Use of Transcriptome Sequencing to Analyze the Effects of Different Doses of an Astragalus-Rhubarb-Saffron Mixture in Mice with Diabetic Kidney Disease.

Purpose: To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD). Methods: Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis. Results: Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p<0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes. Conclusion: A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.

Characterization of Crocetin Isomers in Serum Samples via UHPLC-DAD-MS/MS and NMR after Saffron Extract (Safr'Inside™) Consumption.

The therapeutic effects of saffron have been reported and described in relation to its major derivatives. Among them, in terms of saffron's properties, crocin and crocetin absorption and bioavailability have been the most studied. Nevertheless, the metabolism of these major compounds of saffron has not yet been entirely elucidated. Current data indicate that the phase 2 metabolism of crocetins go through conjugation reactions. Crocetins could also be present in isomeric forms such as other carotenoids. Nonetheless, there are still shadow areas in regard to the measurements of the different circulating forms of crocetins after oral saffron extract administration (Safr'Inside™). In using various approaches, we propose the identification of a new cis isomeric form of crocetin, the 6-cis-crocetin. This compound was found in human serum samples after an oral administration of saffron extract. The 6-cis-crocetin represents 19% of the total crocetin measured after 45 min of consumption. These data mark, for the first time, the presence of a cis isomeric form of crocetin in human serum samples. Moreover, this study led to the development of an analytical method that is able to identify and quantify both isomeric forms (trans and cis).

Effect of saffron supplementation on the glycemic outcomes in diabetes: a systematic review and meta-analysis.

Aim: This meta-analysis was conducted to investigate the impact of saffron supplementation on the glycemic outcomes in patients with diabetes. Methods: Eight electronic databases were systematically searched from inception to March 31, 2023. RCTs of patients with diabetes receiving saffron compared with placebo which reported glycemic control outcomes were identified. WMD and 95% CIs were pooled using fixed-effects or random-effects models, depending on the significance of heterogeneity. Results: Out of the 837 citations screened, ten RCTs were included in the systematic review and meta-analysis. A total of 562 participants were enrolled, with 292 assigned to the intervention group and 270 to the control group. Saffron was administered at a dose of 5 mg/day to 1 g/day. Compared with placebo, saffron supplementation significantly reduced FPG (WMD = -8.42 mg/dL; 95% CI: -13.37, -3.47; p = 0.001) and HbA1c (WMD = -0.22%; 95% CI: -0.33, -0.10; p < 0.001). However, there was no significant effect on insulin levels, QUICKI and HOMA-IR. Conclusion: Saffron is effective for patients with diabetes in terms of FPG and HbA1c, therefore, it appears to be a promising adjuvant for the glycemic control of DM. However, the overall methodological quality of the identified studies is heterogeneous, limiting the interpretation of the benefit of saffron in diabetes. More long-term follow-up, well-designed and large-scale clinical trials are warranted to draw definitive conclusions. Systematic review registration: The protocol of review was registered in International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42023426353).

Bacillus subtilis stimulates plant growth and production of bioactive components in saffron.

The effects of B. subtilis on the morphology and physiology of saffron were investigated using two types of soils. Three different bacterial suspensions were applied at 14-day intervals to treat saffron. Morphological attributes were recorded, and the amounts of α-crocin and safranal in the stigma extracts were quantified. The longest stigma, petal, and leaf were observed in the treated groups with 105 and 108 cfu/ml. The highest weight of stigma per corm belonged to the treated groups with 102 cfu/ml in unsterile soil and 105 and 108 cfu/ml in sterile soil. Treatment with 102 and 108 cfu/ml caused a significant increase in safranal production in sterile and unsterile peat/perlite. While treatment with 105 and 108 cfu/ml in sterile peat/perlite and exposure to 102 cfu/ml in unsterile peat/perlite soil resulted in an increase in α-crocin. The data showed that B. subtlis triggers the morphological and physiological processes in saffron.

Simple and rapid determination of tartrazine in fake saffron using the metal organic framework (Fe SA MOF@CNF) by HPLC/PDA.

