Effects of Spices (Saffron, Rosemary, Cinnamon, Turmeric and Ginger) in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent dementia in the elderly, causing disability, physical, psychological, social, and economic damage to the individual, their families, and caregivers. Studies have shown some spices, such as saffron, rosemary, cinnamon, turmeric, and ginger, have antioxidant and anti-inflammatory properties that act in inhibiting the aggregation of acetylcholinesterase and amyloid in AD. For this reason, spices have been studied as beneficial sources against neurodegenerative diseases, including AD. In this sense, this study aims to present a review of some spices (Saffron, Rosemary, Cinnamon, Turmeric and Ginger) and their bioactive compounds, most consumed and investigated in the world regarding AD. In this article, scientific evidence is compiled in clinical trials in adults, the elderly, animals, and in vitro, on properties considered neuroprotective, having no or negative effects on neuroprotection of these spices and their bioactive compounds. The importance of this issue is based on the pharmacological treatment for AD that is still not very effective. In addition, the recommendations and prescriptions of these spices are still permeated by questioning and lack of robust evidence of their effects on neurodegeneration. The literature search suggests all spices included in this article have bioactive compounds with anti-inflammatory and antioxidant actions associated with neuroprotection. To date, the amounts of spice ingestion in humans are not uniform, and there is no consensus on its indication and chronic consumption guarantees safety and efficacy in neuroprotection. Therefore, clinical evidence on this topic is necessary to become a formal adjuvant treatment for AD.

The effect of salt stress on the production of apocarotenoids and the expression of genes related to their biosynthesis in saffron.

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-ß 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+ and decreased uptake of K+ in salt treated compared to control plants indicating an effective salt stress. HPLC analysis of apocarotenoids revealed that crocin production was significantly halted (P < 0.05) with increasing salt concentration while picrocrocin level did not change with moderate salt but significantly dropped by high salt concentration. Real-time PCR analysis revealed a progressive decrease in transcript levels of CsUGT2 and CsLCYB genes with increasing salt concentration (P < 0.05). The expression of CsCCD2 and CsCHY-ß tolerated moderate salt concentration but significantly downregulated with high salt concentration. CsCCD4 however responded differently to salt concentration being decreased with moderate salt but increased at higher salt concentration. Our result suggested that salt stress had an adverse effect on the production of saffron apocarotenoids and it is likely influencing the quality of saffron stigma produced.

The effect of novel simple saffron syrup on fatigue reduction in patients with multiple sclerosis.

Objectives Multiple sclerosis (MS) is a progressive and often debilitating neurological disorder. This chronic disease has a high prevalence in the world and also in Iran. Fatigue is a common symptom of the disease, which causes serious mental and psychological discomfort. Simple saffron syrup, contains some compounds that can be effective in relieving the symptom. The object of this study is to investigate the effect of simple saffron syrup on fatigue in patients with MS. Methods This study is a pre-post study which evaluates the fatigue rate of MS patients (30 participants) according to the FSS scale. The participants were given a saffron simple syrup to consume a tablespoon (7.5 cc) every 8 h for two months. After 60 days of prescribing, patients are assessed for fatigue based on fatigue severity scale (FSS) criteria. Results One-way ANOVA showed that there was a notable difference between the mean score of fatigue in MS patients before and after the intervention (p<0.001). So, the fatigue severity of the subjects after saffron syrup consumption dropped dramatically for two months. (p<00.01). Conclusions According to the outcomes of this study, simple saffron syrup can be effective as an adjunct therapy for fatigue reduction in patients with MS due to effectiveness besides no significant side effects.

Crocus sativus L. Versus Methylphenidate in Treatment of Children with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Pilot Study.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders of childhood and adolescence. About 30% of patients do not respond to stimulants or cannot tolerate their side effects. Thus, alternative medication, like herbal medicine, should be considered. The aim of this trial is to compare the safety and efficacy of Crocus sativus (saffron) versus methylphenidate in improving symptoms of children with ADHD. METHODS: In a 6-week randomized double-blind study, 54 patients (children 6-17 years old) with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of ADHD were randomly assigned to receive either 20-30 mg/d (20 mg/d for <30 kg and 30 mg/d for >30 kg) methylphenidate (MPH) or 20-30 mg/d saffron capsules depending on weight (20 mg/d for <30 kg and 30 mg/d for >30 kg). Symptoms were assessed using the Teacher and Parent Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) at baseline and weeks 3 and 6. RESULTS: Fifty patients completed the trial. General linear model repeated measures showed no significant difference between the two groups on Parent and Teacher Rating Scale scores (F = 0.749, df = 1.317, p = 0.425, and F = 0.249, df = 1.410, p = 0.701, respectively). Changes in Teacher and Parent ADHD Rating Scale scores from baseline to the study end were not significantly different between the saffron group and the MPH group (p = 0.731 and p = 0.883, respectively). The frequency of adverse effects was similar between saffron and MPH groups. CONCLUSION: Short-term therapy with saffron capsule showed the same efficacy compared with methylphenidate. Nevertheless, larger controlled studies with longer treatment periods are necessary for future studies.

