Saffron (Mood)

Saffron is the dried stigma of Crocus sativus L. flowers. The yellow-orange color of saffron comes from crocin, a water-soluble carotenoid that can be ingested. Crocin is known for its anti-inflammatory and antioxidant potential. It is believed to affect inflammation and oxidative stress, making it a promising therapeutic option. However, research on its impact is inconclusive. This meta-analysis aimed to assess the benefits of crocin supplementation and its specific effects on inflammation and oxidative stress markers. A comprehensive search of the literature was conducted up to February 2024 in PubMed/Medline, Scopus, and Web of Science to find suitable randomized clinical trials (RCTs). All participants were adults who were supplemented with crocin as part of the study intervention. The selected trials were subjected to heterogeneity tests using the I 2 statistic. Random effects models were examined based on the heterogeneity tests, and the pooled data were calculated as weighted mean differences (WMD) with a 95% confidence interval (CI). Of the 519 papers that remain after duplications were removed, 13 eligible RCTs were included in the present meta-analysis. Our findings indicated that crocin supplementation significantly reduced c-reactive protein (CRP) levels (SMD: -0.50; 95%CI: -0.86 to -0.13; p = 0.008), tumor necrosis factor-α (TNF-α) (SMD: -1.96; 95%CI: -2.72 to -1.19; p < 0.001), and interleukin-6 (IL-6) (SMD: -3.52; 95%CI: -6.84 to -0.20; p = 0.03). Also, crocin supplementation led to a significant increase in total antioxidant capacity (TAC) (SMD: 1.48; 95%CI: 0.52 to 2.43; p = 0.002). Overall effect size showed that crocin intake failed to change the erythrocyte sedimentation rate (ESR) and malondialdehyde (MDA) levels significantly. Crocin reduces inflammatory markers and increases TAC. The effect of crocin on inflammatory markers was greater in a dose ≥ 30 mg/day and an intervention duration ≥ 12 weeks. However, more studies are needed for definitive conclusions. © 2024 John Wiley & Sons Ltd.

OBJECTIVES: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations. METHODS: The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence - meta-analysis or two or more RCTs - due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the 'level of evidence' (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was 'Recommended' (+++), 'Provisionally Recommended' (++), 'Weakly Recommended' (+), 'Not Currently Recommended' (+/-), or 'Not Recommended' (-) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed. RESULTS: Amongst nutraceuticals with Grade A evidence,

Several pharmaceutical and non-pharmaceutical approaches have been suggested to improve liver health. There is a large discrepancy in the effects of saffron supplementation on liver function in adults. To fill this knowledge gap, this systematic review and meta-analysis of randomized controlled trials (RCTs) assess the effects of saffron supplementation on liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A systematic search current to August 2020 was performed in PubMed/Medline, Scopus, Web of Science, and Google Scholar using relevant keywords to detect eligible articles. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). Nine eligible trials were included in the final analysis. The pooled analysis revealed that serum ALT concentrations were significantly reduced using saffron compared to placebo (WMD: -2.39 U/L; 95% CI: -4.57 to -0.22; P = 0.03, I2= 87.9%, P < 0.001). However, saffron supplementation did not affect levels of serum AST (WMD: 1.12 U/L; 95% CI: -1.42 to 3.65; P = 0.39) or ALP (WMD: 4.32 U/L; 95% CI: -6.91 to 15.54; P = 0.78). In the dose-response analysis, we did not find a significant dose-response relationship between dosage and duration of saffron supplementation on serum levels of ALT, AST, and ALP. We found that saffron supplementation can reduce ALT serum concentrations without significant effects on other liver function indicators, including AST and ALP. Nevertheless, future large RCTs on diverse populations are needed to understand better the effects of saffron and its constituents on these enzymes.

