Saffron (Crocus sativus)

BACKGROUND: The present systematic review and meta-analysis of randomized controlled trials (RCTs) aimed at determining the effect of saffron supplementation on renal function. METHODS: Electronic databases were searched up to February 2021. The risk of bias in individual studies was assessed using the Cochrane Collaboration tool. The overall weighted mean difference (WMD) and their 95% confidence intervals (CIs) were calculated using random-effect models. P < 0.05 was considered statistically significant. RESULTS: A total of 11 trials were included in this study. Saffron had beneficial effect on BUN (WMD = -0.69 mg/dl; 95% CI, -1.36 to -0.01; P=0.046) compared to placebo, with significant heterogeneity (I 2 = 49.6%, P=0.037). However, it had no significant effect on serum Cr (WMD = 0.04 mg/dl; 95% CI: -0.01 to 0.09; P=0.127). CONCLUSION: It seems that saffron supplementation had no significant effect on Cr as a renal function factor. However, BUN reduction was significant in the saffron group compared to placebo.

The worldwide prevalence of obesity is approximately tripled between 1975 and 2016 according to World Health Organization; therefore, obesity is now considered a global pandemic that needs academic and clinical focus. In search of antiobesity agents, Crocus sativus, known widely as saffron, has been praised for its beneficial effects. Several randomized controlled trials (RCTs) have been conducted to investigate the weight lowering effect of saffron. Following PRISMA guidelines, several medical databases were comprehensively searched for RCTs with a population consisting of obese individuals. A random-effects meta-analysis was used to pool estimates across studies, and standardized mean difference (SMD) was used to synthesize quantitative results. Twenty-five RCTs met the inclusion criteria. Meta-analysis showed a nonsignificant decrease for weight (-0.32 kg; CI: -3.15, 2.51; p = 0.82), BMI (-0.06 kg/m2 ;CI:-1.04,0.93; p = .91), waist circumference (-1.23 cm; CI: -4.14, 1.68; p = .41), and hip circumference (-0.38 cm; CI: -5.99, 5.23; p = .89) and a significant decrease of waist-to-hip ratio (SMD = -0.41; CI: -0.73, -0.09; p = .01; I2 = 0%). The mean difference in fasting blood sugar showed a significant reduction in patients with metabolic syndrome (SMD = -0.30; 95% CI: -0.63, 0.03; p = .07; I2 = 0.37%) but a nonsignificant change in the HbA1C level (WMD = 0.05; 95% CI: 0.32, 0.41; p = .79). Despite bearing several limitations, mainly as a result of heterogeneity among included studies, the available evidence indicates saffron supplementation shows promising effects on some cardiometabolic factors among overweight to obese patients; however, further investigations and high-quality evidence are required for more generalizable and comprehensive results. © 2022 John Wiley & Sons Ltd.

CONTEXT: Saffron (Crocus sativus L.) has been proposed as a potential agent to improve renal function in animal studies. But, due to insufficient evidence in human research, further investigation is needed. OBJECTIVE: To fill this knowledge gap, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of saffron supplementation on the measures of renal function indicators in adults. Renal function was assessed based on serum urea, blood urea nitrogen, and creatinine levels. METHOD AND MATERIALS: A systematic search in PubMed/Medline, Scopus, Web of Science, Embase, and Google Scholar databases was done until March 2021 using relevant keywords. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence (95% CI). Nine RCTs were included in the meta-analysis, and their quality was assessed using the Cochrane risk of bias tool. RESULTS: The pooled analysis showed that saffron supplementation had no significant effect on serum urea concentrations (WMD: - 1.05 mg/dl; 95% CI - 5.1 to 3; P = 0.6, I2 = 93%, P < 0.001) and serum creatinine levels (WMD: - 0.006 mg/dl; 95% CI - 0.08 to 0.06; P = 0.8, I2 = 79%, P < 0.001) when compared to the placebo group. In the dose-response analysis, we observed a significant non-linear relationship between the duration of saffron supplementation and serum urea and creatinine levels. CONCLUSIONS: Based on our findings, Saffron supplementation had no significant effect on renal function markers, including urea and creatinine. However, further trials are required to determine the actual effect and safety of saffron intervention in human studies. PROSPERO SUBMISSION ID: 248081. © 2022. The Author(s), under exclusive licence to Springer Nature B.V.

