crocin and safranal

Saffron (

Topics: Antioxidants; Carotenoids; Crocus; Cyclohexenes; Oxidative Stress; Plant Extracts; Terpenes; Vitamin A

Schizophrenia is a chronic mental devastating disease. Current therapy suffers from various limitations including low efficacy and serious side effects. Thus, there is an urgent necessity to develop new antipsychotics with higher efficacy and safety. The dried stigma of the plant

Topics: Animals; Antipsychotic Agents; Carotenoids; Crocus; Cyclohexenes; Humans; Medicine, Traditional; Molecular Structure; Plant Extracts; Schizophrenia; Terpenes

Saffron and its main components have traditionally been used as pharmaceutical agents. Current experimental research projects have also exhibited their applications in a wide spectrum of disorder treatments.. This review covers the demonstrated findings and patents on therapeutic/pharmaceutical properties of saffron and related derivatives, since 2000 to bold their outstanding merit on human health. An extensive literature review was performed in USP Patent, Patentscope, Espacenet and Google Patent in the field of CNS, cardiovascular, urogenital, dermatological and inflammatory disorders.. The growing body of patents showed the value of saffron and the respective crucial components alone or in combination with the other raw materials, herbal extracts, to apply in various therapeutic/pharmaceutical areas. They could be engaged as an adjuvant treatment in phototherapy, cancer, cardiovascular and neurodegenerative diseases and hypoxia-induced dangerous conditions. However, the application of these components in the clinic has been limited to very few drugs yet. This might be due poor clinical trials data. According the human trend toward the use of plant-derived compounds instead of medicines derived from chemical substances, special attention must be focused to link the worth of saffron, herbal medicine of third millennium, from basic sciences to patients' bed.

Topics: Animals; Carotenoids; Crocus; Cyclohexenes; Drug Design; Humans; Patents as Topic; Plant Extracts; Terpenes; Vitamin A

Crocus sativus is an herbaceous plant that belongs to family Iridaceae. It is commonly known as saffron and has been used for medicinal purposes since many centuries in India and other parts of the world. Saffron of commercial importance comprises of dried stigmas of the plant and is rich in flavonoids, vitamins, and carotenoids. Carotenoids represent the main components of saffron and their cleavage results in the formation of apocarotenoids such as crocin, picrocrocin, and safranal. Studies conducted during the past two decades have revealed the immense therapeutic potential of saffron. Most of the therapeutic properties are due to the presence of unique apocarotenoids having strong free radical scavenging activity. The mode of action of these apocarotenoids could be: modulatory effects on detoxifying enzymes involved in combating oxidative stress, decreasing telomerase activity, increased the proapoptotic effect, inhibition of DNA, RNA and protein synthesis, and by a strong binding capacity of crocetin with tRNA. The present review focuses on the therapeutic role of saffron and its bio oxidative cleavage products and also highlights the possible molecular mechanism of action. The findings reported in this review describes the wide range of applications of saffron and attributes its free radical scavenging nature the main property which makes this spice a potent chemotherapeutic agent for the treatment of various diseases.

Topics: Animals; Antineoplastic Agents; Carotenoids; Crocus; Cyclohexenes; Flavonoids; Glucosides; Humans; Plant Extracts; Terpenes

Saffron, the dried stigmas of Crocus sativus L., is a highly valued agricultural product that is used mainly as a food coloring and flavoring agent. Three main secondary metabolites of Crocus sativus including crocin, picrocrocin, and safranal are responsible for the color, the bitter taste and for the odor and aroma, respectively. As a component of traditional medicine, saffron has been utilized as a medicinal herb for treating various ailments including cramps, asthma, liver disease, menstruation disorders, pain, and in the pathogenesis of cancer.. To summarize the recent published data on the chemo-preventive properties of Crocus sativus in cancer treatment.. We conducted a non-systematic review of the literature.. A search of English-language literature was performed using Scopus, EMBASE and PubMed. We applied no restriction in time. Articles were searched using the keywords "Lung", "breast", "skin", "prostate", "leukemia", "cancer", "neoplasm", "tumor", "malignancy", "saffron", "crocus sativus", "crocin", "crocetin", "picrocrocin", and "safranal".. Saffron has been reported to exert anti-tumor and anti-cancer effects in various types of cancer including lung cancer, breast cancer, leukemia, skin cancer and prostate cancer. This appears to be via various mechanisms including: the induction of apoptosis, arresting cell cycle progression, suppressing expression of matrix metalloproteinase, modulatory effects on some phase II detoxifying enzymes and decreasing expression of inflammatory molecules are potential mechanisms of saffron-induced anticancer effects.. Saffron possesses potent anti-tumor properties and represents an efficacious and safe treatment.

Topics: Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Carotenoids; Cell Cycle; Crocus; Cyclohexenes; Female; Food Coloring Agents; Glucosides; Humans; Male; Secondary Metabolism; Terpenes; Vitamin A

Crocus sativus L. (Saffron) has long been known for multiple target therapeutic uses. The plant metabolism is well investigated and the main metabolites related to saffron organoleptic qualities are crocin, crocetin, picrocrocin, and safranal. Particularly, the most abundant of them, such as crocin and safranal, are investigated for their multiple biological activities and known as potential drugs. We aimed to review the constituent features of the plant, along with its potential therapeutic effects in depression, neurodegenerative diseases, diabetes mellitus, atherosclerosis, cancer, and sexual dysfunction. A systematic literature search was conducted in PubMed, Medline, Scopus, and EMBASE, with particular attention to preclinical and clinical studies. Although saffron and its components showed potential clinical applications, further investigations are necessary to confirm the effective use of "Red Gold" and its real applications in clinical practice.

Topics: Alzheimer Disease; Animals; Atherosclerosis; Carotenoids; Crocus; Cyclohexenes; Depression; Glucosides; Humans; Neoplasms; Phytotherapy; Plant Extracts; Sexual Dysfunction, Physiological; Terpenes; Vitamin A

Cancer is a disorder which has noted a significant rise in incidence worldwide and continues to be the largest cause of mortality. It has a dramatic impact on human life expectancy and quality of life in spite of the increase in technology and the treatments available for cancer patients. These new therapeutic options being chemotherapy, radiotherapy, photolytic therapy and catalytic therapy are known to have many adverse reactions and also no better positive outcomes than before. Hence, research is now focused more on utilizing the vast repertoire of traditional medicinal knowledge i.e. the use of flora for treatment of cancer rather than the use of chemicals. One such herb is the Crocus sativus L., commonly known as Saffron, rich in carotenoids - crocin, crocetin and safranal. Various studies have been carried out over the past few years to confirm the anti-cancer properties of saffron, both in vivo using animal models and in vitro using human malignant cell lines on various types of cancers with positive results. The proposed mechanism of actions has also been worked upon. This review is aimed to provide a brief overview on the anti-tumor potential of saffron focusing on the molecular mechanism involved.

Topics: Animals; Antineoplastic Agents; Carotenoids; Crocus; Cyclohexenes; Humans; Terpenes; Vitamin A

The spice saffron is made from the dried stigmas of the plant

Topics: Antidepressive Agents; Antineoplastic Agents; Antioxidants; Carotenoids; Color; Crocus; Cyclohexenes; Functional Food; Glucosides; Humans; Phytochemicals; Plants, Medicinal; Spices; Terpenes; Vitamin A

Saffron (Crocus sativus L.) has a long history of use as a food additive and a traditional medicine for treating a number of disorders. Prominent bioactives of saffron are crocin, crocetin and safranal.. The aim of this study was to carry out an extensive patent search to collect information on saffron bioactives and their derivatives as therapeutic and cosmeceutical agents. All patents related to the area of interest published globally till date have been reviewed. Moreover, a recent synthetic biology approach to cost effective and consistent production of saffron bioactives has been highlighted.. A patent search strategy was designed based on keywords and concepts related to Crocus sativus L. and its bioactives- safranal, crocin and crocetin in combination with different patent classification codes relevant to the technology areas. This search strategy was employed to retrieve patents from various patent databases. The patents which focused on therapeutic or cosmetic applications and claimed compositions comprising crocin, crocetin or safranal as the main active component were selected and analysed.. Maximum patenting activity was noticed towards the use of these bioactives in the treatment of neurological disorders followed by multiple uses of the same compound, use in treatment of metabolic disorders and use as cosmeceuticals. Interestingly, there were no patent records related to use of these bioactives in treating infectious disorders.. Our patent analysis points out the populous and less explored uses of saffron bioactives and areas where there is further scope for research and growth. Recently developed synthetic biology approach is contributory in improving availability, consistency and cost effectiveness of saffron bioactives.

