Cochrane library, and ClinicalTrials.gov to identify randomized controlled trials (RCTs) investigating the effects of oral saffron administration in patients with MCI/AD and/or in non-demented individuals.ResultsFive studies (enrolling 325 individuals) met our inclusion criteria. Four studies included patients with MCI/AD, and one study included cognitively normal individuals. Saffron was well-tolerated in all groups. Regarding cognitively impaired patients, scores on Alzheimer’s Disease Assessment Scale-cognitive subscale or Mini mental state examination were significantly better when saffron was compared with placebo and did not differ significantly when saffron was compared with donepezil or memantine. Saffron effects on functional status were similar with its effects on cognition.Conclusions
Saffron was shown to be equally effective to common symptomatic drugs for MCI/AD and resulted in no difference in the incidence of side effects, when compared with placebo or drugs. The promising results should be seen cautiously, since the evidence was derived from studies with potentially high risk of bias (ROB). RCTs with larger sample sizes and low ROB are required to definitively assess the potential role of saffron as an MCI/AD treatment.
... A significant number of people are seeking alternative medicine for the treatment of various diseases. Hence, the use of complementary and alternative medicine is constantly increasing [9]. As an alternative treatment, herbal medicines may have a relative superiority and ...
Hysterosalpingography is one of the essential diagnostic methods for examining women who have difficulty becoming pregnant. This procedure is somehow invasive and is associated with numerous complications such as allergic sensitivity, pain, abdominal cramps and shock. Therefore, this study aimed to investigate the effect of evening primrose on cervical length and pain during and after hysterosalpingography. In this double-blind clinical trial, 66 candidates for hysterosalpingography were randomly divided into two groups. A group received 1000 mg of evening primrose orally for two days prior to hysterosalpingography, while the control group received a placebo drug similar in size to evening primrose three days prior to hysterosalpingography. The pain level was recorded based on the Visual Analogue Scale (VAS), during tenaculum placement but also immediately and four hours after hysterosalpingography. Finally, the data were analyzed using SPSS (version 20). There was a significant difference between the two groups in terms of pain during insertion of speculum and injection of the contrast medium (p <0.05). Less pain was reported in the evening primrose group compared to placebo. There was no significant difference between the two groups in terms of the length and diameter of the cervix (p <0.05). Given the fact that it is a medicinal plant with no complications and can reduce pain during speculum insertion and during contrast medium injection, evening primrose seems to be a good drug for managing pain during hysterosalpingography.
... In addition to the application as a popular food additive, saffron is used in traditional medicine for laxative, and also as an appetizer, a sedative, a muscle relaxant, and a therapeutic agent in hepatic disorders, asthma, bronchitis, nausea, and cardiovascular disorders. The role of saffron in the elimination of dysentery and infection in urinary tract is proved [5] . ...
Background:
The application of methotrexate (MTX) as a chemotherapy agent and immune system suppressant has various side effects. Crocin, a xanthine derivative plant, has many therapeutic benefits. This study was planned to assess the effect of crocin on renal toxicity of MTX in a rat model.
Methods:
Forty eight rats were divided randomly into eight groups (n = 6), which received normal saline, MTX, crocin, and MTX + crocin for 28 days intraperitoneally. The levels of oxidative stress in kidney and blood serum were measured, and the kidney was analyzed histologically.
Results:
MTX caused an enhancement in the levels of thiobarbituric acid reactive substances and biochemical marker (creatinine and blood urea nitrogen [BUN]). Besides, a significant decrease was observed in tissue parameters and antioxidant capacity compared to the normal control group (p < 0.001). The crocin and crocin + MTX decreased the biochemical markers, the levels of thiobarbituric acid reactive species, and tissue parameters considerably at entire dose (12.5, 25, and 50 mg/kg) and enhanced the antioxidant capacity levels compared to the MTX group (p < 0.001).
Conclusion:
Administration of crocin improves the damage caused by MTX in rats. The crocin by the establishment of balance in the levels of antioxidant prevents the damage to the renal cell membrane, and subsequently the renal damage repairs.
... Akhondzadeh et.al.(2005) conducted a study showing the efficacy of Crocus sativus(saffron) in the treatment of mild to moderate depression [43] . Smelling cinnamon can improve brain function and our mood. ...
Food and mood are regular consistent part of our lives and they inevitably get tangled up together. This review study aims to find out the physiochemical and biochemical relationships and the exact mechanism that binds food with mood. Results showed that caffeine improves vigilance, alertness, mood and cognitive processes during and after exercise. L-theanine a major component of tea, has anxiolytic and calming effect due to its up-regulation of inhibitory neurotransmitters and possible modulation of serotonin and dopamine in selected areas. Antidepressant-like effect of chocolate can most likely be attributed to the antioxidant potential of cocoa polyphenol which reduces hunger and elevates mood.n-3 PUFA present in fish oil exerts anti-depressant effect. Folic acid and Vitamin C is beneficial for the reduction of Childhood Depression.
... Saffron and its metabolites have been shown to be effective in different models of psychiatric disorders, including depression and anxiety, comparing their effects with imipramine or fluoxetine [135][136][137][138][139]. A study showed that there are no significant differences between the use of saffron and the drug [140]. ...
Crocus sativus L. has been cultivated throughout history to obtain its flowers, whose dried stigmas give rise to the spice known as saffron. Crocetin esters, picrocrocin, and safranal are the main metabolites of this spice, which possess a great bioactivity, although the mechanisms of action and its bioavailability are still to be solved. The rest of the flower is composed by style, tepals, and stamens that have other compounds, such as kaempferol and delphinidin, which have an important antioxidant capacity, and these can be applied in foods, phytopharmaceuticals, and cosmetics. The aim of this work was to provide an updated and critical review of the research on the main compounds of Crocus sativus L. flower, including the adequate analytical methods for their identification and quantification, with a focus on their bioactivity and bioavailability.