BACKGROUND AND AIMS: Possible protective effects of saffron (Crocus sativus L) have been reported in several randomized clinical trials (RCTs). Current systematic review was performed to summarize the efficacy of saffron intake on liver enzymes. METHODS: An electronic database search was conducted on PubMed/Medline, Scopus, Web of Science, and Cochrane for RCTs comparing effect of saffron and placebo on liver enzymes from inception to July 2021. There was no restriction in language of included studies and we calculated the standardized mean difference (SMD) and 95% Confidence Intervals (CI) for each variable. Random-effect model was used to calculate effect size. RESULTS: Eight studies (n = 463 participants) were included in the systematic review. The saffron intake was associated with a statistically significant decrease in aspartate aminotransferase (AST) (SMD: -0.18; 95% CI: -0.34, -0.02; I2 = 0%) in comparison to placebo intake. Our results also indicated that saffron consumption did not have a significant effect on alanine aminotransferase (ALT) (SMD: -0.14; 95% CI: -0.36, 0.09; I2 = 47.0%) and alkaline phosphatase (ALP) levels (SMD: 0.14; 95% CI: -0.18, 0.46; I2 = 42.9%) compared to placebo. CONCLUSIONS: Saffron intake showed beneficial impacts on circulating AST levels. However, larger well-designed RCTs are still needed to clarify the effect of saffron intake on these and other liver 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: Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder (MDD). Of these, accumulating trials reveal positive effects of the spice saffron (Crocus sativus L.) for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted. OBJECTIVE: The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD. SEARCH STRATEGY: We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies. INCLUSION CRITERIA: The criteria for study selection included the following: (1) adults (aged 18 and older) with symptoms of depression, (2) randomized controlled trial, (3) effects of saffron supplementation on depressive symptoms examined, and (4) study had either a placebo control or antidepressant comparison group. DATA EXTRACTION AND ANALYSIS: Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta-analysis 2 was used to analyze the data. RESULTS: Based on our pre-specified criteria, five randomized controlled trials (n = 2 placebo controlled trials, n = 3 antidepressant controlled trials) were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms (M ES = 1.62, P < 0.001), revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation a

Sleep disturbances are associated with an increased risk of neurodegenerative diseases and alterations in gut microbiota composition. Saffron (Crocus sativus) has been shown to improve sleep and modulate the gut microbiome, but its effect on sleep quality via the gut microbiota-brain axis remains largely unexplored. This randomised, placebo-controlled pilot study investigated the impact of four weeks of saffron supplementation (30 mg day-1) on sleep quality and gut microbiota in older adults (ages 55-85) with self-reported sleep complaints (N = 52). Subjective sleep quality was assessed using validated questionnaires, while objective measures were captured via an electroencephalography-based sleep tracker. Gut microbiota composition was analysed in a subgroup (N = 26). Saffron supplementation significantly improved subjective sleep quality (p = 0.02) and sleep efficiency (p = 0.04). Objective outcomes included reduced latency to persistent sleep (p = 0.003) and shorter sleep onset latency (p = 0.03). Microbiome analysis using linear discriminant analysis effect size (LEfSe) revealed significant increases in Faecalibacterium (q = 0.013), Lachnoclostridium (q = 0.045), Prevotella (q = 0.022), UBA1819 (q = 0.020) and Oscillibacter (q = 0.045), alongside a decrease in Dialister (q = 0.028). Univariate analysis further identified increases in Lachnospiraceae-UGC-001 (p = 0.020) and Roseburia (p = 0.03), with a reduction in Turicibacter (p = 0.045) in the saffron group. Correlational analyses revealed that Oscillibacter and UBA1819 were positively associated with subjective sleep efficiency (r = 0.63, p = 0.0007) and inversely associated with sleep latency (r = -0.39, p = 0.04). Alterations in in Dialister, Turicibacter and UBA1819 correlated with objective sleep quality parameters including wake duration, latency to persistent sleep and wake-after-sleep-onset. In summary, four-weeks saffron supplementation improved both subjective and objective sleep quality in older adults with sleep complaints, and modulated gut microbiota composition, particularly increasing short-chain fatty acids producing bacteria. These findings pave the way for further randomised controlled t

