This study retrieved Croci Stigma related literature from CNKI, Wanfang, VIP, and Web of Science database, and used bibliometrics and CiteSpace 6.1.R2 software to analyze the published Croci Stigma related articles in Chinese and English from 2000 to 2022. The authors, research institutions, and keywords were visualized and analyzed, and the current status and development trend of Croci Stigma research was summarized by combining the information extraction methods. A total of 1 846 Chinese articles and 2 703 English articles were screened out and included. The results showed a generally steady increase in the number of Croci Stigma related articles. The results of the visualization analysis showed that there were more collaborations between researcher teams and major research institutions in English articles than Chinese articles. The Chinese articles was mainly published by China Pharmaceutical University, and most of the inter-institutional collaborations occurred in neighboring regions. The English articles was mainly published by Iranian institutions, and most of the cooperation occurred within the country, with less transnational cooperation. Keywords analysis showed that the research on Croci Stigma was mainly focused on chemical compositions, pharmacological effects, mechanisms, quality control, etc. It was predicted that the future research hotspots of Croci Stigma would mainly focus on pharmacological mechanism and clinical efficacy. The current research related to Croci Stigma still needs to be developed, cooperation should be strengthened, and more in-depth research should be conducted.
Bibliometrics ; China ; Crocus ; Iran

A hyperuricemic rat model induced by adenine and ethambutol was established to investigate the anti-hyperuricemia activity and its mechanism of the flavonoid extract from saffron floral bio-residues. Sixty-seven SD rats were randomly divided into control group, model group, positive control group, and flavonoid extract groups(with 3 doses), respectively, and each group contained 11 or 12 rats. The hyperuricemic model was established by continuous oral administration of adenine(100 mg·kg~(-1)) and ethambutol(250 mg·kg~(-1)) for 7 days. At the same time, the positive control group was given allopurinol(20 mg·kg~(-1) per day) and the flavonoid extract groups were given the flavonoid extract at doses of 340, 170 and 85 mg·kg~(-1) per day, respectively. On day 8, rat serum, liver, kidney, and intestinal tissues were collected, and the levels of uric acid in serum and tissue, the xanthine oxidase activities and antioxi-dant activities in serum and liver were evaluated, and the kidney histopathology was explored. In addition, an untargeted serum metabolomics study was performed. According to the results, the flavonoid extract effectively reduced the uric acid levels in serum, kidney and ileum and inhibited the xanthine oxidase activities and elevated the antioxidant activities of serum and liver in hyperuricemic rat. At the same time, it reduced the levels of inflammation factors in kidney and protected renal function. Moreover, 68 differential metabolites of hyperuricemic rats were screened and most of which were lipids and amino acids. The flavonoid extract significantly retrieved the levels of differential metabolites in hyperuricemic rats, such as SM(d18:1/20:0), PC[18:0/18:2(92,12Z)], palmitic acid and citrulline, possibly through the following three pathways, i.e., arginine biosynthesis, glycine, serine and threonine metabolism, and histidine metabolism. To sum up, the flavonoid extract of saffron floral bio-residues lowered the uric acid level, increased the antioxidant activity, and alleviated inflammatory symptoms of hyperuricemic rats, which may be related to its inhibition of xanthine oxidase activity and regulation of serum lipids and amino acids metabolism.
Rats ; Animals ; Flavonoids/pharmacology* ; Uric Acid ; Crocus ; Xanthine Oxidase ; Ethambutol/adverse effects* ; Rats, Sprague-Dawley ; Hyperuricemia/drug therapy* ; Kidney ; Antioxidants/pharmacology* ; Plant Extracts/adverse effects* ; Amino Acids ; Adenine/adverse effects* ; Lipids

In order to better utilize saffron floral bio-residues(SFB), a qualitative and quantitative analysis of flavonoids in SFB was conducted using UPLC-MS and UPLC, respectively. On the one hand, 50 flavonols and 5 anthocyanins were putatively characte-rized by using UPLC-Q-TOF-MS. On the other hand, an UPLC method was established for determining the fingerprint of SFB as well as testing the main flavonoids kaempferol-3-O-sophoroside and delphinidin-3,5-di-O-glucoside. Contents of kaempferol-3-O-sophoroside and delphinidin-3,5-di-O-glucoside of 10 batches of samples were 44.21-58.73 mg·g~(-1) and 2.11-6.37 mg·g~(-1), respectively, and the similarities of 10 batches were more than 0.99. In addition, the color of the samples was digitized by using electronic eye technology, and it was found that the color of the samples was significantly correlated with the content of delphinidin-3,5-di-O-glucoside. The richness of flavonoids in SFB indicated its potential for development and utilization, and the large variation in anthocyanin content among samples from different regions suggested that more attention should be paid to the methods of sample pretreatment and storage.
Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Crocus ; Flavonoids ; Flowers ; Tandem Mass Spectrometry

