The gabaa-benzodiazepine receptor antagonist flumazenil abolishes the anxiolytic effects of the active constituents of crocus sativus l. Crocins in rats

Anxiety is a chronic severe psychiatric disorder. Crocins are among the various bioactive components of the plant Crocus sativus L. (Iridaceae) and their implication in anxiety is well-documented. However, which is the mechanism of action underlying the anti-anxiety effects of crocins remains unknown. In this context, it has been suggested that these beneficial effects might be ascribed to the agonistic properties of these bioactive ingredients of saffron on the GABA type A receptor. The current experimentation was undertaken to clarify this issue in the rat. For this research project, the light/dark and the open field tests were used. A single injection of crocins (50 mg/kg, i.p., 60 min before testing) induces an anti-anxiety-like effect revealed either in the light-dark or open field tests. Acute administration of the GABAA-benzodiazepine receptor antagonist flumazenil (10 mg/kg, i.p., 30 min before testing) abolished the above mentioned anxiolytic effects of crocins. The current findings suggest a functional interaction between crocins and the GABAA receptor allosteric modulator flumazenil on anxiety. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Crocins, the bioactive components of crocus sativus l., counteract the disrupting effects of anesthetic ketamine on memory in rats

Consistent experimental evidence suggests that anesthetic doses of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine cause severe memory impairments in rodents. Crocins are among the various bioactive ingredients of the plant Crocus sativus L., and their implication in memory is well-documented. It has not yet been elucidated if crocins are able to attenuate the memory deficits produced by anesthetic ketamine. The present study was undertaken aiming to clarify this issue in the rat. For this aim, the object recognition, the object location and the habituation tests, reflecting non-spatial recognition memory, spatial recognition memory and associative memory, respectively, were utilized. A post-training challenge with crocins (15–30 mg/kg, intraperitoneally (i.p.), acutely) counteracted anesthetic ketamine (100 mg/kg, i.p.)-induced performance impairments in all the above-mentioned behavioral memory paradigms. The current findings suggest that crocins modulate anesthetic ketamine’s amnestic effects. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Crocins, the active constituents of Crocus sativus L., counteracted apomorphine-induced performance deficits in the novel object recognition task, but not novel object location task, in rats

Schizophrenia is a chronic mental disease that affects nearly 1% of the population worldwide. Several lines of evidence suggest that the dopaminergic (DAergic) system might be compromised in schizophrenia. Specifically, the mixed dopamine (DA) D1/D2 receptor agonist apomorphine induces schizophrenia-like symptoms in rodents, including disruption of memory abilities. Crocins are among the active components of saffron (dried stigmas of Crocus sativus L. plant) and their implication in cognition is well documented. The present study investigated whether crocins counteract non-spatial and spatial recognition memory deficits induced by apomorphine in rats. For this purpose, the novel object recognition task (NORT) and the novel object location task (NOLT) were used. The effects of compounds on mobility in a locomotor activity chamber were also investigated in rats. Post-training peripheral administration of crocins (15 and 30 mg/kg) counteracted apomorphine (1 mg/kg)-induced performance deficits in the NORT. Conversely, crocins did not attenuate spatial recognition memory deficits produced by apomorphine in the NOLT. The present data show that crocins reversed non-spatial recognition memory impairments produced by dysfunction of the DAergic system and modulate different aspects of memory components (storage and/or retrieval). The effects of compounds on recognition memory cannot be attributed to changes in locomotor activity. Further, our findings illustrate a functional interaction between crocins and the DAergic system that may be of relevance for schizophrenia-like behavioral deficits. Therefore, the utilization of crocins as an adjunctive agent, for the treatment of cognitive deficits observed in schizophrenic patients should be further investigated. © 2017 Elsevier B.V

Effects of the active constituents of Crocus sativus L. crocins and their combination with memantine on recognition memory in rats

Crocus sativus L., is a plant cultivated in many countries of the world. Crocins are among the active constituents of C. sativus and their implication in cognition has been proposed. The present study was designed to investigate in the rat the effects of crocins on distinct recognition memory components (encoding, storage and retrieval). Subsequently, the potential use of crocins as adjunctive agents for the treatment of memory disorders was examined. Thus, the effects exerted by a combination of subthreshold doses of crocins and memantine on recognition memory were evaluated. To assess the effects of compounds on memory, the novel object-recognition task (NORT) was used. In a preliminary study, the influence of the retention time (the delay between the two trials) on the performance of rats was assessed. Ratsrecognition memory abilities remained intact up to 6 h, but were extinguished when a delay of 24 h was utilized. Crocins, at any dose tested (5, 15, and 30 mg/kg), did not affect rats-performance, whereas administration of higher doses (15 and 30 mg/kg) reversed delay-dependent deficits in the NORT. The combination of subthreshold doses of crocins (5 mg/kg) and memantine (3 mg/kg) did not influence the performance, but counteracted delay-dependent deficits in the NORT. These findings suggest that crocins counteract natural forgetting and may modulate different aspects of recognition memory, and that the combined use of crocins and memantine might represent a novel strategy to treat memory disorders. © 2018 Wolters Kluwer Health, Inc. All rights reserved