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: Evidence suggests that menopause can be associated with a variety of negative psychological changes such as depression and anxiety, and improving the mental health status of women during menopause is one of the important priorities and challenges of the health system. The aim of this study was to determine the effect of saffron (Crocus sativus L., Iridaceae) herbal tea on happiness in postmenopausal women. METHODS: In this randomized clinical trial which was conducted in 2021, 72 postmenopausal women were enrolled and divided into intervention and control groups. The randomization blocks method was used for random allocation, and the Oxford Happiness Questionnaire was utilized to measure the scores. The intervention included the use of 30 mg of dried stigmas of the saffron plant, which was boiled once (in the morning, in 300 ml of boiling water for 10-15 min) and consumed with white rock candy as one cup of saffron tea daily. To compare the trend of changes and after removing the effect of other variables, generalized estimating equation (GEE) was used. RESULTS: There was no significant difference between the intervention and control groups in any of the quantitative and qualitative characteristics (p > 0.05). The results of paired samples t-test showed that the happiness mean score in the intervention group increased significantly (p < 0.001) from 42.93 ± 8.54 to 61.58 ± 8.24, while in the control group, there was no significant difference between the happiness mean score at the beginning and end of the study (p = 0.861). Also, after applying the treatment program in the intervention group, there was a significant difference between the two groups in terms of the happiness mean scores (p < 0.001). CONCLUSION: Saffron herbal tea had a positive effect on reducing depression and increasing the happiness score; thus, it is recommended that it should be used as a complementary treatment in consultation with the treating physician. TRIAL REGISTRATION: The present study was registered with the code of IRCT20210403050818N1 (Registration date: 09/04/2021) in the Iranian Registry of Clinical Trials. It was also approved by the Ethics Committee of Larestan Uni

In the current study, we aimed to investigate the effect of saffron supplementation on glycemic status, lipid profile, atherogenic indices, and oxidative status in patients with type-2 diabetes (T2DM). In a randomized, double-blind controlled trial, 70 patients were randomly allocated into two groups (n = 35, each) and received 100 mg/day of saffron or placebo for eight weeks. Dietary intake, weight, body mass index (BMI), waist and hip circumferences (WC and HC), waist to hip ratio (WHR), fasting blood sugar (FBS), hemoglobin A1c (HbA1c), insulin, and Homeostatic model assessment for insulin resistance (HOMA-IR), lipid profile, atherogenic indices, oxidative status, and liver enzymes were determined before and after the intervention. At the end of the eighth week, saffron intervention could significantly reduce FBS (7.57%), lipid profile (except high-density lipoprotein cholesterol [HDL-C]), atherogenic indices, and liver enzymes (p < .05). Moreover, saffron could improve oxidative status (nitric oxide [NO] and malondialdehyde [MDA] reduced by 26.29% and 16.35%, respectively). Catalase (CAT) concentration remained unchanged. Saffron supplementation may alleviate T2DM by improving glycemic status, lipid profile, liver enzymes, and oxidative status. Further investigation is necessary to assess possible side effects and confirm the positive effect of saffron as a complementary therapy in clinical recommendations for T2DM. © 2022 John Wiley & Sons Ltd.

OBJECTIVE: We sought to determine the independent and combined effects of saffron and resistance training on markers of inflammation and cardiovascular risk factors in elderly hypertensive patients. METHODS: Hypertensive older men were randomly assigned to a control group (C) or one of three experimental groups [saffron consumption (S), resistance training (R), and resistance training + saffron (RS)] for 12 weeks. Inflammatory markers and lipid profiles were measured at baseline and following the 12-week intervention period. Patients in S and RS received one tablet containing 200 mg of saffron daily. Primary outcomes were analyzed using univariate analysis of covariance (ANCOVA). RESULTS: The RS group had significantly greater reductions in leptin, resistin, MCP-1, and IL-6 as compared with the C, S, and R groups (ps < 0.05). In addition, the RS, S, and R groups had significantly greater reductions in TC and greater increases in HDL-c as compared with the C group (ps < 0.05), but there were no differences between the RS, S, and R groups. Finally, there were no differences between groups for TNF-α, homocysteine, and hs-CRP (ps > 0.05). CONCLUSION: Combining Saffron and resistance training can reduce inflammation and cardiovascular disease risk factors associated with increased risk for hypertension in older men with hypertension.