Topics: Animals; Biological Factors; Carotenoids; Cosmeceuticals; Crocus; Cyclohexenes; Databases, Factual; Humans; Metabolic Diseases; Nervous System Diseases; Patents as Topic; Plant Extracts; Synthetic Biology; Terpenes; Vitamin A

Saffron (Crocus savitus) is a Middle-Eastern herb with strong antioxidant properties. Its major constituents, safranal, crocin, and crocetin, are also antioxidants and bear structural similarities to other well-known natural antixodant substances, such as zeaxanthin. Given the role of oxidative stress in many diseases, considerable interest has been shown into the potential role of saffron supplementation as a treatment for a range of diseases. In vitro and animal studies have provided evidence that saffron and its constituents may be potent therapies for a range of pathologies, including Alzheimer's disease, age-related macular degeneration (AMD) and cardiac ischemia. Whether these findings translate into clinical efficacy, however, has as of yet been incompletely assessed. This makes assessing the role of saffron supplementation in these diseases difficult. Here, we review the current human clinical evidence supporting saffron supplementation as a treatment for a range of pathologies and the underlying science supporting its use.

Topics: Affect; Animals; Antioxidants; Cardiovascular System; Carotenoids; Clinical Trials as Topic; Cognition; Crocus; Cyclohexenes; Disease Models, Animal; Humans; Oxidative Stress; Phytotherapy; Plant Preparations; Reproduction; Terpenes; Vision, Ocular; Vitamin A; Zeaxanthins

In this review, we introduce the traditional uses of saffron and its pharmacological activities as described by either Avicenna in Book II, Canon of Medicine (al-Qanun fi al-tib) or from recent scientific studies. Modern pharmacological findings on saffron are compared with those mentioned in Avicenna's monograph. A computerized search of published articles was performed using MEDLINE, Scopus and Web of Science databases as well as local references. The search terms used were saffron, Crocus sativus, crocin, crocetin, safranal, picrocrocin, Avicenna and 'Ibn Sina'. Avicenna described various uses of saffron, including its use as an antidepressant, hypnotic, anti-inflammatory, hepatoprotective, bronchodilatory, aphrodisiac, inducer of labour, emmenagogue and others. Most of these effects have been studied in modern pharmacology and are well documented. The pharmacological data on saffron and its constituents, including crocin, crocetin and safranal, are similar to those found in Avicenna's monograph. This review indicates that the evaluation of plants based on ethnobotanical information and ancient books may be a valuable approach to finding new biological activities and compounds.

Topics: Carotenoids; Cosmetics; Crocus; Cyclohexenes; Herbal Medicine; History, Medieval; Incunabula as Topic; Plant Extracts; Terpenes; Vitamin A

In recent years phytotherapy has been explored as a source for alternative treatments for mood disorders. One potential candidate is saffron (Crocus sativus L.), whose main bioactive components are crocins and safranal.. The aim of this study was to investigate the efficacy of affron. Analysis indicated a significant decrease in negative mood and symptoms related to stress and anxiety at a 28mg/day dose (with a significant difference between 28mg/day and placebo on the POMS Total Mood Disturbance scale, p<0.001, d=-1.10), but no treatment effect at the 22mg/day dose.. The main weaknesses of this investigation were found in the self-reporting nature of both the screening and the testing.. affron

Topics: Adolescent; Adult; Affect; Aged; Anxiety; Carotenoids; Crocus; Cyclohexenes; Depression; Depressive Disorder; Double-Blind Method; Female; Flowers; Humans; Male; Middle Aged; Phytotherapy; Plant Extracts; Self Report; Stress, Psychological; Terpenes; Young Adult

In this work, a four-factor five-level full factorial central composite design (CCD) was used to optimize the ultrasound-assisted extraction (UAE) of saffron major components, namely picrocrocin, safranal and crocin. The process parameters included ethanol concentration (0-100%), extraction time (2-10 min), duty cycle (0.2-1.0) and ultrasonic amplitude (20-100%). The extracted compounds were measured both by spectrophotometry and chromatography techniques. The results revealed that the middle concentrations of ethanol and relatively long process durations along with high duty cycles and ultrasonic amplitudes had the most profound impact on the yields of the extracted bioactives. UAE was optimized using response surface methodology (RSM) and artificial bee colony (ABC); a comparison between these methods indicated their optimization power was approximately the same. According to the RSM analysis, an ethanol concentration of 58.58%, extraction time of 6.85 min, duty cycle of 0.82 and amplitude of 91.11% were the optimum extraction conditions, while the optimal conditions resulting from ABC were 53.07%, 7.32 min, 0.93 and 100% for the UAE variables respectively. Finally, HPLC analysis was carried out on the UAE optimum extract resulting from RSM. Four crocetin esters were detected in the optimal extract.

Topics: Carotenoids; Coloring Agents; Crocus; Cyclohexenes; Ethanol; Glucosides; Plant Extracts; Terpenes

Saffron (Crocus sativus L.) has been introduced as a potential promising natural antioxidant with anti-obesity properties. In Persian Medicine, saffron has been used to control appetite and obesity.. The present study aims to investigate the effect of saffron and its bioactive compounds on adipocyte differentiation in human adipose-derived stem cells (ADSCs).. Flow-Cytometric analysis was performed to quantify the cell surface markers. The extracts cytotoxicity on hASCs was measured using alamarBlue® assay whereas their activities against adipocyte differentiation were studied using Oil Red O staining. The level of Peroxisome proliferator-activated receptor-γ (PPARγ), Fatty Acid Synthetase (FAS), and Glyceraldehyde-3-phosphate dehydrogenase (GAPHD) which are key proteins in cell differentiation was investigated by western blot analysis.. Flow-cytometry revealed the mesenchymal stem cells markers, CD44 and CD90, on ADSCs surface. The saffron, crocin, and crocetin significantly inhibited adipocyte differentiation while saffron up to 20 μg/mL and crocin, crocetin and safranal up to 20 μM did not exhibit cytotoxicity. The western blotting analysis revealed a remarkable reduction in the level of PPARγ, GAPDH, and FAS proteins by 10 and 20 μM of crocin and 2.5 and 5 μM of crocetin.. It seems that saffron, crocin, and crocetin could efficiently inhibit the differentiation of hASCs with benefits for the treatment and prevention of obesity.

Topics: Adipocytes; Carotenoids; Cell Differentiation; Crocus; Cyclohexenes; Humans; Mesenchymal Stem Cells; Obesity; Plant Extracts; PPAR gamma; Terpenes; Vitamin A

The dehydration process is a prerequisite to preserve saffron for a long time. According to this process, saffron shows differences in the main compounds responsible for its quality (colour, taste, aroma, and flavonol content). At present, the freeze-drying method obtains dried products with the highest quality. Viruses can modify the physiology and metabolism of plants, being able to affect the activities of several enzymes. For this reason, the main compounds of saffron have been analyzed under two different dehydrating processes, freeze-drying and dark-drying, considering their infection status with the Saffron latent virus (SaLV). Results showed that the picrocrocin and safranal content enables to differ dark-dried samples from freeze-dried ones. Besides, the kaempferol-3-O-sophoroside-7-O-glucoside content allows differentiating between SaLV-infected (SaLV

Topics: Carotenoids; Crocus; Cyclohexenes; Desiccation; Glucosides; Iran; Kaempferols; Phytochemicals; Plant Diseases; Prevalence; Terpenes; Virus Diseases

Saffron stigmas are widely used as food additives and as traditional medicine in Iran and many other countries. The unique taste, flavor and pharmaceutical properties of saffron stigmas are due to the presence of three apocarotenoids secondary metabolites crocin, picrocrocin and safranal. There is limited knowledge about the effect of environmental stresses on the metabolism of apocarotenoids in saffron. We analyzed the content of crocin and picrocrocin and the expression of key genes of apocarotenoid biosynthesis pathways (CsCCD2, CsCCD4, CsUGT2, CsCHY-β and CsLCYB) in saffron plants exposed to moderate (90 mM) and high (150 mM) salt (NaCl) concentrations. Measuring ion concentrations in leaves showed an increased accumulation of Na

Topics: Biosynthetic Pathways; Carotenoids; Chromatography, High Pressure Liquid; Crocus; Cyclohexenes; Gene Expression Regulation, Plant; Glucosides; Plant Leaves; Potassium; Real-Time Polymerase Chain Reaction; Salt Stress; Sodium; Sodium Chloride; Terpenes

Plant acoustic frequency technology (PAFT) is the effect or treatment of a plant with a specific frequency sound wave.. The sound waves with different frequencies and a sound pressure level 77 dB were emitted on the saffron corms in a controlled environment using aeroponic cultivation and the contents of crocin, picrocrocin and safranal in their produced stigmas were analysed by high-performance liquid chromatography. For this purpose, the corms were divided into two groups. In group 1, sound waves with the frequencies of 0.5, 1 and 2 kHz were emitted on saffron corms in different stages of sprouting, flowering and the whole stage of sprouting and flowering. In group 2, sonication was performed on the corms during the flowering stage at 4, 8, 12 and 16 kHz frequencies.. The changes in the contents of crocin, picrocrocin and safranal were not significantly compared to the control at 0.5, 1 and 2 kHz frequencies in the stages of sprouting and flowering of corms. While the higher frequencies (4, 8, 12 and 16 kHz) in flowering stage were affected significantly, the crocin and picrocrocin content increased 8.5% and 30%, applying the frequency of 12 and 8 kHz, respectively. Also, the effect of sound exposure time per day with the frequency of 16 kHz at 15, 30 and 60 min were investigated.. The findings showed that the corms could be affected by sounding in the different stages of growth of the corm and also in the content of secondary metabolites.