Antioxidant properties of crocus Sativus L. and its constituents and relevance to neurodegenerative diseases; Focus on Alzheimer’s and Parkinson’s Disease

Background: Reactive oxygen species and reactive nitrogen species, which are collectively called reactive oxygen-nitrogen species, are the inevitable by-products of cellular metabolic redox reactions, such as oxidative phosphorylation in the mitochondrial respiratory chain, phagocytosis, reactions of biotransformation of exogenous and endogenous substrata in endoplasmic reticulum, eicosanoid synthesis, and redox reactions in the presence of metal with variable valence. Among medicinal plants, there is growing interest in Crocus Sativus L. It is a perennial, stemless herb, belonging to Iridaceae family, cultivated in various countries such as Greece, Italy, Spain, Israel, Morocco, Turkey, Iran, India, China, Egypt and Mexico. Objective: The present study aims to address the protective role of Crocus Sativus L. in neurodegeneration with an emphasis in Parkinson’s and Alzheimer’s disease. Materials and Methods: An electronic literature search was conducted by two of the authors from 1993 to August 2017. Original articles and systematic reviews (with or without meta-analysis), as well as case reports were selected. Titles and abstracts of papers were screened by a third reviewer to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved. Results: Hence, the authors focused on the literature concerning the role of Crocus Sativus L. on its anti-oxidant and neuroprotective properties. Conclusion: Literature findings represented in current review herald promising results for using Crocus Sativus L. and/or its active constituents as antioxidants, anti-inflammatory, and neuroprotective agents. © 2019 Bentham Science Publishers

Tumor-suppressing properties of crocus sativus L.: Nature as an anti-cancer agent

Cancer is a growing problem because it is a chronic disease that affects, not only patient health, but also its daily living. Concurrent cancer therapies have ameliorated cancer prevalence, but the severity and frequency of toxicity and side effects during therapy have led the scientific community to rediscover the possible therapeutic effectiveness of herbs and spices. Crocus sativus L., commonly known as saffron, has been used in folk medicine for centuries. Today, data from numerous in vivo and in vitro studies support its anti-cancer activity, making it a promising anti-cancer agent for study. In the present review, we focus on the anti-cancer activity of C. sativus and its derivates. Medications that are currently used as chemotherapeutic or anti-cancer agents are associated with side effects whether used at effective doses or at levels that exceed the therapeutic dose. Therefore, many cancer survivors suffer from serious and even life-threatening long-or short-term sequelae, so the development of alternative/coadjutant drugs is imperative. © 2017 by Begell House, Inc

Incidence of bacteriocins produced by food-related lactic acid bacteria active towards oral pathogens

In the present study we investigated the incidence of bacteriocins produced by 236 lactic acid bacteria (LAB) food isolates against pathogenic or opportunistic pathogenic oral bacteria. This set of LAB contained several strains (≥17%) producing bacteriocins active against food-related bacteria. Interestingly only Streptococcus macedonicus ACA-DC 198 was able to inhibit the growth of Streptococcus oralis, Streptococcus sanguinis and Streptococcus gordonii, while Lactobacillus fermentum ACA-DC 179 and Lactobacillus plantarun ACA-DC 269 produced bacteriocins solely against Streptococcus oralis. Thus, the percentage of strains that were found to produce bacteriocins against oral bacteria was ~1.3%. The rarity of bacteriocins active against oral LAB pathogens produced by food-related LAB was unexpected given their close phylogenetic relationship. Nevertheless, when tested in inhibition assays, the potency of the bacteriocin(s) of S. macedonicus ACA-DC 198 against the three oral streptococci was high. Fourier-transform infrared spectroscopy combined with principal component analysis revealed that exposure of the target cells to the antimicrobial compounds caused major alterations of key cellular constituents. Our findings indicate that bacteriocins produced by food-related LAB against oral LAB may be rare, but deserve further investigation since, when discovered, they can be effective antimicrobials. © 2013 by the authors; licensee MDPI, Basel, Switzerland

RNA arbitrarily primed PCR and fourier transform infrared spectroscopy reveal plasticity in the acid tolerance response of Streptococcus macedonicus