AIMS: Chronic inflammation is one of the major challenges in the management of obesity and type 2 diabetes mellitus (T2DM). Our primary aim was to assess the anti-inflammatory effects of Saffron (Crocus sativus L.) supplementation and concurrent training in obese men with T2DM. METHODS: Sixty obese men with T2DM (age = 39 ± 5 years; body mass = 93.9 ± 6 kg) were randomly assigned to four groups; concurrent training + placebo (CT; n = 15), saffron supplementation (S; n = 15), concurrent training + saffron supplementation (CTS; n = 15), or control (CON; n = 15). The participants in the CT group performed concurrent training (resistance + aerobic) three times per week for 12 weeks and received daily one pill of placebo (maltodextrin); the participants in the S group supplemented with one pill of 100 mg of saffron daily, and the participants in the CTS group participated in both saffron and training intervention while CON group continued regular lifestyle (no training and no supplementation). Inflammatory markers, body composition (evaluated by a multi-frequency bioelectrical impedance device; Jawon X-Contact 356), and metabolic profile were evaluated before and after interventions. RESULTS: All three interventions significantly (P < .05) decreased TNF-α (CT = -4.22, S = -1.91, CTS = -9.69 pg/mL), hs-CRP (CT = -0.13, S = -0.1, CTS = -0.32 ng/mL), IL-6 (CT = -6.84, S = -6.36, CTS = -13.55 pg/mL), IL-1β (CT = -8.85, S = -6.46, CTS = -19.8 pg/mL), FBG (CT = -6.97, S = -2.45, CTS = -13.86 mg/dL), insulin (CT = -0.13, S = -0.03, CTS = -0.21 mU/L), HOMA-IR (CT = -0.12, S = -0.04, CTS = -0.21), HbA1c (CT = -0.17, S = -0.11, CTS = -0.26%), and increased IL-10 (CT = 1.09, S = 0.53, CTS = 2.27 pg/mL) concentrations. There was a positive correlation between changes in BFP with hs-CRP, IL-6, IL-1β and TNF-α, and IL-10 concentrations across the intervention groups. Additionally, significant differences were observed between the changes for all variables in the CTS group compared to CT, S and CON groups (P < .05). CONCLUSION: It seems that an interaction of saffron supplementation and concurrent training has more efficient effects on anti-inflammatory status compared to saffron s

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.

AIMS: We aimed to determine the independent and combined effects of saffron and resistance training on blood pressure (BP) and some chemical biomarkers in the elderly with hypertension. METHODS: The present study was a randomized clinical trial on hypertensive men aged 60-70 years who were assigned to a control group (CO) and 3 experimental groups; resistance training (RT); saffron (S); and resistance training + saffron (RTS) for 12 weeks. Dynamic resistance training was applied with moderate intensity. Patients in S and RTS received 1 tablet containing 200 mg of saffron daily. BP variables, chemical biomarkers and anthropometric indicators were measured at weeks 0, 6, 12 and 18. Data were analysed by repeated measurements ANOVA with 95% confidence interval (CI). RESULTS: In comparison to the CO (153.3 ± 1.18, CI = 10.9-20.2, P < .001) and S (143.3 ± 1.18, CI = 0.97-10.2, P = .01), RTS (137.7 ± 1.18) reduced systolic BP with the effect size partial η2 of 0.68. Nitric oxide increased in the RTS compared to the CO group (CI = 0.13-0.62, P = .001). There was a significant increase and decrease in adiponectin and endothelin-1 in the S (CI = 0.03-1.20, P = .012; CI = 4.30-17.3, P < .001) and RT (CI = 0.36-1.60, P < .001; CI = 2.26-15.3, P = .003) compared to the CO, respectively. The partial η2 for nitric oxide, adiponectin and ET-1 were 0.35, 0.35 and 0.38, respectively. There was no significant difference between the groups for atrial natriuretic peptide. CONCLUSIONS: Resistance training and consumption of saffron can improve BP in the elderly with hypertension by affecting the factors involved in altering vascular endothelial resistance. The present study was approved by the Ethics Committee of Iran's sports science research institution (IR.SSRC.REC.1398.020) and registered at the Iranian Registry of Clinical Trials (IRCT20190731044398N1). © 2021 British Pharmacological Society.