Neuroprotective effect of safranal, an active ingredient of Crocus sativus , in a rat model of transient cerebral ischemia.

Safranal is a monoterpene aldehyde found in saffron (Crocus sativus L.) petals. It has been previously reported that safranal has a wide range of activities such as antioxidant and anti-inflammatory effects. In this study, we examined the effect of safranal on brain injuries in a transient model of focal cerebral ischemia. Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 30 min, followed by 24 h of reperfusion. Safranal in the doses of 72.5 and 145 mg/kg was administered intraperitoneally at 0, 3, and 6 h after reperfusion. Neurobehavioral deficit, infarct volume, hippocampal cell loss and markers of oxidative stress including thiobarbituric acid reactive substances (TBARS), total sulfhydryl (SH) content, and antioxidant capacity (using FRAP assay) were also assessed. The focal cerebral ischemia induced a significant increase in the neurological score, infarct volume and neuronal cell loss in the ipsilateral hippocampal CA1 and CA3 subfields (p < 0.001) and also oxidative stress markers (p < 0.01). Following safranal administration, the total SH content and antioxidant capacity significantly increased, while marked decreases were observed in the neurological score, infarct volume and hippocampal cell loss, as well as TBARS level. This study concluded that safranal had protective effects on ischemic reperfusion injury in the rat model of stroke. Such effects of safranal may have been exerted mainly by suppressing the production of free radicals and increasing antioxidant activity.

Apical dominance in saffron and the involvement of the branching enzymes CCD7 and CCD8 in the control of bud sprouting.

BACKGROUND: In saffron (Crocus sativus), new corms develop at the base of every shoot developed from the maternal corm, a globular underground storage stem. Since the degree of bud sprouts influences the number and size of new corms, and strigolactones (SLs) suppress growth of pre-formed axillary bud, it was considered appropriate to investigate SL involvement in physiology and molecular biology in saffron. We focused on two of the genes within the SL pathway, CCD7 and CCD8, encoding carotenoid cleavage enzymes required for the production of SLs. RESULTS: The CsCCD7 and CsCCD8 genes are the first ones isolated and characterized from a non-grass monocotyledonous plant. CsCCD7 and CsCCD8 expression showed some overlapping, although they were not identical. CsCCD8 was highly expressed in quiescent axillary buds and decapitation dramatically reduced its expression levels, suggesting its involvement in the suppression of axillary bud outgrowth. Furthermore, in vitro experiments showed also the involvement of auxin, cytokinin and jasmonic acid on the sprouting of axillary buds from corms in which the apical bud was removed. In addition, CsCCD8 expression, but not CsCCD7, was higher in the newly developed vascular tissue of axillary buds compared to the vascular tissue of the apical bud. CONCLUSIONS: We showed that production and transport of auxin in saffron corms could act synergistically with SLs to arrest the outgrowth of the axillary buds, similar to the control of above-ground shoot branching. In addition, jasmonic acid seems to play a prominent role in bud dormancy in saffron. While cytokinins from roots promote bud outgrowth. In addition the expression results of CsCCD8 suggest that SLs could positively regulate procambial activity and the development of new vascular tissues connecting leaves with the mother corm.

In vitro cormlet production of saffron (Crocus sativus L. Kashmirianus) and their flowering response under greenhouse.