The effect of saffron supplementation on subclinical inflammation remains inconclusive. We performed a systematic review and meta-analysis to summarize available findings on the effect of saffron supplementation on inflammatory biomarkers (C-reactive protein [CRP], tumor necrosis factor-α [TNF-α], and interleukin-6 [IL-6]) in adults. We searched PubMed/Medline, Scopus, Web of Science, and Google Scholar databases up to November 2019 using relevant keywords to identify eligible trials. All randomized controlled trials (RCTs) that examined the effect of oral saffron supplementation on plasma concentrations of CRP, TNF-α, and IL-6 were included. For each outcome, mean differences and SDs were pooled using a random-effects model. Overall, eight RCTs were included in this meta-analysis. The pooled results showed that saffron supplementation did not result in significant changes in serum CRP (weighted mean difference [WMD]: -0.43 mg/L; 95% confidence interval [CI]: -1.04 to 0.17; p = .16), serum TNF-α (WMD: -1.29 pg/mL; 95% CI: -4.13 to 1.55; p = .37), and IL-6 concentrations (WMD: 0.11 pg/mL; 95% CI: -0.79 to 1.00; p = .81). Subgroup analysis indicated a significant reduction in serum CRP levels in studies with baseline CRP of ≥3 mg/L, saffron dosage of ≤30 mg/day, and intervention duration of <12 weeks, as well as trials that used crocin. Similarly, saffron was found to decrease TNF-α in studies that recruited non-diabetic subjects, subjects with baseline levels of ≥15 pg/mL, and participants with <50 years old, as well as trials that administered saffron at the dosage of ≤30 mg/day. We also found a significant non-linear effect of saffron dosage on serum CRP concentrations (pnon-linearity = .03). The overall results indicated that saffron supplementation did not affect inflammatory cytokines. Further high-quality studies are needed to firmly establish the clinical efficacy of supplemental saffron on inflammatory biomarkers. © 2020 John Wiley & Sons, Ltd.

BACKGROUND: The findings of trials investigating the effects of saffron (Crocus sativus L.) supplementation on depression, anxiety, and C-reactive protein (CRP) are inconsistent. The current meta-analysis of randomized controlled trials (RCTs) was carried out to assess the effects of saffron (Crocus sativus L.) administration on mental health parameters and CRP levels. METHODS: Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until 30th July 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. RESULTS: Twenty one trials were included in this meta-analysis. Consumption of saffron resulted in a significant reduction in Beck Depression Inventory (BDI) (11 studies with 12 effect size) (WMD: -4.86; 95 % CI: -6.58, -3.14), Beck Anxiety Inventory (BAI) (5 studies) (WMD: -5.29; 95 % CI: -8.27, -2.31) and Pittsburgh Sleep Quality Index (PSQI) scores (3 studies with 4 effect size) (WMD: -2.22; 95 % CI: -2.73, -1.72). Saffron intake did not affect Hamilton Depression Rating Scale (HDRS-D), Hamilton Anxiety Rating Scale (HARS-A) scores and C-reactive protein (CRP) levels. CONCLUSIONS: This meta-analysis demonstrated that saffron intake significantly reduced BDI, BAI and PSQI scores, but did not affect HDRS-D, HARS-A scores and CRP levels.

BACKGROUND: Subclinical depressive symptoms, including low mood, fatigue and anxiety, refer to clinically relevant depressive manifestations that do not meet the criteria for major depressive disorder. These symptoms affect quality of life and can lead to chronic mental health issues. Nutritional interventions, such as saffron extract supplementation, may help modulate mood and inflammation, potentially alleviating these symptoms. OBJECTIVES: This study evaluated the efficacy of a 6-wk saffron extract supplementation on mood in healthy individuals with subclinical neuropsychiatric symptoms and explored the underlying mechanisms. METHODS: This randomized, double-blind, placebo-controlled study involved 51 adult healthy individuals who received oral administration of either saffron extract or a placebo for 6 wk. The primary outcome was a composite z-score averaging standardized scores of depression (Beck Depression Inventory-II), anxiety (State-Trait Anxiety Inventory-YA), and fatigue (Multidimensional Fatigue Inventory 20). Secondary outcomes included neuropsychiatric scores, quality of life, inflammatory markers, and hypothalamic-pituitary-adrenal axis reactivity. Amino acid derivatives were analyzed in blood samples. RESULTS: Saffron extract did not significantly affect the primary outcome of combined depressive, anxiety, and fatigue symptoms (z-score) nor individual symptoms. However, it improved autoperceived mental health, as reflected in increased mental health scores over time on the Medical Outcome Study Short-Form 12 questionnaire, compared with placebo (mean at 6 wk: 53.8 ± 12.7 vs 44.6 ± 11.4 for placebo and saffron group, respectively; time × treatment, P = 0.04). There were no significant effects on inflammatory parameters or hypothalamic-pituitary-adrenal axis reactivity. Metabolomic analysis revealed that saffron extract significantly modulated N-acetyl-phenylalanine. CONCLUSIONS: Saffron extract supplementation do not affect subclinical depressive symptoms, either as a composite score or individual symptom categories. A potential effect on improved mental health outcomes cannot be excluded but requires further replication in future well-powered tr