... In terms of human investigations, three studies ( Akhondzadeh et al., 2005;Mazidi et al., 2016;Moshiri et al., 2006) have demonstrated that saffron extract is more effective than placebo in the treatment of major depression or mixed anxiety and depression (see the discussion in Ghajar et al., 2017;Hausenblas et al., 2015Hausenblas et al., , 2013Moshiri et al., 2015). In a double-blind, randomized study, saffron was found to be more effective than placebo at reducing symptoms of mild-to-moderate postpartum depression (Tabeshpour et al., 2017). ...
Given the moderate efficacy of the currently available antidepressants (ADs) in the treatment of major depressive disorder (MDD), the identification of agents that are both able to enhance the effectiveness of ADs and have a good safety profile is a reasonable task for current psychopharmacology. In addition to the well-known drugs (second-generation antipsychotics, levothyroxine, dopaminergic agents, etc.) for augmentation, investigations suggest that several nutraceuticals and over-the-counter (OTC) drugs may be effective and safe as adjunct therapeutic agents to conventional ADs. To identify such active ingredients we first performed a systematic literature search using PubMed and then conducted both backward and forward citation searches. For the PubMed search, we used the following combinations of keywords: 1) “adjunctive” + “therapy” + “antidepressant”; 2) “add-on” + “therapy” + “antidepressant”; 3) “supplementation” + “therapy” + “antidepressant”. As a result of those efforts, we found more than 20 agents (e.g. S-Adenosyl-L-Methionine; folate; ω-3 fatty acids; curcumin; N-acetylcysteine; saffron; 5-hydroxytryptophan; NSAIDs) that are supposedly effective in the augmentation of standard AD treatment. We discussed the possible mechanisms of the antidepressant actions of those agents, as well as the preclinical and clinical evidence for their efficacy as stand-alone and adjunct treatments for MDD.
... Clinical studies have demonstrated that saffron hydroalcoholic extract at the dose of 20-30 mg/day twice daily, compared to fluoxetine and imipramine, has improved mild and moderate depression (Akhondzadeh et al., 2004;Akhondzadeh et al., 2005;Akhondzadeh et al., 2007;. More recently, reported that 30 mg/day for 4 weeks of crocin significantly improved mood in patients with major depression, but the sample size and short term of the clinical trial limit the scientific value of these results. ...
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.
... Saffron is used traditionally for cooking or perfume, but it appears in several medical indications, as mentioned in recent works focused on in vitro, in vivo and clinical studies. Several potential health benefits of saffron consumption have been described, including mental health, well-being-promoting effects with anti-depressant and anti-anxiety effects, premenstrual syndrome, and men's sexual health and fertility (Agha-Hosseini et al., 2008;Akhondzadeh et al., 2005;Ghadrdoost et al., 2011;Heidary et al., 2008;Mazidi et al., 2016;Papandreou et al., 2011;Shiri et al., 2007). ...
A new UHPLC-DAD-MS method based on a Core-Shell particles column was developed to realize the rapid separation of saffron stigma metabolites (Crocus sativus L.). A single separation of 35 compounds included cis and trans-crocetin esters (crocins), cis-crocetin, trans-crocetin, kaempferol derivatives, safranal, and picrocrocin from pure saffron stigmas. This method permitted the detection of 11 picrocrocin derivatives as the typical group of compounds from saffron as well as the detection of gardenia-specific compounds as typical adulterant markers. The metabolite concentration in a Standardized Saffron Extract (SSE) was determined using the method described herein and by comparison to the ISO3632 conventional method. The safranal content was 5–150 times lower than the value of 2% that was expected via ISO3632 analyses. Using the same Core-Shell separation, geniposide detection appeared to be a relevant approach for detecting the adulteration of saffron by using gardenia.
... Some researchers have suggested that the antidepressant action of safranal is similar to those of fluoxetine and imipramine. [94][95][96] Recently, Agha-Hosseini et al 97 evaluated saffron's action in 50 women with symptoms of premenstrual tension syndrome persisting for more than 6 months. The application of saffron at a dose of 30 mg/day for 2 menstrual cycles caused a significant alleviation in ailments and a symptomatic reduction of mood disturbances according to the Hamilton Depression Rating Scale. ...
Context:
Pathological anxiety, which affects approximately one-third of the world population, is an inadequate, irrational reaction of an organism to the environment and to a potential threat. Despite advancements in pharmacotherapy for anxiety disorders, further studies are still necessary to search for new substances possessing the desired anxiolytic effects, with as few unwanted effects as possible.
Objective:
This study intended to examine the characteristics of medicinal plant materials that exhibit anxiolytic properties, with a special emphasis on the mechanisms of action of their active ingredients on the systems involved in the pathophysiology of anxiety.
Design:
The research team performed a review of the literature, searching well-known online scientific databases, including PubMed, Google Scholar, Medline, ScienceDirect, and SpringerLink. The team searched for the newest research from various regions of the world.
Setting:
The study was done in the Medical University of Silesia (Katowice, Poland).
Results:
The medicinal plant materials presented in the current article undoubtedly influence the central nervous system. Our analysis showed that their mechanism of action is very complicated and appropriately still enigmatic. Among them, V officinalis represents the most thoroughly investigated medicinal plant material that produces anxiolytic, sedative effects. However, extracts of other medicinal plants may also emerge as helpful in the treatment of fear and anxiety and in the prophylaxis of those disorders.