OBJECTIVES: Saffron (Crocus sativus L.) has been widely used in traditional medicine as a treatment of nervous disorders. Saffron as an antioxidant can be considered effective for treatment of oxidative stress in ischemia stroke. Therefore, the aim of the present study was to investigate the role of aqueous extract of saffron in reducing oxidative stress in ischemic strokes patients. METHODS: Forty patients with acute ischemic stroke were randomly divided into two groups including control group and saffron group. During 4 days of experiment, control group received routine stroke care and saffron group received routine care plus capsule of saffron 400 mg/day (200 mg twice per day). Then, two groups were compared using the National Institute of Health Stoke Scale (NIHSS) and serum oxidative stress biomarkers, at the time of hospital admission and 4 days later as well. RESULTS: On the fourth day after ischemic stroke onset, antioxidant enzymes activities and glutathione (GSH) and total antioxidant capacity (TAC) levels were higher in the saffron group compared to the control group, while malondialdehyde (MDA) level was lower. In addition, the severity of stroke, based on the NIHSS scores, was significantly reduced after 4 days in the saffron group. The severity of stroke was negatively correlated with the levels of GSH and TAC and positively correlated with MDA level. CONCLUSIONS: Saffron has modulatory effects on ischemic-induced oxidative stress due to its free radical scavenging and antioxidant properties. Thus, saffron extract can be considered as a potential candidate therapy of the ischemic brain.

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.

Saffron is harvested from the dried, dark red stigmas of Crocus sativus L. flowers. It is used as a spice for flavoring and coloring food and as a perfume. It is often used for treating several diseases. We assessed the antimutagenic, comutagenic and cytotoxic effects of saffron and its main ingredients using the Ames/Salmonella test system, two well known mutagens (BP, 2AA), the in vitro colony formation assay and four different cultured human normal (CCD-18Lu) and malignant (HeLa, A-204 and HepG2) cells. When only using the TA98 strain in the Ames/Salmonella test system, saffron showed non-mutagenic, as well as non-antimutagenic activity against BP-induced mutagenicity, and demonstrated a dose-dependent co-mutagenic effect on 2-AA-induced mutagenicity. The saffron component responsible for this unusual comutagenic effect was safranal. In the in vitro colony formation test system, saffron displayed a dose-dependent inhibitory effect only against human malignant cells. All isolated carotenoid ingredients of saffron demonstrated cytotoxic activity against in vitro tumor cells. Saffron crocin derivatives possessed a stronger inhibitory effect on tumor cell colony formation. Overall, these results suggest that saffron itself, as well as its carotenoid components might be used as potential cancer chemopreventive agents.

The present study compared the effects of naturally occurring extracts or compound in combination with synthetic selenium compounds on the colony formation and nucleic acid synthesis of cultured human cervical epitheloid carcinoma cells (Hela). Crude extract of bean (Phaseolus vulgaris) or purified lectin from red kidney bean (Phaseolus vulgaris) in combination with selenomethionine were more effective in inhibiting the colony formation of Hela cells than when these cells were treated with these agents alone. Extracts of saffron (Crocus sativus) and selenite have previously been shown to inhibit the colony formation and nucleic acid synthesis by Hela cells in vitro. In the present study we examined the effects of saffron extract in combination with selenite on the colony formation and DNA and RNA synthesis in Hela cells. We found that the treatment of tumor Hela cells with saffron extract in combination with selenite increased the level of inhibition of the colony formation and nucleic acid synthesis in comparison with cells that were treated with only one of these agents. The inhibitory effect of saffron extract in combination with selenite was modified by intracellular sulfhydryl compounds.