A complete protocol for the saffron cormlet production under in vitro conditions and subsequent flowering under greenhouse conditions is described. Highest number of cormlets (70.0 ± 0.30) per corm slice (explant) could be regenerated on Murashige and Skoog (MS) half strength medium supplemented with thidiazuron (TDZ) (20 µM), Indole acetic acid (IAA) (10 µM), and sucrose (40 g/l). Maximum germination (90%) of these cormlets could be achieved on MS medium containing 6-benzyl amino purine (BAP) (20 µM) and α-naphthalene acetic acid (NAA) (15 µM). In order to increase the size of the in vitro raised cormlets, these were cultured on MS medium containing TDZ (15 µM) and IAA in the range of 1.5-30 µM. Maximum increase in cormlet size could be attained on TDZ (15 µM) + IAA (12.5 µM) + sucrose (30 g/l), and the average size of cormlets was 2.5g. In another experiment, apical vegetative buds of actively growing corms were cultured for cormlet development, and corms of size 2.5g could be developed on MS medium with NAA (15 µM), BAP (20 µM), and sucrose (30 g/l). The in vitro developed cormlets were dried under shade at 25 ± 2°C for 7 d. These were then planted in small cups containing clay loam soil and kept in green house at 20 ± 2°C. In vitro developed cormlets with mean weight 2.5 g showed maximum flowering (25%) as well as vegetative growth (55%), while only 19% cormlets of 2.0 g flowered. To our knowledge this is the first report on successful flowering from in vitro raised cormlets under greenhouse.

Hormone and microorganism treatments in the cultivation of saffron (Crocus sativus L.) plants.

The difficult cultivation of the saffron plant (Crocus Sativus L.) make the spice of the same name made from its dried stigmas very valuable. It is estimated that some 75,000 blossoms or 225,000 hand-picked stigmas are required to make a single pound of saffron, which explains why it is the world's most expensive spice. The aim of this study was to identify ways of increasing the fertility and production of saffron. For this purpose, the treatment of saffron bulbs with a synthetic growth hormone--a mixture of Polystimulins A6 and K--and two different microorganism based materials--biohumus or vermicompost and Effective Microorganisms (EM)--in four different ways (hormone alone, biohumus alone, EM alone and EM+biohumus) was investigated to determine whether these treatments have any statistically meaningful effects on corms and stigmas. It has been shown that EM + biohumus was the most effective choice for improved saffron cultivation.

Effects of different hormonal treatments on the callus production and plantlet regeneration in saffron (Crocus sativus L.).

Saffron (Crocus sativus L.) is one of valuable and native plants in the land of Iran. By this investigation the best hormonal compositions for callus production from protoplast and for plantlet regeneration from callus were determined. To isolate protoplasts, the embryogenic calli were used. The embryogenic calli were immersed in enzymatic solution to degrade the cell walls. The treated mixture was filtered and then centrifuged at 100 g for 3-5 min and the resulted pellet was rinsed. After one step of washing and another step of centrifugation, the protoplasts were gently mixed with sterile sodium alginate solution and added to MS broth consisting 1% calcium chloride and 0.3 M manitol to form calcium alginates granules. The protoplast-containing granules were exposed to MS broth including 0.3 M manitol and various treatments of two kinds of auxins (2, 4-D and NAA) and three kinds of cytokinins (2ip, Kin, BAP), respectively in four rates of 0.1, 0.2, 0.5, 1.0 mg L(-1) for auxins and in three rates of 0.1, 0.2 and 0.5 mg L(-1) for cytokinins, incubated in dark at 22 +/- 2 degrees C for a period of 30 days. Out of all the treatment of 2, 4-D (1.0 mg L(-1)) and Kin (0.2 mg L(-1)) was the best in callus induction. In order to regenerate plantlets, the resulted calli were transferred to MS broth amended with different rates of ABA (0.0, 0.5, 1.0, 1.5, 2.0 and 2.5 mg L(-1)) so that they could pass the steps of embryonic maturation. The mature embryos were transferred to MS media with different rates of GA3 (0.0, 5.0, 15.0, 20.0, 25.0 and 30.04 mg L(-1)) to initiate germination. The germinated embryos were then placed in solid MS media with various rates of NAA and 2, 4-D auxins (0.0, 0.5, 1.0 and 2.0 mg L(-1)) and different levels of BAP and Kin cytokinins (0.0, 0.5, 1.0 mg L(-1)). Results from statistical analyses indicated the treatment of NAA and BAP (each 1 mg L(-1)) as the best hormonal treatment for the plantlet regeneration from the domestic saffron calli.

Effects of different concentrations of 2,4-D and BAP on somatic embryogenesis induction in saffron (Crocus sativus L.).