Conclusions:
The current review discusses the most recent data on medicinal plant materials that are effective as anxiolytic treatments, with special emphasis on the neurobiological mechanisms of action of their active ingredients. The research team hopes that the information may open up new directions in the search for drugs capable of enhancing the existing therapy.
... Saffron and its metabolites have proven to be effective in different models of psychiatric disorders, including depression and anxiety. Various studies in clinical environments concluded that the daily administration of 30 mg of saffron could be useful in the management of depression when compared with imipramine or fluoxetine [107][108][109][110]. Indeed, some studies have demonstrated the usefulness of crocin tablets in conjunction with imipramine or fluoxetine [111]. ...
The spice saffron is made from the dried stigmas of the plant Crocus sativus L. The main use of saffron is in cooking, due to its ability to impart colour, flavour and aroma to foods and beverages. However, from time immemorial it has also been considered a medicinal plant because it possesses therapeutic properties, as illustrated in paintings found on the island of Santorini, dated 1627 BC. It is included in Catalogues of Medicinal Plants and in the European Pharmacopoeias, being part of a great number of compounded formulas from the 16th to the 20th centuries. The medicinal and pharmaceutical uses of this plant largely disappeared with the advent of synthetic chemistry-produced drugs. However, in recent years there has been growing interest in demonstrating saffron's already known bioactivity, which is attributed to the main components-crocetin and its glycosidic esters, called crocins, and safranal-and to the synergy between the compounds present in the spice. The objective of this work was to provide an updated and critical review of the research on the therapeutic properties of saffron, including activity on the nervous and cardiovascular systems, in the liver, its antidepressant, anxiolytic and antineoplastic properties, as well as its potential use as a functional food or nutraceutical.
... In recent years, various animal studies have shown its medicinal properties such as antioxidant [11][12][13], anti-tumorigenic [12,[14][15][16], memory enhancer [17], antidepressant, anxiolytic, hypnotic [18][19][20][21], positive effect on sexual function [22], genoprotective [23,24], antitussive [25], cardioprotective [26][27][28][29], hepatoprotective [30], gastroprotective [31], antinociceptive [32] neuroprotective [33][34][35][36][37], anti-platelet [38], lipid-regulating, anti-atherogenic [39][40][41], anti-inflammatory [42], insulin resistance improvement [43], anticonvulsant [35], tracheal smooth muscle relaxant [44], b-adrenoceptor stimulator [45] and anti-histaminergic effects [46]. Antidepressant [47,48], anti-Alzheimer [49], antipruritic [50], improvement of erectile dysfunction [51] and premenstrual syndrome [52] are some saffron medicinal properties that have been proved in several clinical trials. In addition, saffron and its active ingredients attenuated the toxicity of natural and chemical agents [53]. ...
Saffron as a medicinal plant has many therapeutic effects. Phytochemical studies have reported that saffron is composed of at least four active ingredients which include crocin, crocetin, picrocrocin and safranal. The carotenoids of saffron are sensitive to oxygen, light, heat and enzymatic oxidization. However, regulation of these factors is required for saffron quality. Some pharmacologic effects of saffron and its active compounds include cardioprotective, neuroprotective, memory enhancer, antidepressant and anxiolytic. Among more than 150 chemicals of saffron, the most biologically active components are two carotenoids including crocin and crocetin. Most of the pharmacokinetic studies are related to these compounds. The pharmacokinetic studies have shown that crocin is not available after oral administration in blood circulation. Crocin is converted to crocetin in intestine but after intravenous injection, the level of crocetin in plasma is low. Crocetin can distribute in different tissues because of weak interaction between crocetin and albumin. Also it can penetrate blood-brain barrier and reach CNS by passive transcellular diffusion; thus it can be effective in neurodegenerative disorders. The large portion of crocin is eliminated via feces.
... Clinical studies concluded that saffron extracts (30 mg daily for 6 weeks) improve mild-to-moderate depression in patients compared to placebo, and were as effective as the antidepressant drugs imipramine and fluoxetine (Akhondzadeh, Fallah-Pour, Afkham, Jamshidi, & Khalighi-Cigaroudi, 2004Nourbala, Tahmasebipour, Akhoundzadeh, Khani, & Jamshidi, 2004). Further evidence for potential usefulness in BPSD was suggested as the component safranal was anxiolytic and hypnotic in vivo (Hosseinzadeh & Noraei, 2009). ...
Alzheimer's disease (AD) is reaching epidemic proportions yet treatment strategies are limited and are restricted to providing symptomatic relief for the cognitive and behavioral and psychological symptoms of dementia (BPSD). Chinese herbal medicine (CHM) has been a valuable source of medicines for centuries and research has burgeoned in recent years to understand the scientific basis for their use. Some plants have been used in CHM for AD symptoms (e.g., Polygala tenuifolia), while others are CHMs for different conditions, but they show mechanistic effects relevant to AD (e.g., Salvia miltiorrhiza). Some CHMs (e.g., Ginkgo biloba extract, and huperzine A from Huperzia serrata) show pharmacological activities relevant to AD, and promising effects on cognitive functions in clinical trials. Other CHMs show effects relevant to BPSD (e.g., Crocus sativus). This chapter discusses available scientific evidence for CHM plants and formulae that have been used both traditionally for AD, and those that have been used traditionally but not specifically for AD symptoms, and encompasses chemical, pharmacological and clinical studies. The ethnopharmacological approach to understanding the use of CHMs for AD is also discussed.
... These uses have been described in the traditional literature from different cultures over centuries [2] and have been identified in the past few years by systematic studies. While the anticancer effects are only related to in vitro and animal experiments (for reviews, see [1], [3]), the antidepressive properties of saffron extracts have been shown at 30 mg/day in two placebocontrolled preliminary phase II studies with n = 30 and 40 patients, respectively [4], [5]. The effects measured were comparable to those induced by fluoxetine and imipramine. ...