BACKGROUND: Saffron, derived from the stigmas of the Crocus sativus flower, has been shown in previous trials to have antidepressant effects in clinically diagnosed adults. However, the recruitment of small sample sizes, short treatment periods, and variability in the quality of studies have negatively impacted the strength of conclusions. OBJECTIVES: The purpose of this 2-arm, 12-wk, parallel-group, randomized, double-blind, placebo-controlled trial was to examine the effects of supplementation with a saffron extract (Affron) on mood and sleep in adults experiencing subclinical depressive symptoms. METHODS: Two hundred and two adults aged 18-70 with depressive symptoms were supplemented with 28 mg saffron daily or a placebo. Outcome measures included the Depression, Anxiety, and Stress Scale - 21, Sleep Disturbance and Sleep-Related Impairment Scale, World Health Organization-Five Well-Being Scale, and daily depression, stress, and anxiety ratings. RESULTS: On the primary outcome measure, compared to the placebo, saffron was associated with greater improvements in the Depression, Anxiety, and Stress scale - 21 depression score (β: -2.92 points; 95% confidence interval: -5.13, -0.71 points; Cohen's d = 0.39), with 72.3% of participants in the saffron group achieving a clinically significant change (a reduction of ≥ 7 points) compared to 54.3% of participants in the placebo group (P = 0.010). However, in the other secondary outcomes, there was no evidence of between-group differences. In exploratory analyses across various strata and assumptions, improvements in sleep disturbances (β: -2.72 points; 95% confidence interval: -4.99, -0.46 points; Cohen's d = 0.44) were identified in a subset of participants with a greater severity of sleep disturbance. There were no serious adverse reactions reported. CONCLUSIONS: This study, the largest conducted to date on saffron, provides evidence supporting the beneficial effects of 3 mo of saffron supplementation on depressive symptoms in adults. Large placebo responses were evident in this study, which require consideration in future trials. This trial was registered at Australian and New Zealand clinical trials registry as A

Background/Objectives: The global prevalence of mental health disorders, particularly anxiety and depression, has increased significantly, with rates further elevated by the COVID-19 pandemic. Conventional pharmacological treatments, while effective, often lead to side effects that can impact patient adherence and quality of life. This has driven interest in safer, natural adjunctive therapies. Crocus sativus L. (Iridaceae) (saffron) and Scutellaria baicalensis Georgi (Lamiaceae) (scutellaria) have individually shown potential, in humans and animals, respectively, as mood regulators, with bioactive compounds that modulate neurotransmitter systems and possess anti-inflammatory and anxiolytic effects. This study aimed (1) to explore the efficacy and safety of scutellaria extracts in humans and (2) to test a possible synergistic effect when combining scutellaria and saffron on mood regulation in individuals experiencing mild-to-moderate depressive symptoms. Methods: In a randomized, double-blind, placebo-controlled trial, 180 participants with mild-to-moderate depressive symptoms were assigned to receive either scutellaria extract alone (SCUTELL'UP®), saffron extract alone (SAFFR'ACTIV®), a combination of scutellaria and saffron extracts (SAFFR'UP®), or a placebo for six weeks. The primary outcome was assessed using a standardized depression scale (Beck Depression Inventory). The secondary outcomes, including anxiety, emotional state, well-being level, and sleep quality, were all assessed using validated questionnaires. Safety and tolerability were evaluated throughout the study period. Results: The results confirmed the beneficial effects of saffron extract on depressive and anxious symptoms, as well as its role in improving sleep quality. For the first time in humans, scutellaria extract demonstrated a positive effect on mood regulation. Furthermore, a synergistic effect of the combination of these two extracts was identified, leading to enhanced improvements in depressive and anxious symptoms and emotional well-being among individuals with mild-to-moderate depression, compared to the placebo group. Minimal adverse effects were reported across all treatment group

The study aimed to investigate the effects of acute ingestion of saffron (SAF) on physiological (i.e., heart rate and blood lactate) and perceptual (i.e., ratings of perceived exertion [RPE] and feeling scale) measures in response to a repeated-sprint ability test (RSS) in healthy young males (N = 22; mean ± SD: age, 21.7 ± 1.24 yrs.). All participants completed two experimental trials with a one-week washout period using a double-blind, placebo-controlled, crossover design. In each session, the participants were randomly chosen to receive either a capsule of saffron (300 mg) (SAF session) or a capsule of lactose (PLB session) two hours before performing the RSS.No significant differences (p > 0.05) were found for heart rate, RPE, and feeling scale between the SAF or PLB sessions at pre- and post-RSS. There were no significant changes (p > 0.05) in peak time, total time, fatigue index, and blood lactate in either the SAF or PLB sessions. Acute SAF ingestion did not significantly improve RSS performance nor physiological and perceptual measures in active young males. Future trials should address the topic by using shortened/prolonged higher doses of SAF on biological, physical, physiological, and perceptual responses to acute and chronic exercise. © 2024. The Author(s).