Topics: Carotenoids; Crocus; Cyclohexenes; Glucosides; Plant Extracts; Sound; Terpenes

Saffron crocus (Crocus sativus L.) has been widely grown in Iran. Its stigma is considered as the most valuable spice for which several pharmacological activities have been reported in preclinical and clinical studies, the antidepressant effect being the most thoroughly studied and confirmed. This plant part contains several characteristic secondary metabolites, including the carotenoids crocetin and crocin, and the monoterpenoid glucoside picrocrocin, and safranal. Since only the stigma is utilized industrially, huge amount of saffron crocus by-product remains unused. Recently, the number of papers dealing with the chemical and pharmacological analysis of saffron is increasing; however, there are no systematic studies on the chemical variability of the major by-products. In the present study, we harvested saffron crocus flowers from 40 different locations of Iran. The tepals and stamens were separated and subjected to qualitative and quantitative analysis by HPLC-DAD. The presence and amount of seven marker compounds, including crocin, crocetin, picrocrocin, safranal, kaempferol-3-O-sophoroside, kaempferol-3-O-glucoside, and quercetin-3-O-sophoroside were determined. The analytical method was validated for filter compatibility, stability, suitability, accuracy, precision, intermediate precision, and repeatability. Tepal and stamen samples contained three flavonol glycosides. The main constituent of the tepals was kaempferol-3-O-sophoroside (62.19-99.48 mg/g). In the stamen, the amount of flavonoids was lower than in the tepal. The amount of kaempferol-3-O-glucoside, as the most abundant compound, ranged between 1.72-7.44 mg/g. Crocin, crocetin, picrocrocin, and safranal were not detected in any of the analysed samples. Our results point out that saffron crocus by-products, particularly tepals might be considered as rich sources of flavonol glucosides. The data presented here can be useful in setting quality standards for plant parts of C. sativus that are currently considered as by-products of saffron production.

Topics: Antidepressive Agents; Carotenoids; Chromatography, High Pressure Liquid; Crocus; Cyclohexenes; Flavonoids; Flowers; Glucosides; Kaempferols; Monosaccharides; Plant Extracts; Quercetin; Terpenes; Vitamin A

Safranal and crocin, commonly derived from the oxidative cleavage reaction of zeaxanthin in plants, are two kinds of apocarotenoids with versatile functions, which were only found in limited number of plant species. In this study, both metabolites were detected and varied concomitantly with the expression of carotenoid cleavage dioxygenase (CCD) genes in Freesia hybrida, Red River® and Ambiance cultivars. The newly isolated CCD, denoted here as FhCCD2, was phylogenetically clustered with other reported saffron CCD2s. Besides, ten introns were also observed in the genomic DNA sequence of FhCCD2 and the presence of N-terminal transporter peptide suggested its plastidial sub-localization. Biochemical analysis showed that the FhCCD2 cleaved zeaxanthin at the 7, 8 and 7', 8' double bonds to generate intermediates prerequisite for the biosynthesis of safranal and crocin. Further, gene transient expression analysis showed that the promoter of FhCCD2 was functional in Ambiance as well as Red River® cultivars, even with slight variation in their promoter sequence. At present, CCD2 proteins have only been found in Freesia and Crocus genus of Iridaceae family. Phylogenetic and intron position analysis infer that CCD2 perhaps emerged after the intron loss during evolutionary process of CCD1 or their shared ancestry.

Topics: Carotenoids; Cloning, Molecular; Cyclohexenes; Dioxygenases; Iridaceae; Phylogeny; Plant Proteins; Terpenes

The main active components of saffron are crocin, crocetin, picrocrocin, and safranal. There are many studies on their cardioprotective effects, but their cardiotoxicities have not been reported. The human ether-a-go-go-related gene (hERG) K+ channels are of considerable pharmaceutical interest as the target responsible for acquired long QT syndromes. The aim of this study is to explore the effects of crocin, crocetin, picrocrocin, and safranal on the K+ channels encoded by hERG. The interaction of these components with the rapid delayed rectification of K+ currents (IKr) were studied using the perforated patch recording technique. Crocin and picrocrocin had no significant effects on IKr, but crocetin and safranal inhibited hERG K+ currents in a concentration-dependent manner, with IC50 values of 36.35 μM and 37.86 μM, respectively. The maximum inhibitory effects were 37.74 ± 4.14% and 33.74 ± 4.81%, respectively, and the effects were reversible upon washout. The results demonstrate that crocetin and safranal significantly inhibit hERG K+ current, but crocin and picrocrocin do not. This suggests that crocetin and safranal may increase the risk of cardiac arrhythmias by inhibiting IKr.

Topics: Arrhythmias, Cardiac; Carotenoids; Crocus; Cyclohexenes; ERG1 Potassium Channel; Glucosides; Humans; Phytochemicals; Terpenes; Vitamin A

The expression of biosynthesis controlling genes of crocin and safranal in saffron (Crocus sativus) can be influenced by ultrasonic waves. Sterilized saffron corms were cultured in a ½-MS medium supplemented by 2-4-D and BAP.  Saffron callus cells were treated with ultrasonic waves in a cellular suspension culture under optimal growth conditions. The samples were collected at 24 and 72 hours after treatment in three replications. The secondary metabolites were measured by high-performance liquid chromatography and the gene expression was analysed by the real-time polymerase chain reaction. Results indicate that this elicitor can influence the expressions of genes CsBCH, CsLYC and CsGT-2; the ultrasonic waves acted as an effective mechanical stimulus to the suspension cultures. The analysis of variance of the ultrasonically produced amounts of safranal and crocin indicates that there is a significant difference between once- and twice-treated samples in that the amount of safranal was the highest within the samples taken from the twice-treated suspension culture at 72 h after the ultrasound treatment, and the crocin was maximised after 24 h passed the twice-applied ultrasound treatment.

Topics: Carotenoids; Chromatography, High Pressure Liquid; Crocus; Cyclohexenes; Enzymes; Gene Expression Regulation, Plant; Plant Proteins; Real-Time Polymerase Chain Reaction; Secondary Metabolism; Terpenes; Tissue Culture Techniques; Ultrasonic Waves

Saffron is the most expensive spice in the world; so, determining optimum conditions for its processing is crucial. The most important processing stage of saffron is drying of its stigma, which should be optimized and there are no reports on reactance-window (RW) of saffron. In this research, drying of saffron with traditional, RW, and oven driers and at three temperatures of 60, 70 and 80 °C, as well as room temperature (25 °C) were studied. Regarding process duration, RW drier with 200 μm Mylar membrane and oven drier were the best methods with average drying time of 25.28 and 22.28 min, respectively. As far as the concentration of bioactive ingredients, i.e., picrocrocin, safranal, and crocin, of saffron was concerned, RW drier with Pyrex glass was better than other driers, resulting in 112.83 [Formula: see text] of picrocrocin, 51.79 [Formula: see text] of safranal, and 274.76 [Formula: see text] of crocin. The panelist most favored those saffron samples dried by RW with 300 μm Mylar membrane.

Topics: Carotenoids; Chemical Phenomena; Color; Crocus; Cyclohexenes; Desiccation; Flowers; Glucosides; Phytochemicals; Powders; Sensation; Spices; Temperature; Terpenes

Crocus sativus L. is an autumn-flowering geophyte belonging to the Iridaceae family, known for the medicinal and coloring uses of the spice from its dried stigmas. It is cultivated in countries with different pedoclimatic conditions. This paper reports on a two-year research project carried out in the Basilicata region of southern Italy on the question of how to obtain the highest performance from saffron. It considers corms from three different geographical origins - 'Sardinia', 'Abruzzo' and 'Kozani' at three different cultivation sites, namely Castelgrande (40° 46' N, 15° 26' E, 781 m a.s.l.), Genzano di Lucania (40° 50' N, 16° 08' E, 344 m a.s.l.), and Villa d'Agri (40° 22' N, 15° 48' E, 638 m a.s.l.).. The highest yields were obtained in the second year by the combination of 'Genzano di L. × Sardinia' and 'Castelgrande × Abruzzo' with 28.1 and 23.9 kg ha. This study demonstrated, through principal component analysis (PCA), that the cultivation site with higher air temperature and without excessive rain during the flowering period generated the best stigma yield with high-quality traits. © 2019 Society of Chemical Industry.

Topics: Carotenoids; Climate; Crocus; Cyclohexenes; Flowers; Glucosides; Italy; Plant Extracts; Quality Control; Rain; Temperature; Terpenes

Saffron is a kind of expensive spice and therapeutic agent. In order to establish a set of methods to evaluate the quality of saffron, High Performance Liquid Chromatography/Mass Spectrometry (HPLC/MS) were used to identify the apocarotenoids extracted from saffron stigmas. TOPSIS method was applied to evaluate the qualities of saffron. The conditions of HPLC/MS and chemical fingerprints of saffron had been established. The 14 chromatographic peaks and 13 main apocarotenoids of saffron with high reproducibility, stability and specificity were confirmed. The qualities of 40 kinds of saffron from different countries and regions were ranked.