The present study of a novel metal-organic framework containing Fe single atoms doped on electrospun carbon nanofibers (Fe SA-MOF@CNF) based on dispersive micro solid phase extraction (D-µ-SPE) using HPLC-PDA for detection tartrazine in fake saffron samples was designed. The Fe SA-MOF@CNF sorbent was extensively characterized through various techniques including N2 adsorption-desorption isotherms, X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The specific area of surface of the sorbent was 577.384 m2/g. The study variables were optimized via the central composite design (CCD), which included a sorbent mass of 15 mg, a contact time of 6 min, a pH of 7.56, and a tartrazine concentration of 300 ng/ml. Under the optimum condition, the calibration curve of this method was linear in the range of 5-1000 ng/mL, with a correlation coefficient of 0.992. The LOD and LOQ values were ranged 0.38-0.74 and 1.34-2.42 ng/ml, respectively. This approach revealed significant improvements, including high extraction recovery (98.64), recovery rates (98.43-102.72%), and accuracy (RSDs < 0.75 to 3.6%). the enrichment factors were obtained in the range of 80.6-86.4 with preconcentration factor of 22.3. Consequently, the D-µ-SPE method based on synthesized Fe SA-MOF@CNF could be recommended as a sustainable sorbent for detecting tartrazine in saffron samples.

Transcriptome wide identification, characterization and expression analysis of PHD gene family in Crocus sativus.

Crocus sativus L., of the Iridaceae family, yields world's most prized spice, saffron. Saffron is well known for its distinctive aroma, odour and colour, which are imputed to the presence of some specific glycosylated apocarotenoids. Even though the main biosynthetic pathway and most of the enzymes leading to apocarotenoid production have been identified, the regulatory mechanisms that govern the developmental stage and tissue specific production of apocarotenoids in Crocus remain comparatively unravelled. Towards this, we report identification, and characterization of plant homeodomain (PHD) finger transcription factor family in Crocus sativus. We also report cloning and characterisation of CstPHD27 from C. sativus. CstPHD27 recorded highest expression in stigma throughout flower development. CstPHD27 exhibited expression pattern which corresponded to the apocarotenoid accumulation in Crocus stigmas. CstPHD27 is nuclear localized and transcriptionally active in yeast Y187 strain. Over-expression of CstPHD27 in Crocus stigmas enhanced apocarotenoid content by upregulating the biosynthetic pathway genes. This report on PHD finger transcription factor family from C. sativus may offer a basis for elucidating role of this gene family in this traditionally and industrially prized crop. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01410-3.

Effects of Crocus sativus L. Floral Bio-Residues Related to Skin Protection.

The cultivation of Crocus sativus L. to obtain the saffron spice generates a large amount of biowaste, constituted mainly by the flower's tepals. The aim of this work was to evaluate the antioxidant and dermo-protective effect of a complex methanolic extract of C. sativus tepals. The extract's major phenolic content was analyzed using ultra-high performance liquid chromatography with electrospray ionization, coupled with quadrupole-time-of-flight-mass spectrometry (UHPLC-ESI-QTOF-MS). Then, the antioxidant in vitro activity of the extract was studied and related to their chemical composition. Likewise, the effect on intracellular ROS levels in HepG2 and Hs27 cell culture was determined in normal culture and under hydrogen-peroxide-induced oxidative stress. Finally, tyrosinase, hyaluronidase, collagenase, elastase, and xanthine oxidase assays were carried out to determine the dermo-protective capacity of the extract. The high polyphenol content, including flavonoids and anthocyanins, explains the antioxidant effect of the extract both in vitro and in culture assays. The extract has a significant and remarkable protective capacity against oxidative stress induced in culture of the two studied cell lines. It is also remarkable in its ability to inhibit hyaluronidase, tyrosinase, and xanthine oxidase. Results pointed out this biowaste extract as a promising ingredient in the composition of cosmetics.

Reduced Production of Pro-Inflammatory and Pro-Catabolic Factors by Human Serum Metabolites Derived from a Patented Saffron Extract Intake.