Crocin is the major active carotenoid of saffron (Crocus sativus L.). Its pluripotent effects have led to a growing body of literature investigating its antitumor properties as well as its diverse potentials for mood stabilization, normal tissue protection, and inflammation reduction; However, there is a gap in clinical trials testing this substance in cancer patients. In this randomized, double-blind, placebo-controlled clinical trial, patients with newly diagnosed esophageal squamous cell carcinoma were randomly assigned to either 30 mg/day of crocin or placebo, prescribed during the neoadjuvant chemo-radiotherapy. The primary endpoints were pathological response and toxicity, and secondary endpoints were depression and anxiety levels and survival analysis.

BACKGROUND: Multiple sclerosis (MS), as a demyelinating disease correlated with inflammation and oxidative stress, affects the central nervous system and causes a wide range of complications, including psychiatric disorders. Considering the anti-inflammatory and antioxidant properties associated with the bioactive components of saffron, such as crocin (trans-crocetin bis(β-d-gentiobiosyl) ester), and their potential impact on ameliorating psychiatric symptoms, our study aimed to investigate the effect of crocin on biomarkers of inflammation, oxidative stress, and mental health, e.g., depression and anxiety in individuals with MS. METHOD: Patients with MS were randomized into two groups, taking either 15 mg crocin tablets twice a day (n = 25; 30 mg/day) or placebo tablets (n = 25) for 8 weeks. The valid and reliable Beck depression and anxiety scale questionnaire was recorded, and fasting blood samples were collected to measure biomarkers, including high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and nitric oxide (NO) at baseline and week 8 following the intervention. RESULTS: The data analysis using ANCOVA showed that supplementation with crocin for 8 weeks significantly lowered hs-CRP levels (p-value= 0.01). In addition, within-group comparisons showed crocin significantly decreased anxiety (p-value= 0.01). However, crocin did not affect serum MDA and NO after 8 weeks of intervention. CONCLUSION: Our findings suggest that crocin may keep promise in attenuating inflammation, evidenced by reducing hs-CRP in patients with MS. However, supplementation for 8 weeks may not be sufficient to improve mental health, and future clinical studies with higher sample sizes and various doses and durations are recommended.

Different factors, such as inflammation, oxidative stress, extracellular matrix degradation and apoptosis, affect the pathophysiology of chronic obstructive pulmonary disease (COPD), as a progressive disease characterised by permanent airflow limitation. Herbal supplements with anti-inflammatory and antioxidant properties can help treat certain chronic diseases. The current study aimed at investigating the preventive effects of crocin supplementation on the serum concentrations of IL-6, TNF-α, exercise capacity and pulmonary function tests (PFT) in patients with COPD. The present prospective randomised clinical trial equally divided fifty-seven patients with COPD into a placebo and an intervention group, who respectively received a placebo and crocin (15 mg twice day for 12 weeks) as a supplement. ELISA was used to measure serum levels of IL-6 and TNF-α, also PFT and exercise capacity based on 6-min walking distance test (6MWD), which was performed at the beginning and end of the study. Crocin improved the results of PFT (P < 0·05) and 6-MWD (P < 0·001) and exerted preventive effects by increasing the serum levels of IL-6 in patients with COPD compared with those in the placebo group (P < 0·05). Intervention with crocin significantly lowered serum levels of TNF-α at the end of the study (P < 0·01). The present findings suggest crocin supplementation improves exercise capacity and PFT in patients with COPD by reducing serum levels of inflammatory factors.

BACKGROUND: Saffron, derived from the stigmas of the Crocus Sativus flower, has been shown in several studies to improve mood and wellbeing in adults experiencing low mood and anxiety. The goals of this study were to examine its mental and physical effects in healthy, recreationally active adults. METHODS: In this 6-week, randomized, double-blind, placebo-controlled study, 62 adults engaging in regular exercise were recruited and randomized to receive a placebo or 28 mg daily of a standardized saffron extract (affron®). Self-report outcome measures include the Physical Activity Enjoyment Scale, Profile of Mood States, and Patient-Reported Outcomes Measurement Information System-29. Participants also wore a wrist-worn heart rate, activity, and sleep monitoring device (WHOOP) to measure changes in sleep quality, resting heart rate, and heart rate variability. To help identify mechanisms of action associated with saffron intake, changes in plasma concentrations of brain-derived neurotrophic factor, oxytocin, and neuropeptide Y were also measured. RESULTS: Based on data collected from all participants, there were no statistically significant between-group differences in changes in any of the outcome measures. However, when changes were analyzed by sex, there were statistically significant greater increases in enjoyment associated with exercise (p =.009) and heart rate variability (p =.001) in male participants taking saffron compared to the placebo. No statistically significant between-group differences were identified in females. CONCLUSIONS: The results of this trial suggest saffron may have beneficial effects in recreationally active males, as evidenced by increased exercise enjoyment and heart rate variability. However, no such benefits were identified in females. Future research using larger sample sizes, varying treatment periods, and additional outcome measures will be required to validate the results from this study and help clarify the mechanisms of action associated with saffron intake.This study was prospectively registered on 30 October 2020 with the Australian and New Zealand Clinical Trials Registry (Trial ID. ACTRN12621000501842). © 2022 The Author(s