Topics: Carotenoids; Chemical Fractionation; Chromatography, High Pressure Liquid; Crocus; Cyclohexenes; Flowers; Glucosides; Mass Spectrometry; Quality Control; Reproducibility of Results; Solvents; Spices; Terpenes

The aim of this study was to contribute to the characterization of Crocus taxa using morphological, phytochemical and genetic analysis. The styles of C. cartwrightianus, C. oreocreticus and C. laevigatus, collected in the island of Crete were compared to those of C. sativus cultivated at the region of Western Macedonia (Greece). Phytochemical analysis was done using GC-MS and HPLC methods, while ISSR markers were used for their genetic characterization. Safranal was the major volatile component of the styles of C. sativus, 4-hydroxy-2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde of C. cartwrightianus and C. oreocreticus, and isophorone of C. laevigatus. C. sativus had the highest content of crocins and picrocrocin, while C. laevigatus the lowest (only 5% of C. sativus' quantity) and negligible amount of picrocrocin. According to both the genetic and the chemical analysis, C. cartwrightianus is more related to C. oreocreticus, while C. sativus and C. laevigatus are more distinct. Concordance between the two different types of data was also confirmed by the Mantel test (r = 0.932, P = .68). This is the first thorough screening of secondary metabolites (volatile and non-volatile) and also genetic and morphological characters of wild Crocus styles simultaneously, that contributes to the identification and valorisation of genotypes with similar to C. sativus traits which may be introduced as new cultivars through breeding.

Topics: Carotenoids; Chromatography, High Pressure Liquid; Crocus; Cyclohexenes; Flowers; Gas Chromatography-Mass Spectrometry; Genetic Markers; Glucosides; Greece; Phytochemicals; Terpenes; Volatile Organic Compounds

Crocin (CRO) and safranal (SAF) are bioactive constituents of saffron (dried stigma of Crocus sativus flower), an expensive spice with medicinal properties. Aqueous extract of saffron is known for its antigenotoxic effect against environmental genotoxins/carcinogens. However, there is need to identify saffron constituents responsible for this antigenotoxic effect. The aim of our investigation was to ascertain the role of CRO and SAF as inhibitors of in vivo genotoxic stress. For this purpose, Swiss albino mice were pretreated with CRO (50-mg/kg body weight (bw))/SAF (0.025- and 0.25-ml/kg bw) by gavage for 2 days. Thereafter, the pretreated mice were exposed to the genotoxic agents: (1) gamma radiation (GR; 2 Gy), (2) urethane (URE; 800 mg/kg) and (3) procarbazine (PCB; 60 mg/kg). In addition, CRO (50 mg/kg) was co-administered with the nitrosation reaction mixture of methylurea (MU; 300-mg/kg bw) + sodium nitrite (15 mg/kg) which can form N-nitroso-N-MU in the stomach. Genotoxic damage was measured by performing the bone marrow micronucleus test. Results obtained demonstrated significant reductions in the incidence of micronucleated polychromatic erythrocytes in the bone marrow of mice pretreated with CRO/SAF before exposure to the above DNA damaging agents, GR, URE and PCB. Co-administration of CRO with the nitrosation reaction mixture led to significant decrease in genotoxicity when compared to nitrosation reaction mixture alone. Histopathological studies revealed that these saffron constituents reduced testicular cell damage induced by the test genotoxins. The cell-free DNA-nicking assay using pBR322 DNA showed significant protective effects of CRO against hydroxyl radical-induced strand breaks.

Topics: Animals; Antimutagenic Agents; Antineoplastic Agents; Carotenoids; Crocus; Cyclohexenes; DNA Damage; Gamma Rays; Male; Mice; Micronucleus Tests; Procarbazine; Terpenes; Testis; Urethane

The present study illustrates a simple and practical way to produce an adequate delivery system of bioactive compounds of saffron by protein-polysaccharide complex. Frist, crocin, safranal, and picrocrocin were loaded in nanodroplets (<100nm) by using water in oil (W/O) microemulsions contain 5, and 10% aqueous saffron extract as a dispersed phase. These microemulsions were then covered with whey protein concentrate (WPC)-maltodextrin or WPC-pectin-maltodextrin through water in oil in water (W/O/W) multiple emulsions. The stability and release of loaded crocin, safranal, and picrocrocin in multiple emulsions were investigated during 22days storage. The produced multiple emulsion by WPC-pectin-maltodextrin along with 5% inner aqueous phase showed a high stability and low release of encapsulated compounds over time. This emulsion also provided a high protection of crocin, safranal, and picrocrocin in the gastric condition.

Topics: Carotenoids; Crocus; Cyclohexenes; Emulsions; Glucosides; Pectins; Plant Extracts; Polysaccharides; Terpenes; Water; Whey Proteins

A microwave-assisted extraction method was optimised for the recovery of bioactive compounds from Crocus sativus L. stigmas with the use of water/ethanol mixture. HPLC-DAD was employed to evaluate the extraction parameters, in particular, solvent type and volume, and the duration of the procedure. Microwave-assisted extraction enhanced the recovery of the active principles, limiting extraction time and solvent waste. Moreover, NIR experiments were performed in order to compare spectra in pseudo-absorbance of Saffron samples with different geographical origins through the application of the chemometric techniques. Moreover, the biological evaluation of crocin 1, safranal and its semisynthetic derivatives as selective inhibitors of five isoforms of human carbonic anhydrase was also explored.

Topics: Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Carotenoids; Chromatography, High Pressure Liquid; Crocus; Cyclohexenes; Geography; Glucosides; Humans; Limit of Detection; Plant Extracts; Reproducibility of Results; Spectroscopy, Near-Infrared; Terpenes

Crocus sativus belongs to Iridaceae family and is the only plant species which produces apocarotenoids like crocin, picrocrocin, and safranal in significant quantities. Besides their organoleptic properties, Crocus apocarotenoids have been found to possess remarkable pharmacological potential. Although apocarotenoid biosynthetic pathway has been worked out to a great degree, but the mechanism that regulates the tissue and developmental stage-specific production of Crocus apocarotenoids is not known. To identify the genes regulating apocarotenoid biosynthesis in Crocus, transcriptome wide identification of zinc-finger transcription factors was undertaken. 81 zinc-finger transcription factors were identified which grouped into eight subfamilies. C2H2, C3H, and AN20/AN1 were the major subfamilies with 29, 20, and 14 members, respectively. Expression profiling revealed CsSAP09 as a potential candidate for regulation of apocarotenoid biosynthesis. CsSAP09 was found to be highly expressed in stigma at anthesis stage corroborating with the accumulation pattern of apocarotenoids. CsSAP09 was nuclear localized and activated reporter gene transcription in yeast. It was highly induced in response to oxidative, salt and dehydration stresses, ABA and methyl jasmonate. Furthermore, upstream region of CsSAP09 was found to contain stress and light responsive elements. To our knowledge, this is the first report on the study of a gene family in C. sativus and may provide basic insights into the putative role of zinc finger genes. It may also serve as a valuable resource for functional characterization of these genes aimed towards unraveling their role in regulation of apocarotenoid biosynthesis.

Topics: Arabidopsis; Base Sequence; Carotenoids; Cloning, Molecular; Crocus; Cyclohexenes; Gene Expression Profiling; Gene Expression Regulation, Plant; Genome, Plant; Glucosides; Plant Proteins; Promoter Regions, Genetic; Sequence Analysis, DNA; Terpenes; Transcription Factors; Transcriptional Activation; Transcriptome; Zinc Fingers

Saffron (Crocus sativus) is a widely used food additive for its color and taste. Crocin and safranal are two main components of this plant. Numerous studies are underway to introduce saffron and its active ingredients as pharmacological agents. Safety assessments of these compounds are important parts of this endeavor. In this study, the effects of crocin and safranal administrations during embryogenesis have been investigated in mice. A total of 75 BALB/c pregnant mice were divided into six experimental and control groups. Four experimental groups received intraperitoneal injection of crocin (200 mg/kg or 600 mg/kg) daily or safranal (0.075 ml/kg or 0.225 ml/kg) on gestational days (GDs) 6 to 15. Control groups received normal saline or paraffin as solvents of crocin and safranal. Dams were dissected on GD18 and embryos were collected. Routine maternal and fetal parameters were recorded. Macroscopic observation of external malformations was also performed. Fetuses were then selected for double skeletal staining with alizarin red and alcian blue. All experimental groups caused significant decrease in length and weight of fetuses when compared with the control groups and revealed malformations such as minor skeletal malformations, mandible and calvaria malformations, and growth retardation. Minor skeletal malformations were the most commonly observed abnormality, which were statistically significant when compared with the control groups (p < 0.05). The severities of malformations were comparable in the crocin- and safranal-treated groups. This study suggests that crocin or safranal can induce embryonic malformations when administered in pregnant mice. Due to the wide use of saffron, further elaborate studies to understand the malformation mechanisms of these ingredients are recommended.