To optimize an in vitro protocol for propagation of saffron through somatic embryogenesis, effects of various concentrations of 2,4-D ( 0, 0.25, 0.5, 1, 2, 4 and 8 mg L(-1)) in combination with BAP (0, 0.25, 0.5, 1, 2, 4 and 8 mg L(-1)) were studied. Surface-sterilized corms were cut transversally into equal portions and the upper or lower parts were used separately as explants. All treatments were maintained in the darkness at 24 +/- 2 degrees C. After 70 days, the first globular embryos were observed and the number of embryos on each explant reached to its maximum 3 months after culture. Statistical analysis showed that there were significant differences between treatments regarding the number of embryos induced on each explant. The most effective treatment was 2.0 mg L(-1) 2,4-D + 1.0 mg L(-1) BAP for both types of explant (inducing 6.5 +/- 1.3 and 35.95 +/- 4.9 embryos on each explant for the upper and lower parts, respectively). The average percentages of explants showing embryogenic response were 33.3 and 93.3% for the upper and the lower part of corm tissue respectively in this treatment. Complementary studies are in progress to optimize maturation and germination stages of these somatic embryos.

Induction of somatic embryogenesis in saffron using thidiazuron (TDZ).

In vitro propagation of saffron either through somatic embryogenesis or cormogenesis is considered to be an efficient alternative method for large-scale propagation of pathogen-free corms. In order to develop an efficient protocol for in vitro propagation of saffron, a factorial experiment was carried out based on completely randomized design to investigate the effects of various concentrations of TDZ (0, 0.1, 0.25 and 0.5 mg L(-1)) on somatic embryogenesis induction from 5 different types of corm explants (terminal or axillary buds, upper or lower parts of the corm tissue and terminal buds from pre-treated corms at 4 degrees C for 2 weeks). The results revealed that TDZ concentrations affected the induction of somatic embryogenesis significantly while different types of corm explants showed no significant effect on this process. Among TDZ concentrations used, 0.5 mg L(-1) was the most effective treatment for embryogenesis induction. Embryogenic calli (globular stage) proliferated well when subcultured into MS medium supplemented with 0.25 mg L(-1) TDZ before transferring to hormone-free MS medium containing 6% sucrose for maturation (scutellar or horn-shape stage). Matured embryos were transferred to half strength MS medium without growth regulators for further development, from which microcorms were produced at the basal part after 3 months.

Fusaric acid induces apoptosis in saffron root-tip cells: roles of caspase-like activity, cytochrome c, and H2O2.

Programmed cell death (PCD), now known as apoptosis, is accompanied by specific morphological features. In this study, fusaric acid, a fusarium mycotoxin, was used to examine cell death in saffron (Crocus sativus Linnaeus) roots, using several apoptosis assays. Our results show that moderate FA doses (50-100 microM) induce apoptotic features while high FA doses (> 200 microM) stimulate necrosis. The apoptotic-like features induced by moderate doses of FA include chromatin condensation, formation of condensed chromatin spheres which bud from the nucleus, fragmentation of nucleosomal DNA into approximately 180 bp fragments, exposure of phosphatidyl serine to the external membrane leaflet, delivery of cytochrome c to cytosol, and generation of H(2)O(2). These apoptotic alterations in root cells are not observed in the presence of serine protease, caspase-1 or caspase-3 inhibitors. It is proposed that production of H(2)O(2) and release of cytochrome c into the cytosol may activate caspase-like proteases and thus establish the apoptotic pathway. As nuclei budding spheres formed in plant root cells after exposure to 50-100 microM FA doses seem to be digested inside the cytosol, we suggest labeling them as internal apoptotic bodies (IAB) that may be more informative than previously used term, apoptotic-like bodies.

[Physiological and ecological effects of potassium on expansion of crocus corm].

The corm size of Crocus sativus, a well-known medicine, is a key limiting factor for its stigma harvest. A water cultural experiment with four different potassium (K) concentrations showed that the K content, chlorophyll content, relative ATP content and net photosynthetic rate in C. sativus leaves increased with improving K concentration, which enhanced the function of leaves to be metabolic source. On the other hand, the K absorbing ability and the contents of soluble sugars, vitamin C (Vc) and protein in new-born corms were increased with improving K concentration, which also strengthened the function of new-born corms to be metabolic sink. This study also showed that K could promote the new-born corm growth rate of C. sativus through strengthening the function of "source" and "sink".

Production of crocin using Crocus sativus callus by two-stage culture system.

Saffron callus was grown in a two-stage culture on B5 medium supplemented with casein hydrolysate (300 mg l(-1)) at 22 degrees C in dark with naphthalene acetic acid (2 mg l(-1)) and 6-benzyladenine (1 mg l(-1)) to give maximum biomass (16 g dry wt l(-1)), and with indole 3-acetic acid (2 mg l(-1)) and 6-benzyladenine (0.5 mg l(-1)) for crocin formation. The maximum crocin production (0.43 g l(-1)) was achieved by this two-stage culture method, which was three times that by a one-stage method.