Safe and anti-inflammatory plant-based natural products present an increasing focus in the treatment of chronic inflammatory diseases such as osteoarthritis or inflammatory bowel diseases. Among them, saffron, a spice derived from the stigma of Crocus sativus, could have anti-inflammatory properties and would be therefore a promising therapeutic agent for the treatment of such conditions. However, the anti-inflammatory molecular mechanisms of saffron in humans are still understudied and unclear. In this study, combining human serum metabolites and cell cultures, we evaluated the effect of circulating metabolites from the consumption of a patented saffron extract (Safr'InsideTM) on the chondrocytes and colon epithelial cell responses to inflammatory stress. Parametric or non-parametric Analysis of Variance with post hoc tests was performed. We demonstrated that human serum containing metabolites from saffron intake attenuated IL-1ß-stimulated production of PGE2 and MMP-13 in chondrocyte cells and limited the increase in ICAM-1, MCP-1, iNOS, and MMP-3 in human epithelial cells following combined IL-1ß and TNF-α inflammatory stimulation. Altogether, these data provide new findings into the mechanisms underlying the beneficial effects of saffron on chondrocytes and enterocyte cells at the cellular level and in the context of chronic inflammatory disorders.

[Corrigendum] Saffron carotenoids inhibit STAT3 activation and promote apoptotic progression in IL­6­stimulated liver cancer cells.

Following the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 1E on p. 1885, the STAT3 blots shown for the A549 and A2780 cell lines were strikingly similar, such that these data were possibly derived from the same original source where the panels were intended to show the results from differently performed experiments. Upon examining their original data, the authors have realized that an inadvertent error was made in assembling the data in the figure, and the STAT3 data shown correctly for the A549 cell line were erroneously copied across for the A2780 cell line. The corrected version of Fig. 1, showing the correct STAT3 blot for the A2780 cell line in Fig. 1E, is shown on the next page. Note that this error did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. They also apologize to the readership for any inconvenience caused. [Oncology Reports 39: 1883­1891, 2018; DOI: 10.3892/or.2018.6232].

Health risk assessment of heavy metals in saffron (Crocus sativus L.) cultivated in domestic wastewater and lake water irrigated soils.

Irrigation of crops with domestic wastewater (DW) is a common practice in developing countries like India. However, domestic wastewater irrigation poses a risk of migration of toxic heavy metals to edible parts of crops, which requires serious measures to prevent their uptake. In this study, the effect of DW irrigation in comparison with Sarbal Lake water (SLW) and borewell water (BW) on soil characteristics and cultivated saffron (Crocus sativus L.) was investigated. For this purpose, samples of water, soil, and saffron (corm, petal, and stigma) were collected from the suburban area of Pampore, Srinagar district, Jammu and Kashmir, India. The results showed that DW irrigation had the maximum significant (p < 0.05) influence on the physico-chemical and nutrient characteristics of the soil, followed by SLW and BW irrigation, respectively. The growth and yield parameters of saffron were also significantly (p < 0.05) increased in the case of DW irrigation as compared to SLW and BW. The quality ranking of the cultivated saffron was found to be in accordance with the ISO standard (III: BW and II: DW and SLW). On the other hand, DW irrigation showed a significant increase in heavy metal contents (mg/kg) of saffron plant parts such as As (0.21-0.40), Cd (0.04-0.09), Cr (0.16-0.41), Cu (7.31-14. 75), Fe (142.38-303.15), Pb (0.18-0.31), Mn (15.26-22.81), Hg (0.18-0.25), Ni (0.74-1.18), Se (0.13-0.22), and Zn (3.44-4.59), followed by SLW and BW. However, the levels of heavy metals did not exceed the FAO/WHO safe limits. Bioaccumulation factor (BAF), dietary intake modeling (DIM<0.006496), health risk assessment (HRI<0.028571), and target hazard quotient (THQ<1) analyses showed no potential health hazard associated with the consumption of saffron irrigated with DW and SLW. Therefore, the results of this study provide valuable insights into the optimization of irrigation sources for saffron cultivation.

Enhancing the purification of crocin-I from saffron through the combination of multicolumn countercurrent chromatography and green solvents.