Topics: Animals; Body Weight; Carotenoids; Crocus; Cyclohexenes; Female; Fetus; Mice; Mice, Inbred BALB C; Organogenesis; Pregnancy; Teratogens; Terpenes

The limited arsenal of synthetic antifungal agents and the emergence of resistant Candida strains have prompted the researchers towards the investigation of naturally occurring compounds or their semisynthetic derivatives in order to propose new innovative hit compounds or new antifungal combinations endowed with reduced toxicity. We explored the anti-Candida effects, for the first time, of two bioactive compounds from Crocus sativus stigmas, namely crocin 1 and safranal, and some semisynthetic derivatives of safranal obtaining promising biological results in terms of minimum inhibitory concentration/minimum fungicidal concentration (MIC/MFC) values, synergism and reduction in the germ tube formation. Safranal and its thiosemicarbazone derivative 5 were shown to display good activity against Candida spp.

Topics: Antifungal Agents; Candida albicans; Carotenoids; Crocus; Cyclohexenes; Dose-Response Relationship, Drug; Drug Synergism; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Terpenes

One hundred and forty-four Italian saffron samples produced in the years from 2009 to 2015 in five distinct areas located in four different regions, Abruzzo (L'Aquila), Tuscany (Florence), Umbria (Cascia and Città della Pieve) and Sardinia, have been analysed by high-performance liquid chromatography with diode array detection. Intensities of the chromatographic peaks attributed to crocins, safranal, picrocrocin and its derivatives and flavonoids were considered as variables in linear discriminant analysis to attempt geographical classification. The results revealed that spices produced at different sites of the Italian territory can be discriminated with good accuracy. The differentiation of saffron cultivated in Sardinia from those produced in Central Italy was mainly attributed to different contents of the most abundant crocins. Good differentiation of spices produced in close sites of Central Italy was also observed, 88% of validation samples being correctly classified; some minor crocins are responsible for such discrimination.

Topics: Carotenoids; Chromatography, High Pressure Liquid; Crocus; Cyclohexenes; Discriminant Analysis; Flavonoids; Glucosides; Italy; Plant Extracts; Terpenes

Ischemia-reperfusion (IR) injury of the liver is an unresolved problem that occurs during certain surgical approaches, including hepatic, cardiac and aortic operations. In this study we aimed to investigate whether crocin and safranal had protective effects on liver IR injury induced in an infrarenal aortic clamping (IRAC) model. Male Wistar-Albino rats (n=32) were divided into four groups with 8 animals each as follows: Sham, IR, IR+crocin, and IR+safranal. The infrarenal aorta (IRA) was clamped for 60min for the ischemic period and allowed to reperfuse for 120min. Blood and tissue samples were collected for biochemical, histological and immunohistological analysis. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were found to be significantly higher in the IR group than the sham group (respectively; p=0.015, p<0.001). There were significant differences between the IR group and the IR+crocin group or the IR+safranal group in AST levels (respectively; p=0.02, p<0.001). ALT showed a significant decrease in the IR+crocin group compared to the IR group (p<0.05). We also observed histopathological changes among the groups. Bax and Caspase-3 expression in the IR group was remarkably higher than in the other groups. Caspase-3 and Bax expression in the IR+crocin and the IR+safranal groups were significantly lower than in the IR group. Nevertheless, there were no significant differences in BCL2 expression among the groups. IRAC is a cause of IR injury in the liver. This study showed that crocin and safranal have protective effects on IR induced liver injury.

Topics: Alanine Transaminase; Animals; Arterial Occlusive Diseases; Aspartate Aminotransferases; bcl-2-Associated X Protein; Carotenoids; Caspase 3; Cyclohexenes; Immunohistochemistry; Kidney; Liver; Liver Function Tests; Male; Rats, Wistar; Reperfusion Injury; Terpenes

n/a.

Topics: Anti-Anxiety Agents; Antioxidants; Biological Products; Cardiovascular Agents; Carotenoids; Color; Crocus; Cyclohexenes; Flowers; Food Contamination; Glucosides; Humans; Odorants; Proteomics; Quality Control; Spices; Taste; Terpenes

Safranal and crocin are biologically active compounds isolated from Crocus sativus L., commonly known as saffron. Clinical trials confirm that saffron has antidepressant effect, thus being a potential valuable alternative in the treatment of depression. The aim of the present study was to determine, whether systemic administration of safranal and crocin can influence the metabolic activity of CYP3A, CYP2C11, CYP2B, and CYP2A in rat liver microsomes (RLM). The experiments were carried out on male Wistar albino rats intragastrically administered with safranal (4, 20, and 100 mg/kg/day) or with intraperitoneal injections of crocin (4, 20, and 100 mg/kg/day). Our results demonstrate the ability of safranal and crocin to increase the total protein content and to change the metabolic activity of several CYP enzymes assessed as CYP specific hydroxylations of testosterone in RLM. Crocin significantly decreased the metabolic activity of all selected CYP enzymes, while safranal significantly increased the metabolic activity of CYP2B, CYP2C11 and CYP3A enzymes. Therefore, both substances could increase the risk of interactions with co-administered substances metabolized by cytochrome P450 enzymes.

Topics: Animals; Carotenoids; Crocus; Cyclohexenes; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Enzyme Activation; Male; Microsomes, Liver; Plant Extracts; Rats; Rats, Wistar; Terpenes

Saffron's quality depends on the concentration of secondary metabolites, such as crocins, picrocrocin and safranal. The aim of this research was to evaluate the influence of drying conditions on the secondary metabolite contents of saffron produced in the area of Cascia, in central Italy. Different aliquots of the same saffron sample were subjected to various dehydration conditions and analysed by UV-Vis spectrophotometry to determine crocins, picrocrocin and safranal.. Safranal was also analysed by high resolution gas chromatography, while the crocins and picrocrocin were determined by high-performance liquid chromatography with diode array and mass spectrometric detectors. The results of chromatographic analyses showed that the samples dried in the milder conditions had the lowest content of secondary metabolites. Moreover the sample dried at 60°C for 55min presented the highest contents of trans-crocin-4 and picrocrocin, while safranal was most represented in saffron dried at 55°C for 95min.

Topics: Carotenoids; Chromatography, Gas; Chromatography, High Pressure Liquid; Crocus; Cyclohexenes; Glucosides; Italy; Plant Extracts; Secondary Metabolism; Terpenes

Saffron (Crocus sativus L.) is one of the most expensive medicinal and aromatic plants in the world. Due to the excessive application of chemical fertilisers in saffron farms and alkalinity of most cultivated soils, split foliar fertilisation has been suggested. The primary goal of this study was to propose split foliar fertilisation as a technique in increasing the quality and quantity of active constituents in saffron. HPLC analysis was used to quantify the most important saffron components; crocins (colour), picrocrocin (taste), and safranal (odour). This study was carried out in Kashmar, Iran, to determine the effect of split foliar fertilisations on quality and quantity of saffron in 2011 and 2012. A split-plot design experiment based on randomised complete block with three replications was conducted to examine three fertiliser types in three regimes for split foliar fertilisation.. Statistical analysis showed that split foliar fertilisation and the fertiliser type significantly increased saffron yield, number of flowers and crocin; whereas it decreased the picrocrocin and safranal content of the saffron stigmas (P < 0.05).. Overall, split foliar fertilisation increased saffron yield and colour but decreased the taste and the odour of saffron.

Topics: Agriculture; Carotenoids; Chromatography, High Pressure Liquid; Crocus; Cyclohexenes; Fertilizers; Flowers; Glucosides; Humans; Iran; Plant Extracts; Plant Leaves; Terpenes

Crocin, a main constituent of Crocus sativus L (saffron), has been found to inhibit the growth of K-562 human chronic myelogenous leukemia (CML) cells expressing Bcr-Abl protein tyrosine kinase activity. The aim of our study is to investigate the ability of the bioactive saffron's constituents, crocin (CRC) and safranal (SFR), to inhibit the Bcr-Abl protein activity employing an in silico approach, as well as the in vitro effect of these compounds on K-562 growth and gene expression of Bcr-Abl. In silico molecular docking studies revealed that mostly SFR can be attached to Bcr-Abl protein, positioned inside the protein's binding cavity at the same place with the drug used in the treatment of CML, imatinib mesylate (IM). The predicted polar interactions and hydrophobic contacts constructing a hydrophobic cavity inside the active site, explain the observed inhibitory activity. Cytotoxicity experiments showed that SFR and CRC mediate cytotoxic response to K562 cells. In vitro studies on the expression of Bcr-Abl gene revealed that SFR and in a lesser degree IM inhibited the expression of the gene, while in contrast CRC induced an increase. The ultimate goal was to evaluate the existence of a potential antitumor activity of saffron's constituents SFR and CRC.