OBJECTIVE: Zearalenone (ZEA) is a mycotoxin with potent estrogenic effects. Saffron is an herbal product that has antioxidant activities. The objective of this study was to investigate the protective role of saffron against reproductive toxicity induced by ZEA in female mice. METHODS: Ninety 8-week-old female mice were randomly allocated into three treatment groups. The first group received an intraperitoneal injection of ZEA (2.5 mg/kg) on alternate days. The second group received ZEA (2.5 mg/kg) on alternate days plus oral saffron daily (50 mg/kg). The third group was treated with a vehicle of 1% dimethyl sulfoxide (DMSO) on alternate days, as a control. Ten mice were euthanized from each group at 30, 60, and 90 days of treatment. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) were assessed. The uterus and ovaries were examined for changes in size or morphology. RESULTS: Serum levels of LH, FSH, E2, and P in the female mice treated with ZEA plus saffron were significantly higher than in those treated with ZEA alone, and were not significantly different from those treated with 1% DMSO. The female mice treated with ZEA alone showed a reduction in size of the uterus and abnormal architecture of the ovaries. CONCLUSION: The administration of saffron to female mice resulted in a significant reduction in ZEA-induced alterations in reproductive hormone levels, the size of the uterus, and the morphology of the ovaries.
Animals ; Antioxidants ; Crocus* ; Dimethyl Sulfoxide ; Estradiol ; Estrogens ; Female* ; Follicle Stimulating Hormone ; Humans ; Injections, Intraperitoneal ; Luteinizing Hormone ; Mice* ; Ovary ; Progesterone ; Uterus ; Zea mays ; Zearalenone

OBJECTIVES: To investigate the effects of saffron aqueous extract (SE) on blood glucose, lipid and pancreatic tissue in streptozocin-induced diabetes mice. METHODS: Diabetes mellitus mice were established by intraperitoneal injection of streptozocin (60 mg/kg) for two consecutive days. The 30 well-established diabetes mice were randomly divided into three groups(=10):diabetic mellitus (DM) group, SE treated (SE) group and positive control (metformin hydrochloride, MH) group. Another ten normal mice were selected as normal control (NC) group. The mice in SE and MH groups were intragastrically administered with SE 100 mg/kg or MH 100 mg/kg once a day for 6 weeks, mice in DM and NC were given normal saline. The amount of food-intake, water consumption and body weight were measured weekly, the changes of the indicators including fasting blood glucose (FBG), oral glucose-tolerance test (OGTT), glycated serum protein (GSP), insulin (INS) and blood lipid were determined after 6 weeks of continuous administration. The pathologic changes in the pancreas tissues were detected by HE staining. RESULTS: Compared with the normal control group, the amount of food-intake, water consumption, area under the curve, FBG, GSP, and total cholesterol (TC) were significantly increased, while fasting weight, INS and high density lipoprotein cholesterol (HDL-c) were dramatically decreased in DM group. Compared with DM group, the water consumption, FBG, area under the curve and TC in SE group were starkly declined with a notable elevation of HDL-c and INS. In addition, the biopsy from DM mice showed the structure of pancreas islet was destroyed and reduced, and vascular proliferation with irregular shape. The damaged pancreas was obviously repaired by giving SE. CONCLUSIONS The saffron aqueous extract had efficacy on blood glucose and blood lipids reduction, improvement on damaged pancreas in streptozocininduced diabetic mice, which suggested that saffron could be used for the treatment in diabetes.
Animals ; Blood Glucose ; Crocus ; chemistry ; Diabetes Mellitus, Experimental ; chemically induced ; drug therapy ; Hypoglycemic Agents ; pharmacology ; Insulin ; blood ; Mice ; Plant Extracts ; pharmacology ; Random Allocation ; Streptozocin

The specific PCR primer was designed base on ITS2 sequence in GenBank, and we developed a SYBRGreen real-time fluorescence quantitative PCR system for identification of Crocus sativus and Carthamus tinctorius source. Compared with Chinese herbal medicine DNA barcode technique, this method showed characteristics of shorter time, higher specificity and sensitivity. Using this method to detect 15 samples, 4 were C. sativus, 8 were C. tinctorius, and the other 3 samples were none of them. The result was in accordance with Chinese herbal medicine DNA barcode. This study lays the foundation for identification of related Chinese medical materials.
Carthamus tinctorius ; Crocus ; Real-Time Polymerase Chain Reaction