Crocin-I, a valuable natural compound found in saffron (Crocus sativus L.), is the most abundant among the various crocin structures. Developing a cost-effective and scalable purification process to produce high-purity crocin-I is of great interest for future investigations into its biological properties and its potential applications in the treatment of neurological disorders. However purifying crocin-I through single-column preparative chromatography (batch) poses a yield-purity trade-off due to structural similarities among crocins, meaning that the choice of the collection window sacrifices either yield in benefit of higher purity or vice versa. This study demonstrates how the continuous countercurrent operating mode resolves this dilemma. Herein, a twin-column MCSGP (multicolumn countercurrent solvent gradient purification) process was employed to purify crocin-I. This study involved an environmentally friendly ethanolic extraction of saffron stigma, followed by an investigation into the stability of the crocin-I within the feed under varying storage conditions to ensure a stable feed composition during the purification. Then, the batch purification process was initially designed, optimized, and subsequently followed by the scale-up to the MCSGP process. To ensure a fair comparison, both processes were evaluated under similar conditions (e.g., similar total column volume). The results showed that, at a purity grade of 99.7%, the MCSGP technique demonstrated significant results, namely + 334% increase in recovery + 307% increase in productivity, and - 92% reduction in solvent consumption. To make the purification process even greener, the only organic solvent employed was ethanol, without the addition of any additive. In conclusion, this study presents the MCSGP as a reliable, simple, and economical technique for purifying crocin-I from saffron extract, demonstrating for the first time that it can be effectively applied as a powerful approach for process intensification in the purification of natural products from complex matrices.

New horizons for the study of saffron (Crocus sativus L.) and its active ingredients in the management of neurological and psychiatric disorders: A systematic review of clinical evidence and mechanisms.

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.

The effect of saffron and its extracts on the treatment of breast cancer: A narrative review.

Breast cancer (BC) is the most prevalent malignancy in women and the second most common disease worldwide, affecting approximately one million individuals annually. Despite the efficacy of conventional chemotherapy, medication resistance and adverse effects limit its effectiveness, leading researchers to explore alternative treatments, including herbal remedies. Saffron, a well-known spice derived from the Crocus sativus L. plant, has shown potential as a BC treatment. The active components of saffron exhibit anti-cancer properties by inducing apoptosis, inhibiting cell division, and modulating signaling pathways implicated in cancer development, such as PI3K/AKT, NF-κB, and MAPK. Clinical findings suggest that saffron can alleviate chemotherapy-induced symptoms, reduce serum tumor marker levels, and enhance quality of life. Preliminary clinical trials are investigating the safety and efficacy of saffron in treating BC, with recent evidence indicating that recommended doses of saffron supplementation are well-tolerated and safe. This review provides an overview of the anti-tumor effects of saffron and its unique chemical composition in BC. However, further research and clinical studies are imperative to fully comprehend the potential of saffron in adjuvant therapy for BC patients.

Therapeutic effects of saffron and its components on neurodegenerative diseases.

Due to an increase in the number of older people in recent years, neurodegenerative diseases as the most important age-related neurological disorders are considered as a great threat to human health. The treatment strategies for these disorders are symptomatic and there is no known definitive treatment; however, recently, several studies have investigated the effectiveness of some herbs and their components in limiting the progression and treatment of neurodegenerative disorders. In this study, we searched Medline (via PubMed), Scopus, Science Direct, and Google Scholar databases. The keywords used in the search were: saffron [title/abstract] or (saffron compound [title/abstract]) and (neurological disorders [title/abstract]), publication date range (2010-2023), and language (English). After applying inclusion and exclusion criteria, 30 articles remained. Of the 30 articles included in the study, six studies on the treatment of neurodegenerative disorders by saffron and its components were in the clinical trial phase, and 24 studies were in the preclinical phase. Saffron and its compounds can play an important role in inhibiting neuroinflammation and excitotoxic pathways, modulating autophagy and apoptosis, attenuating oxidative damage, and activating defensive antioxidant enzymes, resulting in neuroprotection against neurodegenerative diseases. Therefore, this study aimed to review the studies on the effects of saffron and its compounds on the treatment of neurodegenerative diseases.