Topics: Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Benzamides; Carotenoids; Cell Line, Tumor; Computer Simulation; Crocus; Cyclohexenes; Fusion Proteins, bcr-abl; Gene Expression; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Docking Simulation; Piperazines; Pyrimidines; Terpenes

Saffron, the dried stigmas of Crocus sativus L., is used as a condiment spice. The major bioactive compounds are crocins, picrocrocin and safranal, which are responsible for the sensory profile of saffron (color, flavor and aroma, respectively), and also health-promoting properties. In this paper, the effect on the bioactive compounds of different cooking times in boiling water at 100 °C in samples of Saffron from La Mancha (safranal, picrocrocin, trans-crocin 4, cis-crocin 4 and trans-crocin 3) was investigated. Performance characteristics of High Performance Liquid Chromatography with Variable Wavelength Detector method, parameters of linearity, limits of detection and quantification are reported. High Performance Liquid Chromatography-Photo Diode Array-Mass Spectrometry was used as a confirmatory technique in crocins identification. When the samples are subjected to different cooking times, they present different behaviors, depending on the bioactive compound. In this way, no changes were observed in the concentration of picrocrocin, while heat culinary treatment adversely affects the concentrations of crocins and safranal.

Topics: Carotenoids; Chromatography, High Pressure Liquid; Cooking; Crocus; Cyclohexenes; Flowers; Glucosides; Humans; Mass Spectrometry; Plant Extracts; Spices; Terpenes

Crocin and safranal are the active substances of saffron and have many biological properties. In the present study, we compared the effects of crocin, safranal and diclofenac on local inflammation and its induced pain in rats.. Local inflammation was induced by intraplantar (ipl) injection of carrageenan (100 μl, 2%). Paw thickness was measured before and after carrageenan injection. Inflammatory pain responses including cold allodynia, mechanical allodynia and hyperalgesia were assessed using acetone spray and von Frey filament tests, respectively. The number of neutrophils in inflammatory zone was counted 6.5 h after injection of carrageenan.. Carrageenan produced edema, cold allodynia, mechanical allodynia and hyperalgesia and caused neutrophil infiltration in paw tissues. Crocin at doses of 25, 50 and 100 mg/kg, safranal at doses of 0.5, 1 and 2 mg/kg and diclofenac (as a reference drug) at a dose of 10 mg/kg attenuated edema, suppressed inflammatory pain responses and decreased the number of neutrophils.. The present study showed anti-inflammatory and antinociceptive activities for crocin, safranal and diclofenac in carrageenan model of local inflammation and inflammatory pain.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carotenoids; Carrageenan; Cyclohexenes; Diclofenac; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Hyperalgesia; Inflammation; Male; Neutrophil Infiltration; Pain; Pain Threshold; Rats; Rats, Wistar; Terpenes; Time Factors

Saffron is an expensive spice, cultivated in many regions of the world. Its chief metabolites include crocins, which are responsible for the coloring ability, safranal, which is the main essential oil constituent, and picrocrocin which is the main bitter constituent of the spice. A simple micellar capillary electrochromatographic (MEKC) method capable of quantifying all three types of main constituents was established. The pH, sodium dodecyl sulphate (SDS) content and electrolyte concentration of the background electrolyte was optimized. A simple extraction protocol was developed which can extract all metabolites of different polarity from the saffron stigmas. Optimal background electrolyte composed of 20 mM disodium phosphate, 5mM sodium tetraborate, 100 mM SDS, pH was set 9.5. Optimal extracting solvent was the background electrolyte, incubated with the sample for 60 min. The proposed method allows quantification of picrocrocin, safranal, crocetin- Di-(β-D-gentiobiosyl) ester and crocetin (β-D-glycosyl)-(β-D-gentiobiosyl) ester within 17.5 min, with limit of detection values ranging from 0.006 to 0.04 mg/ml, from a single stigma.

Topics: Carotenoids; Chromatography, Micellar Electrokinetic Capillary; Crocus; Cyclohexenes; Electrolytes; Glucosides; Hydrogen-Ion Concentration; Limit of Detection; Micelles; Plant Extracts; Sodium Dodecyl Sulfate; Solvents; Terpenes

The current study was designed to evaluate therapeutic potential of systemically administered ethanolic and aqueous extracts of saffron as well as its bioactive ingredients, safranal and crocin, in chronic constriction injury (CCI)-induced neuropathic pain in rats. The von Frey filaments, acetone drop, and radiant heat test were performed to assess the degree of mechanical allodynia, thermal allodynia and thermal hyperalgesia respectively, at different time intervals, i.e., one day before surgery and 3, 5, 7 and 10 days post surgery. The ambulatory behavior was evaluated using the open field test. A 7-day treatment with the ethanolic and aqueous extracts (50,100 and 200 mg/kg, i.p.) and safranal (0.025, 0.05 and 0.1 mg/kg, i.p.), attenuated the behavioral symptoms of neuropathic pain in a dose dependent manner. Crocin even at the high dose (50 mg/kg) failed to produce any protective role. However, gabapentine (100 mg/kg) as a reference drug significantly alleviated all behavioral manifestations of neuropathic pain compared to control group. In conclusion, the results of this study suggest that ethanolic and aqueous extracts of saffron as well as safranal could be useful in treatment of different kinds of neuropathic pains and as an adjuvant to conventional medicines.

Topics: Acetone; Amines; Analgesics; Animals; Behavior, Animal; Carotenoids; Constriction; Crocus; Cyclohexanecarboxylic Acids; Cyclohexenes; Disease Models, Animal; Dose-Response Relationship, Drug; Gabapentin; gamma-Aminobutyric Acid; Hot Temperature; Hyperalgesia; Male; Neuralgia; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Terpenes; Walking

In this study, the effect of crocin and safranal was studied against subacute toxicity of diazinon (DZN) on hematological and genotoxicity indices in rats. The rats were divided into 16 groups consisted of 6 rats in control, diazinon, vitamin E, vitamin E and DZN, crocin (3 doses), crocin (3 doses) and DZN, safranal (3 doses), safranal (3 doses) and DZN groups. Vitamin E (200 IU/kg), safranal at doses 0.025, 0.05 and 0.1 ml/kg and crocin at doses 50, 100 and 200 mg/kg were injected intraperitoneally to rats three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. Hematological parameters were evaluated at the end of 4 weeks. The evaluation of genotoxicity was done using the micronucleus assay. Vitamin E and, at lower doses, safranal (0.025 and 0.05 ml/kg) and crocin (50 mg/kg) restored the reduction of red blood cell, hemoglobin and hematocrit indices induced by DZN. These agents at some doses also prevented the reduction in platelets counts indices in diazinon treated group. A significant increase in reticulocyte was induced by diazinon. Vitamin E, safranal (0.025 or 0.05 ml/kg) and all doses of crocin decreased this effect of diazinon. In all doses vitamin E, crocin and safranal did not inhibit the effect of diazinon on RBC cholinesterase activity. A significant increase in micronucleus indices was seen with diazinon. Vitamin E, safranal and crocin could not prevent this genotoxicity. This study showed that vitamin E, safranal and crocin (without effects on cholinesterase) reduced diazinon hematological toxicity, but they did not prevent the genotoxicity induced by diazinon.

Topics: Animals; Blood Platelets; Carotenoids; Crocus; Cyclohexenes; Diazinon; DNA Damage; Erythrocytes; Hematocrit; Hematologic Tests; Hemoglobins; Insecticides; Male; Micronucleus Tests; Plant Extracts; Rats; Rats, Wistar; Reticulocytes; Stress, Physiological; Terpenes; Vitamin E; Vitamins

In the present study, the effects of an ethanol and aqueous extract of saffron Crocus sativus and its constituents safranal and crocin on the stress-induced reduction in food intake, weight gain and anorexic time in mice were investigated. Male albino mice (20-25 g) were irregularly exposed to a trial of electroshock stress for 7 days. Then, the anorexic time as well as the animal's food intake and weight were recorded. In addition, blood samples were obtained on days 1 and 7 for corticosterone determination. Intraperitoneal (i.p.) administration of the aqueous but not the ethanol extract (10, 50 and 100 mg/kg) significantly reduced the anorexic time. The results were similar for crocin (1, 5 and 10 mg/kg; i.p.). In addition, a reduction in weight gain was observed in the controls as well as in the groups that received alcohol extract or safranal. However, this was not observed in animals treated with aqueous extract or crocin. The plasma corticosterone level did not increase in the aqueous extract and crocin treated animals. It can be concluded that the saffron aqueous extract and its constituent crocin reduce side effects of electroshock stress in mice.

Topics: Animals; Anorexia; Body Weight; Carotenoids; Corticosterone; Crocus; Cyclohexenes; Electroshock; Energy Intake; Ethanol; Male; Mice; Plant Extracts; Stress, Physiological; Terpenes; Weight Loss

Crocus sativus L. has been shown to interact with the opioid system. Thus, the effects of aqueous and ethanolic extracts of stigma and its constituents were evaluated on morphine-withdrawal syndrome in mice. Dependence was induced using subcutaneous (s.c.) injections of morphine for 3 days. On day 4, morphine was injected 0.5 h prior the interaperitoneal (i.p.) injections of the extracts, crocin, safranal, clonidine (0.3 mg/kg) or normal saline. Naloxone was injected (5 mg/kg i.p.) 2 h after the final dose of morphine and the number of episodes of jumping during 30 mm was considered as the intensity of the withdrawal syndrome. Clonidine, the aqueous and ethanolic extracts of saffron reduced the jumping activity. Safranal was injected (s.c.) 30 mm prior and 1 and 2 h after the injection of morphine. It potentiated some signs of withdrawal syndrome. The aqueous extract decreased the movement in all of the doses (80, 160, 320 mg/kg) and the ethanolic extract decreased it in the dose of 800 mg/kg in open field test. But crocin and the dose of 400 mg/kg ethanolic extract showed no effect on activity in this test. It is concluded that the extracts and crocin may have interaction with the opioid system to reduce withdrawal syndrome.