AIM: The purpose of this study was to clarify the effects of saffron odor on symptoms unique to women, such as premenstrual syndrome (PMS), dysmenorrhea (menstrual pain) and irregular menstruation. MATERIALS AND METHODS: Thirty-five women with a normal sense of smell were exposed to saffron odor for 20 min. Saliva samples were then collected to measure levels of cortisol (C), testosterone (T) and 17-β estradiol (E) by enzyme immunoassay, and the State-Trait Anxiety Inventory (STAI) was administered as a psychological test. RESULTS: Saffron odor significantly decreased C levels after short-term stimulation (20 min) in both follicular and luteal phases. E level after exposure to saffron odor was increased in both the follicular- and luteal-phase groups. STAI score decreased in the follicular and luteal phases in the saffron group. CONCLUSIONS: The present findings support the existence of physiological and psychological effects of saffron odor in women. Our results indicate that saffron odor exert some effects in the treatment of PMS, dysmenorrhea and irregular menstruation. This is the first report to suggest that saffron odor may be effective in treating menstrual distress.

BACKGROUND: Breast cancer is the most common cancer and the main cause of death because of malignant tumors in women, worldwide. The impact of Crocus sativus on several cancers has been discussed. Recent studies provide evidence regarding the anticancer properties of C. sativus and its bioactive constituents against breast cancer. This study aims to systematically review the efficacy of this botanical drug and its constituents on breast cancer, and their mechanism of action for the first time. Due to the lack of human studies in this field, the present research focused on preclinical studies. METHODS: In this systematic review, scientific databases, including PubMed, Web of Sciences, Google Scholar, Scopus, and Scientific Information Database were explored profoundly. Preclinical studies published until the end of 2024 that had investigated the therapeutic properties of C. sativus, or its bioactive constituents including crocin, crocetin, safranal, or picrocrocin against breast cancer were selected. RESULTS: Forty-four studies examining the effect of C. sativus or its bioactive constituents against breast cancer were obtained. Preclinical in vitro and in vivo studies have demonstrated the potential and targeted anticancer properties of the metabolites found in saffron (C. sativus). These metabolites, such as crocin, crocetin, and safranal, exhibit their anticancer effects through various mechanisms, including induction of apoptosis, modulation of the cell cycle, and other pathways. CONCLUSIONS: C. sativus and its constituents exerts their anticancer activity with different mechanisms. A considerable number of the included studies highlight induction of apoptosis and modulation of the cell cycle. The findings of our study suggest that certain compounds, particularly crocin and crocetin, have significant anticancer properties. In particular, crocin provided the highest level of evidence of efficacy in preclinical research, indicating its potential for further investigation.

The effect of Crocus sativus on several disorders has been discussed or even confirmed, but the efficacy of this herb on the female reproductive system has not been well presented. In this regard, this systematic review comprehensively discussed the efficacy of C. sativus and its main phytochemical compounds on the female reproductive system and its disorders for the first time. In this systematic review, scientific databases, including PubMed, Web of Sciences, Google Scholar, Scopus, and Scientific Information Database, were explored profoundly. In vivo, in vitro, and human studies published until the end of July 2023, which had investigated the pharmacological properties of C. sativus, crocin, crocetin, safranal, or picrocrocin on the female reproductive system, were selected. A total of 50 studies conducted on the effect of C. sativus on the female reproductive system were acquired. These studies confirmed the efficacy of C. sativus or its main phytochemical ingredients in several aspects of the female reproductive system, including regulation of sex hormones, folliculogenesis, ovulation, and protection of the ovary and uterus against several oxidative stress. Several retrieved studies indicated that this herb also can alleviate the symptoms of patients suffering from dysmenorrhea, premenstrual syndrome, menopause, polycystic ovary disease (PCOD), and sexual dysfunction. Furthermore, it is a promising candidate for future studies or even trials regarding ovarian and cervical cancers. This review concluded that C. sativus can improve the symptoms of several female reproductive system disorders, which is particularly due to the presence of phytochemical ingredients, such as crocin, crocetin, and safranal. © 2024 John Wiley & Sons Ltd.