OBJECTIVE/BACKGROUND: To validate and extend on previous positive findings of the sleep-enhancing effects of saffron supplementation in adults with unsatisfactory sleep. PATIENTS/METHODS: In this 28-day, 3-arm, parallel-group, double-blind, randomised controlled trial, 120 adults with unsatisfactory sleep received either a placebo, 14 mg, or 28 mg of a standardised saffron extract (affron®), 1 h before bed. Outcome measures included the Pittsburgh Sleep Diary (with sleep quality ratings as the primary outcome measure), Insomnia Symptom Questionnaire (ISQ), Profile of Mood States, Restorative Sleep Questionnaire, the Functional Outcomes of Sleep Questionnaire, and evening salivary melatonin and cortisol concentrations. RESULTS: Compared to the placebo, saffron supplementation was associated with greater improvements in sleep quality ratings (primary outcome measure), mood ratings after awakening, the ISQ total score, and ISQ-insomnia classifications. However, there were no significant differences between the saffron and placebo groups in other questionnaire and sleep diary outcome measures. Sleep improvements were similar for the two administered saffron doses. Compared to the placebo, saffron supplementation was associated with increases in evening melatonin concentrations but did not affect evening cortisol. Saffron supplementation was well-tolerated with no reported significant adverse effects. CONCLUSIONS: These results provide further validation of the sleep-enhancing effects of 28-days of saffron supplementation in adults with unsatisfactory sleep. Further research is required to examine the efficacy and safety of saffron supplementation using objective sleep measures, over a longer duration, in people presenting with a diagnosed insomnia disorder and other psychogenic and demographic characteristics, and into its potential sleep-enhancing mechanisms of action. Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.

The effects of saffron (Crocus sativus L.) on mood disorders have already been established. More recently, its anti-neoplastic effects have provoked a great attention. This study aims to assess the effects of crocin administration during doxorubicin-based chemotherapy of breast cancer on anxiety, depression, and chemotherapy toxicity profile. Seventy-two patients with non-metastatic Her2/neu positive or triple negative breast cancer were enrolled and randomly assigned to receive either 30 mg/day of crocin or placebo during chemotherapy [2:2]. Beck's Depression and Anxiety Inventories were used at baseline and end of the trial. In addition, the ECOG Common Toxicity Criteria were applied to assess chemotherapy side-effects. After the intervention, the degree of anxiety and depression decreased significantly in the crocin group (p = .001 for both) and increased significantly in the placebo-group (p = .006 and p = .036, respectively). There were significantly higher grade II-IV leukopenia (47.2% vs. 19.4%, p = .012) in the crocin group, and grade II-IV hypersensitivity-reaction (30.6% vs. 5.6%, p = .006) in addition to neurological disorders (66.7% vs. 41.7%, p = .03) in the placebo-group. The results indicate that using crocin during chemotherapy in patients with breast cancer has ameliorated anxiety and depression. Moreover, leucopenia increased whereas hypersensitivity reaction and neurological disorders decreased in the crocin group. In addition, a trend toward survival improvement was observed, which is going to be investigated on longer follow up. © 2021 John Wiley & Sons Ltd.