We have previously reported that an acid tolerance response (ATR) can be induced in Streptococcus macedonicus cells at mid-log phase after autoacidification, transient exposure to acidic pH, or acid habituation, as well as at stationary phase. Here, we compared the transcriptional profiles of these epigenetic phenotypes, by RNA arbitrarily primed PCR (RAP-PCR), and their whole-cell chemical compositions, by Fourier transform infrared spectroscopy (FT-IR). RAP-PCR fingerprints revealed significant differences among the phenotypes, indicating that gene expression during the ATR is influenced not only by the growth phase but also by the treatments employed to induce the response. The genes coding for the mannose-specific IID component, the 1,2-diacylglycerol 3-glucosyltransferase, the 3-oxoacyl-acyl carrier protein, the large subunit of carbamoylphosphate synthase, and a hypothetical protein were found to be induced at least under some of the acid-adapting conditions. Furthermore, principal component analysis of the second-derivative-transformed FT-IR spectra segregated S. macedonicus phenotypes individually in all spectral regions that are characteristic for major cellular constituents like the polysaccharides of the cell wall, fatty acids of the cell membrane, proteins, and other compounds that absorb in these regions. These findings provide evidence for major changes in cellular composition due to acid adaptation that were clearly different to some extent among the phenotypes. Overall, our data demonstrate the plasticity in the ATR of S. macedonicus, which reflects the inherent ability of the bacterium to adjust the response to the distinctiveness of the imposed stress condition, probably to maximize its adaptability. Copyright © 2008, American Society for Microbiology. All Rights Reserved

Crocins: The active constituents of crocus sativus l. stigmas, exert significant cytotoxicity on tumor cells in vitro

Background: Tumors of the childhood are considered to be grave and devastating pa-thologies, with high mortality rates. Current therapeutic options like cytotoxic drugs and radiotherapy target both healthy and malignant cells, thus resulting in long-term neurological and intellectual sequelae and endocrinological disorders. Objectives: In this study, we focused on the anticancer potency of crocins, the main constituents of Crocus sativus L, stigmas. Crocins were first extracted using organic solvents from the dried stigmas and then were identified using the HPLC analysis. Materials and Methods: TE-671 cells were treated with the extract of crocins using a range of concentrations between 0.25-mg/ mL and 16 mg/mL. Viability of the cells was measured at 24h, 48h, 72h and 96h. In addition, we have examined the expression levels of the p53 gene using Real-Time Reverse Transcription PCR. Results: Results showed that crocins exerted significant cytotoxic and anti-proliferative effects in a concentration and time-dependent-manner on TE-671 cells. Furthermore, p53 manifested similar expression pattern as the anti-proliferative effect of crocin. Conclusion: Our data demonstrate that crocins could be a novel promising agent for the improvement of tumor treatment. © 2019 Bentham Science Publishers

Saffron, an alternative crop for sustainable agricultural systems. A review

Saffron (Crocus sativus L.) is an autumnal flowering geophite whose dried stigmas, well known for their aromatic and colouring power, have been used since immemorial time as a spice in human nutrition, for medicinal purposes and as a dye. Many doubts remain on its origin; it was probably selected and domesticated in Crete during the Late Bronze Age. Saffron is an autotriploid geophyte species, self- and out-sterile and mostly male-sterile and therefore unable to produce seed, that reproduces by means of corms. Furthermore, it has a reverse biological cycle compared with the majority of cultivated and spontaneous plants: flowering first in October-November, then vegetative development until May, which means that the vegetative development is not directly important for production of stigmas, but for the production of new corms. Due to its unique biological, physiological and agronomic traits, saffron is able to exploit marginal land and to be included in low-input cropping systems, representing an alternative viable crop for sustainable agriculture. Notwithstanding this great potential and the considerable increase in new generation consumer demand for saffron, the future of the plant is still uncertain. Indeed, the main obstacles to saffron production are: (1) the limited areas of cultivation in countries where it is traditionally grown, (2) the great amount of sophisticated spice, (3) management techniques executed by hand, and (4) the very high price of the spice. Here we review the main biological, genetic and ecological traits associated with agronomic management techniques of saffron in relation to environmental conditions. Colour, taste and aroma are the essential features on which the quality of saffron stigmas is founded. In turn, these aspects are strictly connected with the biomolecular composition of the stigmas, namely, the carotenoids and their derivatives. With this in mind, the biosynthetic pathway that leads to the formation of saffron secondary metabolites and their abundance in the spice is presented, together with the biomedical properties commonly associated with saffron. Furthermore, a detailed overview of the more recent instrumental methods to assess the quality of saffron, strictly from a chemical point of view, will be discussed