Topics: Animals; Carotenoids; Clonidine; Crocus; Cyclohexenes; Male; Mice; Morphine; Morphine Dependence; Motor Activity; Naloxone; Plant Extracts; Substance Withdrawal Syndrome; Terpenes

In this study, the effects of saffron (Crocus sativus) stigma aqueous extract and two active constituents, crocin and safranal, were investigated on blood pressure of normotensive and desoxycorticosterone acetate-induced hypertensive rats. Three doses of crocin (50, 100 and 200 mg/kg), safranal (0.25, 0.5 and 1 mg/kg) and the aqueous extract (2.5, 5 and 10 mg/kg) were administered intravenously in different groups of normotensive and hypertensive animals and their effects on mean arterial blood pressure (MABP) and heart rate (HR) were evaluated. The aqueous extract of saffron stigma, safranal and crocin reduced the MABP in normotensive and hypertensive anaesthetized rats in a dose-dependent manner. For example, administrations of 10 mg/kg of aqueous extract, 1 mg/kg of safranal and 200 mg/kg of crocin caused 60 +/- 8.7, 50 +/- 5.2 and 51 +/- 3.8 mmHg reductions in MABP, respectively. It can be concluded that the aqueous extract of saffron stigma has hypotensive properties which appear to be attributable, in part, to the actions of two major constitutes of this plant, crocin and safranal. It seems that safranal is more important than crocin for lowering down blood pressure of rats.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Carotenoids; Crocus; Cyclohexenes; Desoxycorticosterone; Flowers; Heart Rate; Hypertension; Male; Plant Extracts; Rats; Rats, Wistar; Terpenes

Formation of toxic amyloid structures is believed to be associated with various late-onset neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The fact that many proteins in addition to those that are associated with clinical conditions have the potential to form amyloid fibrils in vitro provides opportunities for studying the fundamentals of protein aggregation and amyloid formation in model systems. Accordingly, considerable interest and effort has been directed toward developing small molecules to inhibit the formation of fibrillar assemblies and their associated toxicities. In the present study, we investigated the inhibitory effect of crocin and safranal, two principal components of saffron, on fibrillation of apo-alpha-lactalbumin (a-alpha-LA), used as a model protein, under amyloidogenic conditions. In the absence of any ligand, formation of soluble oligomers became evident after 18 h of incubation, followed by subsequent appearance of mature fibrils. Upon incubation with crocin or safranal, while transition phase to monomeric beta structures was not significantly affected, formation of soluble oligomers and following fibrillar assemblies were inhibited. While both safranal and crocin had the ability to bind to hydrophobic patches provided in the intermediate structures, and thereby inhibit protein aggregation, crocin was found more effective, possibly due to its simultaneous hydrophobic and hydrophilic character. Cell viability assay indicated that crocin could diminish toxicity while safranal act in reverse order.

Topics: Amyloid; Animals; Benzothiazoles; Biological Assay; Carotenoids; Cattle; Circular Dichroism; Congo Red; Crocus; Cyclohexenes; Lactalbumin; Microscopy, Atomic Force; Molecular Weight; Particle Size; PC12 Cells; Protein Structure, Secondary; Protein Structure, Tertiary; Rats; Spectrometry, Fluorescence; Terpenes; Thiazoles

In this study, the effects of crocin and safranal were studied against sub-acute toxicity of diazinon (DZN) on specific biomarkers, biochemical indices and enzymes levels in rats. Vitamin E (200 IU/kg), safranal at doses 0.025, 0.05 and 0.1 ml/kg and crocin at doses 50, 100 and 200mg/kg were injected intraperitoneally three times per week alone or with DZN (20mg/kg/day, orally) for 4 weeks. The parameters were evaluated at the end of 4 weeks. Diazinon did not change serum urea, creatinine, cholesterol, triglyceride, total and direct bilirubin levels. Total protein and albumin concentrations were decreased by diazinon. Crocin, safranal and vitamin E prevented the effect of diazinon on some biochemical indices and enzymes levels. The levels of serum TNF-alpha, direct 8-iso-prostaglandin F(2 alpha) and soluble protein-100 beta (S100 beta) were increased significantly by diazinon. The augmentation of direct 8-iso-prostaglandin F(2 beta) and S100 beta levels by diazinon was significantly decreased by crocin, safranal and vitamin E. TNF-alpha level was significantly decreased in diazinon plus crocin 50 and 100mg/kg treated groups compared to the diazinon group. This study showed that vitamin E, safranal and crocin could prevent diazinon induced enzymes elevation and augmentation of some specific biomarkers.

Topics: Animals; Antioxidants; Biomarkers; Carotenoids; Cyclohexenes; Diazinon; Enzymes; Injections, Intraperitoneal; Insecticides; Liver Function Tests; Male; Rats; Rats, Wistar; Terpenes; Vitamin E

Saffron stigma (Crocus sativus L.) is used for insomnia and anxiety in traditional medicine. In this study, the anxiolytic and hypnotic effects of saffron aqueous extract and its constituents, crocin and safranal, were studied in mice. Agents were administered intraperitoneally in mice before the experiments for the evaluation of hypnotic activity (induced by sodium pentobarbital, 30 mg/kg, i.p.), anxiolytic activity (elevated plus maze test), locomotor activity (open field test) and motor coordination (Rotarod test). The aqueous extract reduced the locomotor activity dose dependently. At low doses, saffron showed a significant increase in the time on the open arms of the maze. When using the Rotarod method, the aqueous extract showed considerable effect on motor coordination of the mice. In the hypnotic test, only a dose of 0.56 g/kg of saffron increased the total sleep. Crocin showed no anxiolytic, hypnotic or myorelaxation effects. Safranal, in higher doses, 0.15 and 0.35 mL/kg, showed anxiolytic effects. Safranal increased the total sleep time dose dependently. This constituent at lower doses (0.05 and 0.15 mL/kg) decreased some locomotion activity parameters. Safranal demonstrated no effects on motor coordination. The results showed that saffron aqueous extract and safranal have anxiolytic and hypnotic effects.

Topics: Animals; Anti-Anxiety Agents; Carotenoids; Crocus; Cyclohexenes; Dose-Response Relationship, Drug; Flowers; Hypnotics and Sedatives; Male; Maze Learning; Mice; Motor Activity; Pentobarbital; Plant Extracts; Rotarod Performance Test; Terpenes

In this study, the aphrodisiac activities of Crocus sativus stigma aqueous extract and its constituents, safranal and crocin, were evaluated in male rats. The aqueous extract (80, 160 and 320mg/kg body wt.), crocin (100, 200 and 400mg/kg body wt.), safranal (0.1, 0.2 and 0.4ml/kg), sildenafil (60mg/kg body wt., as a positive control) and saline were administered intraperitoneally to male rats. Mounting frequency (MF), intromission frequency (IF), erection frequency (EF), mount latency (ML), intromission latency (IL) and ejaculation latency (EL) were the factors evaluated during the sexual behavior study. Crocin, at all doses, and the extract, especially at doses 160 and 320mg/kg body wt., increased MF, IF and EF behaviors and reduced EL, IL and ML parameters. Safranal did not show aphrodisiac effects. The present study reveals an aphrodisiac activity of saffron aqueous extract and its constituent crocin.

Topics: Animals; Aphrodisiacs; Carotenoids; Crocus; Cyclohexenes; Female; Male; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Sexual Behavior, Animal; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Terpenes

Extracts from saffron, the dried stigmata from Crocus sativus L., are being used more and more in preclinical and clinical trials for the treatment of cancer and depression. Because of the known quality problems of saffron, HPLC methods on RP(18) 2.5 microm and monolithic RP(18) material have been developed and validated for quality control including the quantification of crocins 1 to 5, crocetin, picrocrocin and the degradation products, the CIS-crocins. Additionally, a GC-MS method has allowed detection and quantification of the volatile compounds from the pentane extract of saffron. Both systems together allowed the comprehensive characterisation of saffron herbal material and extracts for clinical/preclinical trials. For effective preparation of the respective reference standards, a fast centrifugal partition chromatography (FCPC) method was developed allowing the quick isolation of crocins 1, 2, 5 and picrocrocin in good yields. Using these chromatographic methods and the reference standards, a representative survey of saffron from the global market indicated a high variability of quality, especially concerning the amounts of volatile compounds in saffron samples. A specification for high-quality saffron of >20% crocins, >6% picrocrocin and not less than 0.3% of volatiles, calculated as sum of safranal, isophorone and ketoisophorone, was developed. Because no detailed pharmacological studies are available to explain the clinical effects of saffron for the treatment of cancer and depression, receptor binding studies were performed. Saffron extracts and crocetin had a clear binding capacity at the PCP binding side of the NMDA receptor and at the sigma(1) receptor, while the crocins and picrocrocin were not effective. These data could give biochemical support for the above-mentioned pharmacological effects of saffron.