Chronic unpredictable mild stress (CUMS) is an approved method for the induction of depression in rodents. Lithium, as one of the oldest psychiatric drugs, can induce beneficial effects on mood state under stressful conditions. On the other hand, crocin (active component of Saffron) has antioxidant, procognitive, and mood-enhancer effects. In this study, we aimed to investigate the interaction effect of lithium and crocin on mood disturbances and cognitive impairments induced by CUMS. CUMS was performed for 3 weeks. Lithium (100 mg/kg, i.p.), or crocin (30 mg/kg, i.p.), or combination of both was injected during CUMS period (21 injections). Open field test, hot plate, forced swimming test, shuttle box, and Morris water maze were used to evaluate locomotor activity, pain perception, depressive-like behavior, passive avoidance memory, and spatial memory, respectively. The results showed that lithium decreased locomotion and climbing, increased pain threshold and immobility, and impaired passive avoidance and spatial memory in control rats. CUMS also showed all these effects, with more intensity. However, lithium partly reversed the effect of CUMS on locomotion and spatial memory, and completely restored the effect of CUMS on immobility and passive avoidance memory. Also, lithium did not change the effect of CUMS on pain threshold and climbing. Crocin alone, and in combination with lithium significantly reversed all the effects of CUMS. In conclusion, for the first time, the results of the present research showed that the combination of lithium and crocin leads to stronger therapeutic effects on mood disturbances and cognitive impairments induced by chronic stress.

Cytochrome P450 (CYP) enzymes play an important role in the biotransformation of drugs and endogenous substances. Clinical medications and herbal remedies can either enhance or inhibit the activity of CYP enzymes, leading to potential drug interactions between herbal supplements and prescribed medications. Such interactions can lead to serious consequences, especially for drugs with a narrow therapeutic index, such as digoxin, warfarin, and cyclosporine A. In this review article, we provide an updated review of the impact of saffron, and its active constituents, safranal and crocin, on the 12 major human CYP enzymes and possible drug interactions between saffron and prescription drugs. The available evidence indicates that saffron and its active constituents affect the expression or activity of some CYP isoforms, including the CYP1A1/2, CYP3A4, and CYP2E1 subfamily. Considering the important role of these CYPs in the biotransformation of frequently prescribed medications and the activation of procarcinogen into carcinogenic metabolites, it can be expected that the consumption of saffron and its active constituents may influence the pharmacokinetics and toxicity of several substances. In particular, given the critical role of CYP3A4 in drug metabolism, and saffron's inhibitory impact on this CYP enzyme, it appears that saffron's most significant interaction is linked to its inhibition of CYP3A4. In addition, the inhibitory effect of saffron on CYP1A1/2, and CYP2E1 expression can play a role in the chemopreventive effect of this herbal medicine. Additional research is crucial for evaluating the clinical significance of these interactions in patients who consume saffron along with prescription drugs and determining the dose that can lead to drug interactions. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for the treatment of depression. Citalopram is one of the most prescribed SSRIs that is useful for the treatment of depression, obsessive-compulsive disorder, and anxiety disorders. On the other hand, crocin (active constitute of saffron) has pro-cognitive and mood enhancer effects. Also, both citalopram and crocin affect the function and expression of brain-derived neurotrophic factor (BDNF) and synaptophysin, two molecular factors that are involved in cognitive functions and mood. In the present study, we aim to investigate the interaction effect of citalopram and crocin on rats' performance in the open field test (locomotor activity and anxiety-like behavior) and the shuttle box (passive avoidance memory). Citalopram was injected at the doses of 10, 30, and 50 mg/kg, and crocin was injected at the dose of 50 mg/kg; all administrations were intraperitoneal. Real-time PCR was used to assess the expression level of BDNF and synaptophysin in the hippocampus. The results showed that citalopram (30 and 50 mg/kg) impaired passive avoidance memory and decreased BDNF and synaptophysin expression in the hippocampus, while crocin reversed memory impairment, and BDNF and synaptophysin expression in the hippocampus of rats received citalopram 30 mg/kg. Also, crocin partially showed these effects in rats that received citalopram 50 mg/kg. The results of the open field test were unchanged. In conclusion, we suggested that BDNF and synaptophysin may be involved in the effects of both citalopram and crocin. © 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Crocus sativus L., a perennial plant grown mainly around the Mediterranean and Iran, has many medicinal properties including anti-inflammatory, anti-depressive and cancer preventing properties. Aqueous herbal extracts may affect the activity of Phase I and II enzymes involved in xenobiotic metabolism. The present study was designed to determine whether C. sativus infusion alters the activity of CYP1A2, CYP2A6, XO and NAT2 enzymes in humans. Thirty-four healthy volunteers consumed infusion prepared from C. sativus stigmata for six days. Enzyme phenotyping was assessed in saliva and urine using caffeine metabolite ratios as follows: CYP1A2: 17X/137Χ (saliva) and CYP1A2: (AFMU+1U+1X)/17U, CYP2A6: 17U/(17U + 17X), XO: 1U/(1U+1X) and NAT2: AFMU/(AFMU+1U+1X) (urine). Following C. sativus intake, CYP1A2 index was reduced by ∼13.7% in saliva (before: 0.51 ± 0.22, after: 0.44 ± 0.14; p = 0.002) and ∼6.0% in urine (before: 3.81 ± 1.20, after: 3.58 ± 0.92; p = 0.054). CYP1A2 index was significantly reduced only in males (saliva, before: 0.65 ± 0.22, after: 0.51 ± 0.16; p = 0.0001; urine, before: 4.53 ± 1.19, after: 4.03 ± 0.87; p = 0.017) suggesting sexual dimorphism in CYP1A2 inhibition. There was no effect of C. sativus intake on CYP2A6, XO or NAT2 indices. Short-term consumption of C. sativus infusion is unlikely to result in significant herb-drug interactions involving the enzymes studied, with the exception of potential herb-CYP1A2 substrate interaction in males.

Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in the etiology and pathophysiology of FM. They may contribute to a dysregulation of the central pain mechanisms together with the neuroendocrine and immune systems. Pharmacological treatments are the first-line therapy to reduce the symptoms of FM. The US Food and Drug Administration (FDA) indicated gabapentinoid, pregabalin, duloxetine, and milnacipran for adult patients. An alternative approach is widely used, based on therapies including interventions in patient education, behavioral therapy, exercise, pain management, and a healthy diet. A systematic search was performed on PubMed, MEDLINE, EMBASE, and Web of Science databases. The authors established the selection, inclusion, and exclusion criteria. We found a total of 908 articles. This systematic review will include ten articles selected after excluding duplicates and reading the abstracts and full texts. All studies related the effect of drugs to various symptoms caused by fibromyalgia patients with depression, such as insomnia/sleepiness, depression, suicide, difficulty walking/working, pain, fatigue, and nervousness. Although, we concluded that antidepressant drugs are effective in treating depression and pain in fibromyalgia, further studies are needed to understand the etiology of this disease and to find a combination of therapies to increase tolerability and adherence of the patient to the drug, decreasing the adverse effects.

BACKGROUND: Saffron is a traditional herbal medicine that has been used to treat various ailments such as depressive mood. However, the findings of several meta-analyses regarding anti-depressive properties of saffron (Crocus sativus L.) are controversial. The current umbrella meta-analysis was carried out to determine the magnitude and direction of saffron administration on depression. METHODS: Relevant studies were searched in international databases including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central Library up to June 2021. Meta-analysis studies investigating the effects of saffron on depression were considered to include in the study. Random-effects model was used to perform the meta-analysis. Additional analyses including subgroup and sensitivity analyses were carried out. RESULTS: Overall, 7 meta-analyses were included in the study. The results demonstrated that the consumption of saffron resulted in a significant reduction in BDI scores (ES: -3.87; 95% CI: -5.27, -2.46). However, saffron did not change the HAMD scores (ES: -2.10; 95% CI: -5.05, 0.86, p = 0.164) and mixed scores (HAM-D/BDI/DASS) (ES: 0.02; 95% CI: -0.39, 0.43,p = 0.941). CONCLUSION: Present umbrella meta-analysis demonstrated that saffron intake might contribute to alleviation of depression disorder, however, it cannot be considered as a single therapeutic approach to treat depression.

Respiratory Viruses infections (RVI) such as rhinovirus, coronavirus, influenza virus, and adenovirus affect the respiratory and the immune systems. The role of nutrition in the respiratory and immune systems has been studied in some studies, and its importance is undeniable. In addition, one of the key findings in this disease is high inflammation that affects almost all patients. This systematic narrative review aims to answer the question, "Can an anti-inflammatory diet be effective in preventing or treating viral respiratory diseases?" A systematic review search was used for the articles extraction. All studies published in English from 1999 to 2020 investigating dietary inflammatory conditions and RVI were included. Food items with anti-inflammatory properties were selected based on the definition of the dietary inflammatory index (DII). We used Google Scholar, Pub Med, Scopus, Web of Science, Springer, Science Direct, Directory of Open Access Journals, Elsevier, Taylor and Francis, ProQuest, EBSCO, MEDLINE, and SciELO databases for extracting articles. Keywords were restricted by DII. Based on DII, food items/nutrients are involved in inflammation, some of which have anti-inflammatory and some inflammatory properties. Some foods/nutrients, in addition to their anti-inflammatory properties, have antioxidant, antiviral, and immune-enhancing properties. Considering the immune system's involvement, increased inflammation, and involvement of the pulmonary system in RVI and the remarkable role of the anti-inflammatory foods for counteracting them, it is recommended to use a predominantly anti-inflammatory diet along with prevention/control and treatment protocols. An anti-inflammatory diet (based on DII) includes turmeric, ginger, garlic, onions, saffron, dietary vitamin C, vitamin D, zinc, and omega-3 are recommended to reduce infection symptoms and duration.