Saffron (Crocus sativus L.) extract attenuates chronic scopolamine-induced cognitive impairment, amyloid beta, and neurofibrillary tangles accumulation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Crocus sativus L. known as saffron, is a popular food condiment with a high aroma, deep colour, and long and thick threads (stigmas) cultivated in Iran, Morocco, Spain, Italy, China, Japan, France, Turkey, and India. In 'Ayurveda', saffron is acknowledged for its immunostimulant, aphrodisiac, cardiotonic, liver tonic, nervine tonic, carminative, diaphoretic, diuretic, emmenagogue, galactagogue, febrifuge, sedative, relaxant, and anxiolytic activities. The renowned Persian physician and philosopher, Avicenna, delineated saffron as an antidepressant, hypnotic, anti-inflammatory, hepatoprotective, bronchodilator, and aphrodisiac in his book, the Canon of Medicine. Within traditional Iranian Medicine (TIM), saffron is characterized as a mood elevator and a rejuvenator for the body and senses. Further, the ethnopharmacological evidence indicates that saffron has shown an effect against neurodegenerative disorders namely, dementia, Alzheimer's, and Parkinson's with its bioactive constituents i.e., carotenoids and apocarotenoids. AIM: The present study aimed to investigate the potential of standardized (Kashmir Saffron, India) Crocus sativus extract (CSE) in chronic scopolamine-induced cognitive impairment, amyloid beta (Aß) plaque, and neurofibrillary tangles (NFT) accumulation in rat brains by targeting AChE inhibition and scopolamine mechanistic effect. METHODS: The experimental animals were divided into six groups: group 1: normal control, group 2: scopolamine, group 3,4 and 5 rivastigmine tartrate, CSE (p.o. 10 mg/kg, 15 mg/kg, and 20 mg/kg) respectively. Each treatment group received scopolamine after 20 min of dosing, till 4 weeks. The effects of different treatments on learning, acquisition, and reversal memory were performed using a Morris water maze test. In addition to behavioral assessments, biochemical parameters such as AChE, IL-6, and antioxidants were measured in isolated brains. Histological observations were also conducted to assess the presence of Aß plaques and NFT. Furthermore, molecular docking was performed to explore the potential AChE inhibitory activity of the bioactive constituents of standardized CSE. RESULTS: Scopolamine produces memory impairment, and its chronic administration forms Aß plaque and NFT in rat brains. Supplementation with CSE in presence of scopolamine has shown remarkable effects on behavioural activity, special acquisition, and reversal memory. The CSE has also shown promising effects on AChE inhibition and antioxidant activity. The results of the docking study also indicate that trans-crocetin, i.e., a biologically active metabolite of Crocins, has strong AChE inhibitory activity, supported by an in vivo animal experiment. CONCLUSION: Supplementation with CSE significantly attenuates the formation of Aß plaque and NFT in the hippocampus at a dose of 20 mg/kg per day. In addition, CSE also counters scopolamine-induced neuroinflammation.

An overview of pharmacological effects of Crocus sativous and its constituents.

Crocus sativus L. was used for the treatment of a wide range of disorders in traditional medicine. Due to the extensive protective and treatment properties of C. sativus and its constituents in various diseases, the purpose of this review is to collect a summary of its effects, on experimental studies, both in vitro and in vivo. Databases such as PubMed, Science Direct, and Scopus were explored until January 2023 by employing suitable keywords. Several investigations have indicated that the therapeutic properties of C. sativus may be due to its anti-oxidant and anti-inflammatory effects on the nervous, cardiovascular, immune, and respiratory systems. Further research has shown that its petals also have anticonvulsant properties. Pharmacological studies have shown that crocetin and safranal have anti-oxidant properties and through inhibiting the release of free radicals lead to the prevention of disorders such as tumor cell proliferation, atherosclerosis, hepatotoxicity, bladder toxicity, and ethanol induced hippocampal disorders. Numerous studies have been performed on the effect of C. sativus and its constituents in laboratory animal models under in vitro and in vivo conditions on various disorders. This is necessary but not enough and more clinical trials are needed to investigate unknown aspects of the therapeutic properties of C. sativus and its main constituents in different disorders.

Effect of vitamin E with and without saffron on the sexual function in women of reproductive age with sexual dysfunction: a randomized controlled trial.