Extracts from saffron are used for treatment of cancer and depression. Because of known quality problems HPLC methods on RP18 2.5µm and monolitic RP18 material were developed for quality control including the quantification of crocins 1 to 5, crocetin, picrocrocin and the degradation products cis-crocins. A GC-MS method allowed detection and quantification of the volatile compounds from saffron pentane extract. Both systems together allowed comprehensive characterization of saffron herbal material and extracts for clinical/preclinical trials. Based on a wide analytical survey of saffron from the global market a specification for high-quality saffron of >20% crocins, >6% picrocrocin and not less than 0.3% of volatiles, calculated as sum of safranal, isophorone and ketoisophorone, was developed.
Because no detailed pharmacological effects are available to explain the clinical effects of saffron for treatment of cancer and depression receptor binding studies were performed. Saffron extracts and crocetin had clear binding capacity at the PCP binding side of NMDA receptor and at the sigma-1 receptor, while the crocin isomers and picrocrocin were not effective. These data give biochemical support for the above mentioned pharmacological effects of saffron.
... [7][8][9] A number of treatment approaches have been applied as MDD remedies. 10,11 Among those, antidepressant agents have the most consumption, 9,12 but their adverse effects may cause intolerance or inadequate responses in patients, decreasing their compliance. 13 Selective serotonin reuptake inhibitors (SSRIs) -the most frequent and popular antidepressants -have a widespread use in treatment of many psychiatric disorders. ...
... These uses have been described in the traditional literature from different cultures over centuries [2] and have been identified in the past few years by systematic studies. While the anticancer effects are only related to in vitro and animal experiments (for reviews, see [1], [3]), the antidepressive properties of saffron extracts have been shown at 30 mg/day in two placebocontrolled preliminary phase II studies with n = 30 and 40 patients, respectively [4], [5]. The effects measured were comparable to those induced by fluoxetine and imipramine. ...
... In clinical trials of saffron, with positive outcomes for cognition in Alzheimer's disease [70,71], premenstrual stress [72] and depression [73,74], a daily dose of 30 mg was used over days and weeks. In a clinical trial of saffron in age-related macular degeneration (AMD), with strongly positive outcomes [18,19], a daily dose of 20 mg was used, for over a year. ...
Background: Dietary saffron and photobiomodulation (low-level infrared radiation, PBM) are emerging as therapeutically promising protectants for neurodegenerative conditions, such as the retinal dystrophies. In animal models, saffron and PBM, given in limited daily doses, protect retina and brain from toxin- or light-induced stress. This study addresses the rate at which saffron and PBM, given in daily doses, induce neuroprotection, using a light damage model of photoreceptor degeneration in Sprague Dawley (SD) rats. Results: Rats were raised in dim cyclic (12 h 5 lux, 12 h dark) illumination, treated with saffron or PBM for 2-10 d, and then exposed to bright damaging light (1,000 lux for 24 h). After 1 week survival, the retina was assessed for photoreceptor death (using the TUNEL reaction), for surviving photoreceptor damage (thickness of the outer nuclear layer) and for the expression of a stress-related protein GFAP, using immunohistochemistry. Preconditioning the retina with saffron or PBM reduced photoreceptor death, preserved the population of surviving photoreceptors and reduced the upregulation of GFAP in Müller cells. At the daily dose of saffron used (1 mg/kg), protection was detectable at 2 d, increasing to 10 d. At the daily dose of PBM used (5 J/cm² at 670 nm) protection was detectable at 5 d, increasing to 7-10 d. Conclusions: The results provide time parameters for exploration of the mechanisms and durability of the protection provided by saffron and PBM.
... Improvement in the spatial cognitive abilities following chronic cerebral hypoperfusion has been observed with crocin and saffron extract. A dose of 30 mg saffron per day as a potential neuroprotective agent significantly reduced mild to moderate depression scores on a standard rating scale compared to placebo [109]. This may be due to the antioxidative and radical scavenging properties of saffron in neurological disorders including depression and Alzheimer's disease [108,110]. ...
Saffron is an integral part of various traditional medicines containing several phytochemicals having disease preventing and health promoting properties. The antidepressant, cardio protective and chemopreventive properties of saffron can be attributed to its constinuent active phytochemicals and bioactive compounds like crocin, crocetin and safranal. Publicly available databases like NCBI-PubChem and ChEMBL have millions of bioactive compounds.This offers opportunity to mine the compound(s) of interest based on desired attributes in the therapeutic area of interest. The current review, attempts to identify potential of molecular basis of bioactive compounds of saffron.
... Improvement in the spatial cognitive abilities following chronic cerebral hypoperfusion has been observed with crocin and saffron extract. A dose of 30 mg saffron per day as a potential neuroprotective agent significantly reduced mild to moderate depression scores on a standard rating scale compared to placebo [109]. This may be due to the antioxidative and radical scavenging properties of saffron in neurological disorders including depression and Alzheimer's disease [108,110]. ...
Saffron is an integral part of various traditional medicines containing several phytochemicals having disease preventing and health promoting properties. The antidepressant, cardio protective and chemopreventive properties of saffron can be attributed to its constinuent active phytochemicals and bioactive compounds like crocin, crocetin and safranal. Publicly available databases like NCBI-PubChem and ChEMBL have millions of bioactive compounds. This offers opportunity to mine the compound(s) of interest based on desired attributes in the therapeutic area of interest. The current review, attempts to identify potential of molecular basis of bioactive compounds of saffron.