Topics: Carotenoids; Crocus; Cyclohexanones; Cyclohexenes; Flowers; Glucosides; Plant Extracts; Quality Control; Receptors, N-Methyl-D-Aspartate; Receptors, sigma; Reference Standards; Sigma-1 Receptor; Terpenes; Vitamin A

The antitussive activity of Crocus sativus stigma and petal extracts and its components, safranal and crocin, was evaluated using the nebolized solution of citric acid 20% in guinea pigs. The extract and agents were injected intraperitoneally. The ethanolic extract of C. sativus (100-800 mg/kg) and safranal (0.25-0.75 ml/kg) reduced the number of cough. The ethanolic and aqueous extracts of petal and crocin did not show antitussive activity.

Topics: Animals; Antitussive Agents; Carotenoids; Citric Acid; Cough; Crocus; Cyclohexenes; Female; Flowers; Guinea Pigs; Injections, Intraperitoneal; Male; Phytotherapy; Plant Extracts; Terpenes

As indicated in ancient Iranian medical books, Crocus sativus has therapeutic effects on respiratory diseases. The relaxant effect of this plant has been observed also on smooth muscles in previous studies. Therefore, in this study the relaxant effects of aqueous-ethanolic extracts of C. sativus and one of its main constituents, safranal, were examined on guinea-pig tracheal chains. The relaxant effects of four cumulative concentrations of aqueous-ethanolic extract (0.15, 0.3, 0.45, and 0.60 g %) and safranal (0.15, 0.30, 0.45, and 0.60 mL 0.2 mg mL(-1) solution) in comparison with saline, as negative control, and four cumulative concentrations of theophylline (0.15, 0.30, 0.45, and 0.60 mM), as positive control, were examined using guinea-pig precontracted tracheal chains. The tracheal chains had been precontracted by three different methods. Group 1 had been precontracted using 10 microM methacholine. The other two groups had been precontracted using 60 mM KCl at two different conditions: non-incubated tissues (group 2) and tissues incubated with 1 microM propranolol, 1 microM chlorpheniramine and 1 microM atropine (group 3) (for each group, n = 6). In group 1 all concentrations of theophylline, extract and safranal showed significant relaxant effects compared with saline (P < 0.05 to P < 0.001). In group 2 theophylline, extract and safranal showed concentration-dependent relaxant effects also compared with saline (P < 0.05 to P < 0.001 for different concentrations except two low concentrations of safranal). However, in group 3 the extracts of C. sativus showed a weak relaxant effect (P < 0.05 only for the highest concentration). The effects of the last concentration of safranal (0.60 mL 0.2 mg mL(-1) solution) in group 1, and all its concentrations in group 2 were significantly lower than those of theophylline (P < 0.05 to P < 0.001). In addition, the effects of safranal 0.45 and 0.60 mL 0.2 mg mL(-1) solution in groups 1 and 2 were significantly lower than that of C. sativus extract. There were significant correlations between the relaxant effects and concentrations for extract, safranal and theophylline in all experimental groups (P < 0.001 for all cases). These results showed a potent relaxant effect of C. sativus on tracheal chains of guinea-pigs that was comparable to or even higher than that of theophylline at the concentrations used. The results indicated that safranal was, at least in part, responsible for the relaxant effect of C. sativus.

Topics: Animals; Bronchi; Bronchodilator Agents; Carotenoids; Crocus; Cyclohexenes; Dose-Response Relationship, Drug; Ethanol; Guinea Pigs; Male; Muscle Relaxation; Muscle, Smooth; Phytotherapy; Plant Extracts; Sodium Chloride; Terpenes; Theophylline; Water

Safranal is the compound most responsible for the aroma of saffron spice and is, together with the suite of crocin pigments, the major determinant of the product quality. The content of safranal and pigments in saffron is determined by the method of postharvest treatment of the Crocus stigmas. A range of drying treatments involving different temperatures, with or without air flow, was applied to stigmas from three harvest dates. Dual solvent extractions combined with quantitative measurement using GC and HPLC-UV-vis techniques were used to analyze the secondary metabolite contents of the products. It was demonstrated that these methods overcame the previously reported problems in measuring the concentration of both pigments and safranal in saffron caused by the very different polarities and thus solubilities of these compounds. The results showed that a brief (20 min) initial period at a relatively high temperature (between 80 and 92 degrees C) followed by continued drying at a lower temperature (43 degrees C) produced saffron with a safranal content up to 25 times that of saffron dried only at lower temperatures. Evidence was provided suggesting that drying with significant air flow reduced the safranal concentration. The results, moreover, indicated that high-temperature treatment had allowed greater retention of crocin pigments than in saffron dried at intermediate temperatures (46-58 degrees C). The biochemical implications of the various treatments are discussed in relation to the potential for optimizing color and fragrance quality in the product.

Topics: Air Movements; Carotenoids; Color; Crocus; Cyclohexenes; Desiccation; Odorants; Temperature; Terpenes

The anticonvulsant activities of Crocus sativus stigma constituents, safranal and crocin, were evaluated in mice using pentylenetetrazole (PTZ)-induced convulsions in mice. Safranal (0.15 and 0.35 ml/kg, i.p.) reduced the seizure duration, delayed the onset of tonic convulsions and protected mice from death. Crocin (200 mg/kg, i.p.) did not show anticonvulsant activity.

Topics: Animals; Anticonvulsants; Carotenoids; Crocus; Cyclohexenes; Mice; Pentylenetetrazole; Seizures; Terpenes

Radical scavenging activity is involved in aging processes, antiinflammatory, anticancer and wound healing activity. Hence, in the present study the DPPH radical scavenging activity of a natural product that possesses biological properties, an extract of Crocus sativus L. (saffron), grown in Crocos, Kozani (Greece), and some of its bioactive constituents (crocin, safranal) was studied. It was shown that a methanol extract of Crocus sativus exhibited high antioxidant activity, although it contains several active and inactive constituents. In trying to approximate a structure-activity relationship, two bioactive constituents of saffron extract were tested, namely crocin and safranal. Crocin showed high radical scavenging activity (50% and 65% for 500 and 1,000 ppm solution in methanol, respectively), followed by safranal (34% for 500 ppm solution). All the tested samples showed high radical scavenging activity, probably due to the ability to donate a hydrogen atom to the DPPH radical.Thus, saffron grown in Greece can be used promisingly in functional foods, drinks with antioxidant activity, in pharmaceutical and cosmetic preparations for their antioxidant activity and probably for their antiaging activity. Saffron can also be used internally in the form of powder or other pharmacotechnical formulae as a food supplement with antioxidant properties.

Topics: Carotenoids; Crocus; Cyclohexenes; Flowers; Free Radical Scavengers; Plant Extracts; Structure-Activity Relationship; Terpenes

Extracts of saffron (Crocus sativus L.) have been reported to inhibit cell growth of human tumor cells. In order to study the cytotoxic effect of the characteristic compounds of saffron spice, we have isolated crocin, crocetin, picrocrocin and safranal. Doses inducing 50% cell growth inhibition (LD50) on HeLa cells were 2.3 mg/ml for an ethanolic extract of saffron dry stigmas, 3 mM for crocin, 0.8 mM for safranal and 3 mM for picrocrocin. Crocetin did not show cytotoxic effect. Cells treated with crocin exhibited wide cytoplasmic vacuole-like areas, reduced cytoplasm, cell shrinkage and pyknotic nuclei, suggesting apoptosis induction. Considering its water-solubility and high inhibitory growth effect, crocin is the more promising saffron compound to be assayed as a cancer therapeutic agent.

Topics: Antineoplastic Agents, Phytogenic; Carotenoids; Cell Division; Condiments; Cyclohexenes; Drug Screening Assays, Antitumor; Glucosides; HeLa Cells; Humans; Plant Extracts; Plants, Edible; Terpenes

High-performance liquid chromatography with photodiode-array detection was used to separate picrocrocin (bitter-tasting component, glucoside of safranal), cis/trans-crocins (carotenoids, glucosyl esters of crocetin) and safranal (flavour, monoterpene aldehyde) of saffron. All components of pure red Greek saffron were extracted from dried stigma with 50% methanol. These compounds were detected, separated collected and identified simultaneously using a Merck LiChroCART 125-4 Superspher 100 RP-18 (4 microns) column and as mobile phase a linear gradient from 20% to 100% acetonitrile in water in 20 min with a detection wavelength at 308 nm.

Topics: Carotenoids; Chromatography, High Pressure Liquid; Condiments; Cyclohexenes; Glucosides; Spectrophotometry, Ultraviolet; Spices; Terpenes