Saffron (Crocus sativus), as an herbal medicine, has been extensively investigated for treating neurological and psychiatric disorders. This systematic review aimed to assess the overall effects of saffron on cognition, depression, anxiety, sleep disorders, attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD). Relevant randomized controlled trials (RCTs) were identified by searching PubMed/Medline, Web of Science, and Clinical Trials databases up to June 2023 according to search terms and inclusion criteria. The participants were either healthy or suffering from some diseases, including neurological and psychiatric disorders, and consumed saffron or its extracts as an intervention. The risk of bias was assessed according to the Cochrane guidelines, and the PRISMA statement was followed. The meta-analysis was performed using RevMan and STATA software. A random-effects or fixed-effects model was used to calculate the pooled effect sizes. Forty-six RCTs were enrolled, and the duration of these trials ranged from 4 to 48 weeks with saffron or its extracts, both alone or in combination with conventional drugs. Saffron was more effective than placebo in improving cognition, depression with an overall effect size of -4.26 (95% CI: -5.76, -2.77), anxiety of -3.75 (95% CI: -5.83, -1.67), and sleep disorders of -1.91 (95% CI: -2.88, -0.93). Saffron was non-inferior to conventional drugs for treating cognitive disorders, depression, anxiety, ADHD, and OCD, and it exhibited good tolerance with few side effects. Saffron may exert protective roles for neurological and psychiatric disorders and represents a relatively favorable and safe treatment. © 2024 John Wiley & Sons, Ltd.

BACKGROUND AND AIMS: Diabetes mellitus is one of the most important life-threatening metabolic diseases of the 21st century. The use of complementary and alternative medicine in diabetic patients seems to be increasing. Saffron, a valuable herbal medicine, has several pharmacological properties such as anti-oxidant effect, which can play important role in ameliorating the complications of diabetes. The aim of this study was to systematically review the therapeutic effects of saffron and its bioactive components on oxidative stress in diabetes mellitus. METHODS: In this systematic review, databases such as PubMed, SCOPUS, Embase, ProQuest, and Web of Sciences were searched from the beginning to December 2021. All eligible in vitro, animal, and human studies that examined the effect of saffron on oxidative stress indices in diabetes were prepared in the form of a full article in English. RESULTS: In the end, only 31of the 389 articles met the criteria for analysis. Of the 31 articles, 4 were in-vitro studies, 25 were animal studies, and 2 were clinical trials studies. Saffron supplementation may activate insulin receptor substrate 1 (IRS1) and peroxisome proliferator-activated receptor gamma (PPAR-γ), which can improve hyperglycemia and insulin transduction signal in adipose tissue, and regulate glucose metabolism, leading to an increased nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1 expression, amelioration of mitochondrial function, and an increased levels of antioxidant enzymes. CONCLUSION: Most studies have shown that saffron supplementation significantly enhanced the production and activity of antioxidant enzymes and decreased oxidative stress indices in diabetes mellitus. However, human pharmacokinetic and more accurate clinical trial studies are needed to determine dose ranges and the exact mechanisms of action of saffron and its active components in diabetes.

BACKGROUND: and amis: Diabetes is one of the major medical problems, which can lead to damage to cells or organs in various parts of the body. Saffron as herbal medicine has contained several active ingredients, including safranal, flavonoids, crocetin, and crocin, which are effective in modulating oxidative stress and inflammation, which can play the main role in reducing the effects of diabetes. However, so far, the effect of saffron on diabetes inflammation has not been evaluated in the form of systematic review studies. The purpose of this systematic study was to evaluate the evidence obtained from in-vitro, animal, and clinical trials studies on the effects of saffron on inflammation in diabetes. METHODS: The present systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements. In this systematic review, databases such as Embase, Pubmed, SCOPUS, ProQuest, and sciences direct database were searched from the beginning to February 2021. All eligible in-vitro, animal and human studies that examined the effect of saffron on inflammatory factors in diabetes were published in the form of a full article in English. RESULTS: In the end, only 20 of the 596 articles met the criteria for analysis. Of the 20 articles, 3 were in-vitro studies, 13 were animal studies, and 4 were human studies. CONCLUSION: The findings of this systematic study (Except for two studies) suggest that saffron supplementation with potential anti-inflammatory properties may reduce the expression of the inflammatory pathway and the production of inflammatory products in diabetes.

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.