High price and poor stability of both crocin-1 and crocin-2 reference substance have become obstacles to HPLC assay of Croci Stigma. A new method based on reference extract was proposed. In this study, the reference extract was prepared from gardenia yellow which is cheap and easy to get The content of crocin-1 and crocin-2 in reference extract was determined and factors affecting stability of reference extract were investigated. Twelve batches of Croci Stigma were analyzed with reference extract and reference substance respectively. The results showed no difference. The presented method is feasible for quality control of Croci Stigma and reference extract is suitable to replace reference substances in assay.
Carotenoids ; analysis ; Chromatography, High Pressure Liquid ; standards ; Crocus ; chemistry ; Drugs, Chinese Herbal ; analysis ; Quality Control ; Reference Standards

BACKGROUNDThroughout the past three decades, increased scientific attention has been given to examining saffron's (Crocus sativus L.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression.

OBJECTIVEThe purpose of this systematic review is to examine and categorize the current state of scientific evidence from randomized controlled trials (RCTs) regarding the efficacy of saffron on psychological/behavioral outcomes.

SEARCH STRATEGYElectronic and non-electronic systematic searches were conducted to identify all relevant human clinical research on saffron. The search strategy was extensive and was designed according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)." Reference lists of articles that met the inclusion criteria were searched. Only English language studies were reviewed.

INCLUSION CRITERIASaffron trials in combination with other substances and saffron safety studies were considered, in accordance with the PRISMA statement. Included studies must have a control group. Included studies must measure a physiological and/or a behavioral outcome.

DATA EXTRACTION AND ANALYSISThe methodological quality of all included studies was independently evaluated by two reviewers using the Jadad score. Mean scores and P-values of measures were compared both inter- and intra-study for each parameter (i.e., depression).

RESULTSTwelve studies met our inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes of: major depressive disorder (n=6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n=4), and weight loss/snacking behaviors (n=1). The data from these studies support the efficacy of saffron as compared to placebo in improving the following conditions: depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition, saffron use was also effective in reducing excessive snacking behavior.

CONCLUSIONFindings from initial clinical trials suggest that saffron may improve the symptoms and the effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings.

Behavior ; drug effects ; Crocus ; Depressive Disorder, Major ; drug therapy ; psychology ; Humans ; Phytotherapy ; methods ; Plant Preparations ; therapeutic use ; Randomized Controlled Trials as Topic

The present study investigated the cytogenetic and testicular damage induced by the antiepileptic drug, sodium valporate (SVP) in albino rats and the effect of saffron aqueous extracts. Treating rats with SVP caused a significant increase in the chromosomal aberrations either structural or numerical and decreased the mitotic index. Besides, animals administered SVP showed DNA damage appeared in the single strand breaks (comet assay). Testis of SVP-treated rats showed many histopathological changes. A significant decrease in seminiferous tubules and their epithelial heights diameters and inhibition of spermatogenesis was recorded. In addition, the number of sperm head abnormalities was increased. Biochemical results revealed an increase in malondialdhyde (MDA) which is lipid peroxidation marker and a significant decrease in the level of serum antioxidant enzyme, catalase (CAT) and reducing antioxidant power (RAP). Animals given SVP and saffron showed an improvement in chromosomal aberrations, mitotic index, DNA damage and testicular alterations caused by SVP. Moreover, MDA decreased and CAT and RAP increased. It is concluded from the present results that the ameliorative effects of saffron extract against SVP-induced cytogenetic and testicular damage in albino rats may be due to the presence of one or more antioxidant components of saffron.
Animals ; Catalase ; Cats ; Chromosome Aberrations ; Comet Assay ; Crocus* ; Cytogenetics* ; DNA Damage ; Lipid Peroxidation ; Mitotic Index ; Rats* ; Seminiferous Tubules ; Sodium* ; Sperm Head ; Spermatogenesis ; Testis

BACKGROUNDDue 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.

OBJECTIVEThe 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 STRATEGYWe 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 CRITERIAThe 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 ANALYSISUsing 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.

RESULTSBased 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 and the antidepressant groups (M ES = -0.15) indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials.

CONCLUSIONFindings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron's efficacy and safety for treating depressive symptoms.

Crocus ; adverse effects ; Depressive Disorder, Major ; drug therapy ; Humans ; Phytotherapy ; Randomized Controlled Trials as Topic