... [7][8][9] A number of treatment approaches have been applied as MDD remedies. 10,11 Among those, antidepressant agents have the most consumption, 9,12 but their adverse effects may cause intolerance or inadequate responses in patients, decreasing their compliance. 13 Selective serotonin reuptake inhibitors (SSRIs)-the most frequent and popular antidepressants-have a widespread use in treatment of many psychiatric disorders. ...
Background
Depression is the most common psychiatric disorder in the world. The conventional medications for depression, however, often have significant side effects. These adverse effects of conventional therapies, have motivated researchers to study alternative options including complementary and traditional treatments for solving the problem.
Objective
To compare the efficacy of Nepeta menthoides Boiss. & Buhse freeze- dried aqueous extract with sertraline in the treatment of major depression.
Design and setting
From April to September of 2015, 72 patients from two psychiatry clinics of Shiraz University of Medical Sciences who met the criteria for major depression based on the structured clinical interview as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, participated in a two-armed double-blind randomized controlled trial.
Intervention
Subjects were randomly assigned to receive Nepeta menthoides or sertraline for four weeks.
Outcome measures
Patients were evaluated in terms of the Beck Depression Inventory-II (BDI-II) total score and common side effects of medications at the base line, the second and fourth weeks, and two weeks following the intervention (i.e. in the sixth week).
Results
The mean changes in the Beck Depression Inventory scores in Nepeta menthoides group were significantly higher in terms of the BDI-II scores diminution as compared to that of the control (p ≤ 0.001). Two weeks follow up after intervention showed a lower recurrence rate in the Nepeta menthoides group. (p ≤ 0.001)
Conclusion
Nepeta menthoides may have potential benefits in the control of mood in patients suffering from major depression. Sustention of antidepressant effect and delay in the recurrence of depression could be considered worthwhile using this herb.
... Saffron is derived from the plant Crocus sativus, and has been used in traditional Indian medicine for centuries as an analgesic and to treat cognitive dysfunction and mental illness [46,47]. Several rigorous modern studies have highlighted its potent antioxidant [48,49], antiinflammatory [50,51], anxiolytic [52], antidepressant [53][54][55], anti-carcinogenic [56][57][58], antihypertensive [59,60], anti-obesity [61][62][63] and anti-diabetic [64][65][66] effects. For example, oral saffron was found to have a similar effect as the known antidepressant drug fluoxetine, in patients with mild to moderate depression [67]. ...
Age-related disorders of the central nervous system such as Alzheimer’s disease, Parkinson’s disease and retinal degenerations are debilitating conditions that pose major health, economic and social problems. Current treatments for these conditions have failed to provide fully effective treatments for the condition.
Detrimental oxidative changes that are associated with metabolic activities affect the brain and cognitive function over time and tend to lead to the onset of dementia and several other neurodegenerative diseases. Over the past decade, extensive epidemiological studies have shown significant associations of regular phytochemical consumption of fruits, vegetables, tea leaves with health improvements as well as reduced risk for cardiovascular disease, stroke, diabetes, some cancers, and neurodegenerative diseases.
In this review, evidence is presented to show that increased levels of oxidative stress leads to the aging and neurodegenerative process, and dietary saffron, a potent antioxidant, could be beneficial to combat the debilitating disorders of the central nervous system. Beneficial actions of antioxidant saffron include anti-carcinogenic, anti-depressant, anti-inflammatory, anti-hypertensive, anti-diabetic and anxiolytic effects; and these beneficial effects have been demonstrated to contribute to improvements in cellular integrity and function in animal and human studies. However, the mechanism of action of saffron is yet to be completely understood and this needs to be further explored.
... Dále šafrán obsahuje žluté barvivo krocin, což je směs glykosidů karotenoidu krocetinu, a aromatické látky, zejména monoterpenoidy (21). Extrakt z blizen má antidepresivní účinek, účinnost při léčbě lehké a středně těžké deprese byla potvrzena v dvojitě slepé placebem kontrolované studii (22). Krocin pravděpodobně působí jako inhibitor zpětného vychytávání dopaminu a noradrenalinu, safranal působí jako inhibitor zpětného vychytávání serotoninu. ...
Mood disorders, mainly depression, are nowadays one of the most frequent mental illnesses. Although there are many antidepressants with different mechanism of action on the market, in cases of mild depression herbal remedies can be used. The article describes selected plants with antidepressant effect - Hypericum perforatum, Sceletium tortuosum, Panax ginseng, Rhodiola rosea, Magnolia and Crocus sativus. Some of them are already used in the therapy, others may be used in the future. Some plants are available for sale as dietary supplements.
... The dried saffron (Crocus sativus L.) stigma was purchased from Novin Zaferan Co (Mashhad, Iran) and was identified by the Department of Cultivation and Development of Institute of Medicinal Plants, Tehran, Iran. The stigma extract was prepared using the procedure as described by Akhondzadeh et al. (2005). In brief, 120 g of dried and milled stigmas were extracted with 1800 mL ethanol (80%) by percolation procedure in three steps then the solvent was removed by evaporation at a temperature of 35-40°C. ...
The effects of the natural food saffron (90 mg/d) on exercise induced sperm DNA damage, antioxidative and peroxidative biomarkers and seminological profile in male road cyclists were evaluated. Twenty-four healthy nonprofessional cyclists (aged 17–26 years) were randomly assigned to exercise + Saffron (EX + SAF, n = 12) and exercise (EX, n = 12) groups for an experimental period of 16 weeks. After the intervention, the number of terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling (TUNEL)-positive sperm cells and peroxidative biomarkers increased, while antioxidative biomarkers and seminological profile decreased in the EX group. These changes were significantly attenuated in the EX + SAF group. Moreover, for both groups the observed changes in peroxidative and antioxidative biomarkers could be correlated positively and negatively, respectively, with sperm DNA fragmentation. Saffron, rich in carotenoids, flavonoids and vitamins, is therefore a potentially potent functional food for preventing exercise-induced sperm DNA damage, at least in part, through optimizing oxidant/antioxidant equilibrium and attenuation of oxidative stress.