BACKGROUND: Saffron (stigma of Crocus sativus L.) from Iridaceae family is a well-known traditional herbal medicine that has been used for hundreds of years to treat several diseases such as depressive mood, cancer and cardiovascular disorders. Recently, anti-dementia property of saffron has been indicated. However, the effects of saffron for the management of dementia remain controversial. The aim of the present study is to explore the effectiveness and safety of saffron in treating mild cognitive impairment and dementia. METHODS: An electronic database search of some major English and Chinese databases was conducted until 31st May 2019 to identify relevant randomised clinical trials (RCT). The primary outcome was cognitive function and the secondary outcomes included daily living function, global clinical assessment, quality of life (QoL), psychiatric assessment and safety. Rev-Man 5.3 software was applied to perform the meta-analyses. RESULTS: A total of four RCTs were included in this review. The analysis revealed that saffron significantly improves cognitive function measured by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinical Dementia Rating Scale-Sums of Boxes (CDR-SB), compared to placebo groups. In addition, there was no significant difference between saffron and conventional medicine, as measured by cognitive scales such as ADAS-cog and CDR-SB. Saffron improved daily living function, but the changes were not statistically significant. No serious adverse events were reported in the included studies. CONCLUSIONS: Saffron may have the potential to improve cognitive function and activities of daily living in patients with Alzheimer's disease and mild cognitive impairment (MCI). However, due to limited high-quality studies there is insufficient evidence to make any recommendations for clinical use. Further clinical trials on larger sample sizes are warranted to shed more light on its efficacy and safety.

This paper provides a 10-year update of the 2007 systematic review of herbal medicines studied in a broad range of psychiatric disorders, including depression, anxiety, obsessive-compulsive, seasonal affective, bipolar, psychotic, phobic, somatoform, and attention-deficit hyperactivity disorders. Ovid Medline, PubMed, and the Cochrane Library were searched for herbal medicines with both pharmacological and clinical evidence of psychotropic activity. This updated review now covers clinical trial evidence for 24 herbal medicines in 11 psychiatric disorders. High-quality evidence was found to exist for the use of Piper methysticum (Kava), Passiflora spp. (passionflower) and Galphimia glauca (galphimia) for anxiety disorders; and Hypericum perforatum (St John's wort) and Crocus sativus (saffron) for major depressive disorder. Other encouraging herbal medicines with preliminary evidence include Curcuma longa (turmeric) in depression, Withania somnifera (ashwagandha) in affective disorders, and Ginkgo biloba (ginkgo) as an adjunctive treatment in Schizophrenia. Although depression and anxiety are commonly researched, many other mental disorders still require further prospective investigation. Although the previous review suggested increasing the adjunctive study of select herbal medicines with pharmaceuticals, this was still only found to sparingly occur in research designs. Aside from this, future focus should involve the incorporation of more biomarker analysis, in particular pharmacogenomics, to determine genetic factors moderating response to herbal medicines.

Research in the area of herbal psychopharmacology has increased markedly over the past decades. To date however, a comprehensive review of herbal antidepressant, anxiolytic and hypnotic psychopharmacology and applications in depression, anxiety and insomnia has been absent. A search of MEDLINE (PubMed), CINAHL, PsycINFO, and the Cochrane Library databases was conducted (up to February 21st 2011) on commonly used psychotropic herbal medicines. A review of the literature was conducted to ascertain mechanisms of action of these botanicals, in addition to a systematic review of controlled clinical trials for treatment of mood, anxiety and sleep disorders, which are common comorbid psychiatric disorders. Specific emphasis was given to emerging phytomedicines. Analysis of evidence levels was conducted, as were effect sizes (Cohen's d) where data were available. Results provided evidence of a range of neurochemical, endocrinological, and epigenetic effects for 21 individual phytomedicines, which are detailed in this paper. Sixty six controlled studies were located involving eleven phytomedicines. Several of these provide a high level of evidence, such as Hypericum perforatum for major depression, and Piper methysticum for anxiety disorders. Several human clinical trials provide preliminary positive evidence of antidepressant effects (Echium amoenum, Crocus sativus, and Rhodiola rosea) and anxiolytic activity (Matricaria recutita, Ginkgo biloba, Passiflora incanata, E. amoenum, and Scutellaria lateriflora). Caution should however be taken when interpreting the results as many studies have not been replicated. Several herbal medicines with in vitro and in vivo evidence are currently unexplored in human studies, and along with use of emerging genetic technologies "herbomics", are areas of potential future research.