BACKGROUND: Sexual satisfaction is a crucial part of a fulfilled life, and the ability to have satisfying sexual function is crucial to one's sexual health. This study investigated the effect of the combined administration of saffron and vitamin E and vitamin E alone on the sexual function of women in their reproductive years. METHODS: A triple-blind randomized controlled trial was conducted with 50 participants experiencing sexual dysfunction without comorbid sleep disorders or severe depression. They were allocated into two groups using a block randomization method (stratified based on the severity of moderate or mild/normal depression). During the 8-week intervention period, participants in the experimental group were administered a 15 mg saffron capsule (safrotin) in the morning and a combination capsule containing 15 mg saffron and 50 mg vitamin E (safradide) in the evening. During the same period, the control group consumed one saffron placebo capsule in the morning and one capsule containing 50 mg of vitamin E and saffron placebo in the evening (in identical appearance to safradide). The Female Sexual Function Index was used to assess sexual function, and the Depression, Anxiety, and Stress Scale-21 (DASS-21) was used to measure levels of depression, anxiety, and stress. These measures were administered at baseline as well as four and eight weeks post-intervention, with an additional measurement taken four weeks after the intervention ceased. The repeated measures ANOVA, ANCOVA, and Mann-Whitney U tests were used to compare the groups. RESULTS: Following the intervention, the experimental group (saffron and vitamin E) demonstrated a statistically significant increase in the overall mean score of sexual function compared to the control group (placebo of saffron and vitamin E) (adjusted mean difference (AMD): 4.6; 95%CI: 3.1 to 6.1; p < 0.001). The mean scores for sexual function dimensions, namely libido, arousal, orgasm, and satisfaction, except for pain, were consistently higher than those of the control group across all time points (p < 0.001). Additionally, the mean score for lubrication was significantly higher only at the eighth-week measurement (p = 0.004). The mean depression score in the experimental group was significantly lower than in the control group at all-time points, i.e., four (p = 0.011) and eight weeks after the intervention (p = 0.005), and four weeks after the end of the intervention (p = 0.007). The experimental group exhibited a statistically significant decrease in mean anxiety score compared to the control group at four weeks into the intervention (p = 0.016) and four weeks following the end of the intervention (p = 0.002). At eight weeks post-intervention, however, there was no significant difference between the groups (p = 0.177). Additionally, the experimental group exhibited a significant reduction in the overall mean stress score compared to the control group after the intervention (AMD: -2.3; 95%CI: -3.1 to -1.5; p < 0.001). CONCLUSION: Using the combination of saffron and vitamin E is more effective in improving sexual function and its domains compared to vitamin E alone in women of reproductive age with sexual dysfunction without severe depression. Also, it diminishes the degree of depression, anxiety, and stress more compared to vitamin E alone. However, further research is required to arrive at a more definitive conclusion. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT): IRCT20100414003706N36. Date of registration: 17/05/2020; URL: https://en.irct.ir/trial/45992 ; Date of first registration: 21/05/2020.

NAMPT­NAD+ is involved in the senescence­delaying effects of saffron in aging mice.

As the proportion of the elderly population grows rapidly, the senescence-delaying effects of Traditional Chinese Medicine is being investigated. The aim of the present study was to investigate the senescence-delaying effects of saffron in naturally aging mice. The active ingredients in an aqueous saffron extract were determined using high-performance liquid chromatography (HPLC). Mice were divided into saffron (8- and 16-months-old) and control groups (3-, 8-, and 16-months-old), and saffron extract was administered to the former groups for 8 weeks. The open field test and Barnes maze test were used to evaluate the locomotor activity, learning and memory function of the mice. The levels of inflammatory factors in the brain were determined by ELISA. In addition, the activities of acetylcholinesterase (AChE) and superoxide dismutase, and the contents of malondialdehyde and nicotinamide adenine dinucleotide (NAD+) were detected by enzyme immunoassay, and the content of NAMPT was detected by ELISA, western blotting and reverse transcription-quantitative PCR. The cellular distribution of NAMPT and synaptic density were evaluated by immunofluorescence, and the pathological morphologies of the liver, skin, kidneys were observed by hematoxylin and eosin staining. HPLC revealed that the crocin and picrocrocin contents of the saffron extract were 19.56±0.14 and 12.00±0.13%, respectively. Saffron exhibited the potential to improve the learning and memory function in aging mice as it increased synaptic density and decreased AChE activity. Also, saffron ameliorated the pathological changes associated with organ aging, manifested by increasing the number of hepatocytes and the thickness of the skin, and preventing the aging-induced ballooning and bleeding in the kidneys. Furthermore, saffron increased the contents of NAMPT and NAD+ in the brain and decreased the content of NAMPT in the serum. In addition, it changed the cellular distribution of NAMPT in aging mice, manifested as reduced NAMPT expression in microglia and astrocytes, and increased NAMPT expression in neurons. Saffron also decreased the contents of proinflammatory cytokines and oxidative stress factors in aging mice. Altogether, these findings indicate that saffron exerts senescence-delaying effects in naturally aging mice, which may be associated with the NAMPT-NAD+ pathway.