... The lack of predictability of the efficacy of a particular treatment mirrors the mystery surrounding the etiology of the condition [4]. Over the last decade evidence based herbal medicine in the treatment of psychiatric disorders and dermatological disease, has been considered [6][7][8][9][10][11][12][13][14][15]. There are some natural remedies that are being explored for the treatment of aphthae [16,17]. ...
Background: It has been reported that curcumin has anti inflammatory, antibacterial, anti tumor and analgesic properties. Objective: The purpose of this study was to investigate the efficacy of curcumin in the treatment of minor aphthous stomatitis. Methods: The study was a two week, randomized, double blind, placebo controlled of patients with minor aphthous. Patients between 18 and 65 years old were included if they presented with 1-5 aphthous ulcers of less than 24 h duration. Twenty-eight patients were randomly allocated to curcumin gel containing (2% curcumin) and 29 patients were allocated to placebo gel for a two week, double-blind, placebo-controlled study. The patients used the medication using a swap twice per day. After enrolment, the size of ulcers were measured by the investigator, and pain was evaluated by the patients based on Perceived Pain Rating Scale before drug application (day 0) and at days 4, 7, and 14. Patients overall satisfaction were assessed at the end of treatment. Results: Curcimin gel significantly reduced pain intensity and size of aphthous ulcer compare to placebo. Significant group differences appeared at the end of the trial regarding overall satisfaction of the patients. Conclusion: The results of present study provide evidence that curcumin gel is a well tolerated effective treatment modality for minor aphthous stomatitis.
... There are a number of herbal remedies for treatment of depression and PMS in women and the most famous one is saffron. In addition, there are a number of herbal remedies for treatment of primary dysmenorrheal [15][16][17][18][19][20][21]. ...
Dysmenorrhea is called "primary" when there is no specific abnormality and "secondary" when the pain is caused by an underlying gynecological problem. It is believed that primary dysmenorrhea occurs when hormone-like substances called "prostaglandins" produced by uterine tissue trigger strong muscle contractions in the uterus during menstruation. However, the level of prostaglandins does not seem to have anything to do with how strong a woman's cramps are. Some women have high levels of prostaglandins and no cramps, whereas other women with low levels have severe cramps. This is why experts assume that cramps must also be related to other things (such as genetics, stress, and different body types) in addition to prostaglandins. Secondary dysmenorrhea may be caused by endometriosis, fibroid tumors, or an infection in the pelvis. In this article we focus on herbal medicine in the treatment of primary dysmenorrheal.
... Another group of studies evaluated the therapeutic effect of saffron (or its active components) in different clinical conditions. The results of these studies mostly indicated safety of using these products in patients with ischemic heart diseases, depression, mild to moderate Alzheimer's disease or sexual dysfunction (Akhondzadeh et al. 2005, Cai et al. 2013, Shahmansouri et al. 2014). According to our literature survey, there was no report about using saffron products in patients with mental illnesses, especially schizophrenia. ...
Objectives:
Saffron is the stigma of Crocus sativus L., which has the potentials to play a role in the treatment of many diseases. Although many researches are now going on this precious spice, there are few data on saffron safety in human, especially in patients with chronic mental illnesses. This study aimed to evaluate the short-term safety and tolerability of both saffron and crocin (its major constituent) in adult patients with schizophrenia.
Materials and methods:
The capsules of saffron aqueous extract (SAE) and crocin were used to evaluate short-term safety and tolerability in patients with schizophrenia. A double-blind, placebo-controlled study was performed on patients with schizophrenia. The patients were all male and were divided into three 22-patient groups. While receiving their normal treatment, they also received a 12 week treatment with SAE (15 mg twice daily), crocin (15 mg twice daily) or placebo.
Results:
A total of 61 patients completed the trial; none of them reported a serious side effect. WBC count increased significantly in patients receiving saffron aqua extract (SAE), but it was within the normal range and had no clinical significance. Other hematologic components, markers of thyroid, liver and kidney or inflammation markers had no statistically significant difference among the groups.
Conclusion:
This study showed that SAE and crocin in doses of 15 mg twice daily were safely tolerated in patients with schizophrenia.
... According to some research works, saffron can be used as a valuable agent in the treatment of depression. Proverbially , administration of saffron extract resulted in significant decrease in depression symptoms (Akhondzadeh et al., 2005). Another work reported that saffron has a similar performance in treatment of depression (Noorbala et al., 2005). ...
Depression is a serious and prevalent mental disorder as well as a leading cause of disability. Natural herb products may be considered as an alternative to synthetic antidepressants with fewer side effects and more tolerability. Several clinical and animal studies showed that saffron, the stigmas of Crocus sativus L., may be one of the best supplements for depressive disorders. Among more than 150 chemicals in saffron, 2 carotenoids including crocin and crocetin and monoterpene aldehydes such as safranal are the most biologically active components. Saffron and its main constituents exhibit antioxidant, anti-inflammatory, anticancer, anticonvulsant, antigenotoxic, antitussive, etc. In this chapter, different studies which investigated the antidepressant effects of C. sativus L. and its main ingredients as well as proposed mechanisms have been introduced.
Oxidative stress has been related to osteoporosis and other pathologies at the bone. Coenzyme Q10 (CoQ10), a lipid-soluble antioxidant present in cell membranes, has been suggested in vitro to reduce intracellular reactive oxygen species (ROS) production at the same time to prevent or reduce osteoclastogenesis. Also, it promotes osteoblast differentiation and proliferation and matrix mineralization. Thus it has been suggested that this effect on osteoclastogenesis could be a consequence of the reduction of intracellular ROS. The protective effect of CoQ10 against bone loss has been also demonstrated in rodents. Age-associated changes in systemic markers of oxidative damage in animals treated with CoQ10 suggest that this antioxidant can reduce not only intracellular ROS alleviating oxidative damage but also osteoclastogenesis and bone resorption triggered by different signals. Additionally, it has been suggested that oxidative stress is the main mechanism explaining bone alterations both in aged rodents and in those with acute sex steroid deficiency.
Ethnopharmacological relevance:
The research into bioactive natural products originating from medicinal plants, fungi and other organisms has a long history, accumulating abundant and diverse publications. However no quantitative literature analysis has been conducted.
Aim of the study:
Here we analyze the bibliometric data of ethnopharmacology literature and relate the semantic content to the publication and citation data so that the major research themes, contributors, and journals of different time periods could be identified and evaluated.
Materials and methods:
Web of Science (WoS) was searched to identify relevant publications. The Analyze function of WoS and bibliometric software (VOSviewer) were utilized to perform the analyses.
Results:
Until the end of November 2018, 59,576 publications -linked to 'ethnopharmacology' indexed by WoS, published since 1958 in more than 5,600 journals, and contributed by over 20,600 institutions located in more than 200 countries/regions, were identified. The papers were published under four dominating WoS categories, namely pharmacology/pharmacy (34.4%), plant sciences (28.6%), medicinal chemistry (25.3%), and integrative complementary medicine (20.6%). India (14.6%) and China (13.2%) were dominating the publication space. The United States and Brazil also had more than 8.0% contribution each. The rest of the top ten countries/regions were mainly from Asia. There were around ten-fold more original articles (84.6%) than reviews (8.4%).
Conclusions:
Ethnopharmacological research has a consistent focus on food and plant sciences, (bio)chemistry, complementary medicine and pharmacology, with a more limited scientific acceptance in the socio-cultural sciences. Dynamic global contributions have been shifting from developed countries to economically and scientifically emerging countries in Asia, South America and the Middle East. Research on recording medicinal plant species used by traditional medicine continues, but the evaluation of specific properties or treatment effects of extracts and compounds has increased enormously. Moreover increasing attention is paid to some widely distributed natural products, such as curcumin, quercetin, and rutin.
Objective:
A herbal combination (saffron extract, passion flower herb extract, cocoa seed extract, radish extract and black cumin extract) called "Relief" was designed as a supportive therapy of alcohol withdrawal syndrome (AWS). This combination was based on the scientific evidence of each constituent effect on AWS-like symptoms. In addition, our preclinical studies have shown the effectiveness of Relief on AWS detoxification. The rationale of the study was to document whether the oral intake of the designed content of Relief could have a positive effect on the course of alcohol detoxification by reducing some of the AWS in hospitalized patients.
Methods:
This pilot study was performed as non-interventional, open, single-armed, prospective on 32 hospitalized patients entered for detoxification of alcohol withdrawal syndrome. Each patient received daily three capsules of Relief for 15 days, and AWS parameters were monitored, in addition to serum liver enzymes and quality of life which was evaluated using the Befindlichkeits-Skala (Bf-SR) scaling system.
Results:
Relief administration significantly reduced the percentage of patients with hyperhidrosis (r=0.815, p<0.001), reduced serum liver enzymes by ~50-80% (p<0.05), and increased normalization of appetite (r=0.777, p<0.001). Besides, before the treatment began the Bf-SR scale was 28.3±4.3, which was typical for neurological syndromes such as depression or insomnia, and during Relief administration the Bf-SR scale significantly dropped to 15.6±2.4 (p<0.001). As for the safety, four, but not serious, adverse events were observed; two of them may be product related. Finally, 84.4% of patients' assessed Relief treatment as good to excellent and 87.5% of the patients declared an interest in reusing Relief for the next detoxification period.
Conclusions:
Despite the limitations of the present study, the findings showed the potential of Relief for the improvement of the clinical situation of patients with symptoms of alcohol withdrawal and therefore, justify a full-scale well-controlled study design to be implemented.
Anxiety and depression are prevalent among cancer patients, with significant negative impact. Many patients prefer herbs for symptom relief to conventional medications which have limited efficacy/side effects. We identified single-herb medicines that may warrant further study in cancer patients. Our search included PubMed, Allied and Complementary Medicine, Embase, and Cochrane databases, selecting only single-herb randomized controlled trials between 1996 and 2016 in any population for data extraction, excluding herbs with known potential for interactions with cancer treatments. One hundred articles involving 38 botanicals met our criteria. Among herbs most studied (≥6 randomized controlled trials each), lavender, passionflower, and saffron produced benefits comparable to standard anxiolytics and antidepressants. Black cohosh, chamomile, and chasteberry are also promising. Anxiety or depressive symptoms were measured in all studies, but not always as primary endpoints. Overall, 45% of studies reported positive findings with fewer adverse effects compared with conventional medications. Based on available data, black cohosh, chamomile, chasteberry, lavender, passionflower, and saffron appear useful in mitigating anxiety or depression with favorable risk–benefit profiles compared to standard treatments. These may benefit cancer patients by minimizing medication load and accompanying side effects. However, well-designed larger clinical trials are needed before these herbs can be recommended and to further assess their psycho-oncologic relevance.