Optimization of Bioactive Compound Extraction from Saffron Petals Using Ultrasound-Assisted Acidified Ethanol Solvent: Adding Value to Food Waste.

The saffron industry produces large by-products, including petals with potential bioactive compounds, which are cheap and abundant, making them an attractive alternative to expensive stigmas for extracting bioactive components. This study aimed to optimize the extraction conditions of bioactive compounds from vacuum-dried saffron petals using an ultrasound-assisted acidified ethanol solvent. Three factors were considered: ethanol concentration (0-96%), citric acid concentration in the final solvent (0-1%), and ultrasound power (0-400 watt). This study examined the effects of these factors on parameters like maximum antioxidant activity, total anthocyanin content, total phenolic content, and the total flavonoid content of the extraction. This study found that saffron petal extract's antioxidant activity increases with higher ethanol concentration, citric acid dose, and ultrasound power, but that an increased water content leads to non-antioxidant compounds. Increasing the dosage of citric acid improved the extraction of cyanidin-3-glucoside at different ultrasound power levels. The highest extraction was achieved with 400 watts of ultrasound power and 1% citric acid. Ethanol concentration did not affect anthocyanin extraction. Higher ethanol concentration and greater citric acid concentration doses resulted in the maximum extraction of total phenolic content, with a noticeable drop in extraction at higher purity levels. This study found that increasing the proportion of citric acid in the final solvent did not affect flavonoid extraction at high ethanol concentration levels, and the highest efficiency was observed at 200 watts of ultrasound power. The optimum values of the independent parameters for extracting bioactive compounds from saffron petals included 96% ethanol concentration, 0.67% citric acid concentration, and 216 watts of ultrasound power, resulting in a desirability value of 0.82. This ultrasound-assisted acidified ethanolic extract can be used in the food industry as a natural antioxidant and pigment source.

Valorization of saffron (Crocus sativus L.) stigma as a potential natural antioxidant for soybean (Glycine max L.) oil stabilization.

Synthetic antioxidants are known for their efficiency to improve vegetable oil oxidative stability. But owing to their harmful effects on human health, edible oil industry is seeking for safe and healthy natural antioxidants. The present work was setup with the aim of improving soybean oil (SO) oxidative stability by using saffron (Crocus sativus L.) stigmas collected in Morocco. Saffron stigmas were used as a natural antioxidant at various concentrations (0.2, 0.3, and 0.6%) in soybean oil compared to tocobiol (0.3%) as a synthetic antioxidant (the positive control). Performances of such natural and synthetic antioxidants were evaluated by measuring oil basic quality indices under accelerated storage at 60 °C for 12 weeks. Such indices consisted of free fatty acids (FFA), peroxide value (PV), anisidine value (p-AV), total oxidation value (TOTOX), UV extinction coefficients (K232 and K270), fatty acids composition (FA), and iodine value (IV). The obtained data show that there were significant (p < 0.05) increases in FFA, PV, p-AV, K232, K270, and TOTOX but no much variations were observed for FA and IV especially in saffron stigmas fortified oils across storage times. However, in the case of oils fortified with saffron stigmas at different doses, such an increase was of a lesser magnitude (for FFA, PV, p-AV, K270, and TOTOX) as compared to tocobiol. These outcomes were confirmed by principal component analysis with strong positive correlations (p < 0.001) among FFA, PV, p-AV, K232, K270, and TOTOX. The most important, for which determination coefficient R2 > 0.9, were modeled through simple regressions. In conclusion, saffron stigmas with the different doses performed better than the positive control (tocobiol) regardless of the storage time. It could be concluded that saffron stigmas are a promising natural antioxidant, alternative to synthetic antioxidants, to enhance the oxidative stability of edible oils.