Anxiety disorders belong to most frequently encountered mental disorders in general, since up to 25 % of the population suffers by a clinically important anxious disorder at least once in a lifetime. Anxiolytics and antidepressants are particularly used to treat anxiety. and insomnia is treated with sedatives and hypnotics. There are a number of products for the treatment of the anxiety, but in benzodiazepine-group anxiolytics, there is a risk of the tolerance and addiction development. Thus, a great attention is being paid to the investigation of new medicines without these side effects. There are a number of plants, which have been traditionally used for the treatment of anxiety and insomnia and these effects are frequently supported by modern trials. Herbaceous products are frequently used even at the time being, particularly for the treatment of mild problems. Tea mixtures, tinctures, food supplements and registered medicinal products containing extracts from plants are used. Further research of effects of these plants and their components can offer new pharmaceuticals. In the article presented here, there is an outline of main plants used in the treatment of anxiety and insomnia. The first part of the article is aimed at our original plants and plants cultivated in our country (Cannabis sativa, Coriandrum sativum, Crocus sativus, Eschscholzia californica, Ginkgo biloba, Humulus lupulus, Hypericum perforatum, Lavandula angustifolia, Magnolia officinalis and M. obovata, Matricaria recutita, Melissa officinalis, Rhodiola rosea, Scutellaria spp., Tilia americana and Valeriana officinalis), and the second part deals with exotic plants (Atractylodes macrocephala, Bacopa monnieri, Centella asiatica, Citrus spp., Clitoria ternatea, Echium amoenum, Erythrina mulungu, Morinda citrifolia, Myristica fragrans, Ocimum sanctum, Panax ginseng and P. quinquefolius, Passiflora incarnata, Piper
methysticum, Sceletium tortuosum, Withania somnifera, Zingiber officinale and Ziziphus jujuba).
Carotenoids are a class of more than 600 secondary metabolites occurring in plants,algae, and photosynthetic bacteria; their flat, long C40 system of alternating double andsingle bonds allow them to be the sources of the yellow, orange, and red colours of manyplants, including fruit and vegetables, where they are believed to contribute to the overallphotosynthetic processes. They are important in human nutrition as a source of vitaminA, and act as preventive agents against cancer and heart disease. Furthermore, they areimportant precursors of several compounds responsible for the flavour and fragrance offoods and flowers. Carotenoids are also the most characteristic and important componentsof saffron (Crocus sativus L.) stigmas, directly responsible for the particular colorantfeatures of this spice, as well as precursors of compounds responsible for its bitter tasteand aroma. Saffron carotenoids include fat-soluble components such as licopene, β-carotene and zeaxanthin, but also and mainly, a peculiar class of molecules, the C20 apocarotenoidcrocetin (8,8'-diapo-8,8'-carotenedioic acid) and its ester derivatives, with oneor more sugar moieties, which lend these compounds the peculiar characteristic to be thesole water-soluble components among the carotenoids - the trans-crocetin (β-Ddigentibiosyl)ester being the most important and abundant component of this class.Crocetin and its related compounds have so far been detected only in some Crocusspecies, in Gardenia jasminoides Ellis, Artocarpus hetrophyllus Lam. (jackfruit), Coleusforskolii (Willd.) Briq., Jacquinia angustifolia L., Buddleja officinalis Maxim., and Nyctanthes arbortristis L. (night flowering jasmine). The peculiar chemical structure ofsaffron apocarotenoids gives them particular characteristics in terms of chemical/physicalreactivity and solubility; furthermore, this pool of metabolites are apparently responsiblefor the biological properties ascribed to this spice so far: antioxidant, antitumor andmemory effects enhancer, to list some of them. A detailed review on this particular andunique class of carotenoids will be given, together with some biosynthetic discussion andthe latest scientific discoveries on their biological activities.
Saffron is a flowering plant used as a spice and food colorant. It has been used in traditional medicine for various purposes, such as an analgesic, sedative, expectorant, antidepressant, antispasmodic, aphrodisiac, digestive, and carminative. Saffron contains several active components, such as crocetin, crocin, and safranal. In this chapter, we have summarized the neuropharmacological effects of saffron, crocin, croetin, and safranal in the peripheral and central nervous system. Saffron and its active constituents have shown several important effects including antidepressant, antinociceptive and anti-inflammatory, anxiolytic, hypnotic, and cytoprotective effects in animal studies. Also, saffron has protective effects in reducing opioid withdrawal syndrome, neurodegenerative diseases such as epilepsy disorder, brain ischemia, Parkinson's disease, and memory impairment. Furthermore, in clinical studies saffron has shown significant effects in treatment of depression, Alzheimer's disease, and age-related macular degeneration. Further studies are needed to provide clinical evidence on the beneficial effects of saffron for treatment of neurological disorders.
Cognition involves various complex functions such as learning, memory, perception, psychomotor functions etc. In recent years, exploration of novel phytonutrients for treating cognitive impairments associated with aging as well as neurodegenerative diseases have attracted wide attention. Currently the focus in this area of research is on various drug targets including cholinergic receptors, serotonergic receptors, histaminergic receptors and molecules that can modulate gene expression which significantly modulate the process of memory. However, the occurrence of adverse effects such as addiction and other undesirable neuropsychiatric complications resulting from the use of conventional drugs have necessitated the search for alternative/complementary approaches which have resulted in an increased demand for natural molecules. Phytochemicals which alleviate oxidative stress modulate signalling pathways as well as synaptic plasticity and thus maintain energy homeostasis can be potential candidates for cognitive 290 RPMP Vol. 42—Nutraceuticals and Functional Foods enhancement. In this Chapter, the basic mechanism of learning and memory; the proposed drug targets; plants and plant derived cognitive enhancers and the mechanisms by which phytonutrients act on these drug targets have been reviewed.
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