crocin and Alzheimer-Disease

Chronic stress and high levels of glucocorticoids produce functional and structural changes in brain and especially in the hippocampus, an important limbic system structure that plays a key role in cognitive functions including learning and memory. Alzheimer's disease (AD) is a chronic neurodegenerative disease that usually starts slowly and worsens over time. Indeed, cognitive dysfunction, neuronal atrophy, and synaptic loss are associated with both AD and chronic stress. Recent preclinical and clinical studies have highlighted a possible link between chronic stress, cognitive decline and the development of AD. It is suggested that Tau protein is an essential mediator of the neurodegenerative effects of stress and glucocorticoids towards the development of AD pathology. Recent findings from animal and humans studies demonstrated that saffron and its main constitutive crocin are effective against chronic stress-induced cognitive dysfunction and oxidative stress and slowed cognitive decline in AD. The inhibitory actions on acetylcholinesterase activity, aggregation of beta-amyloid protein into amyloid plaques and tau protein into neurofibrillary tangles, and also the antioxidant, anti-inflammatory, and the promotion of synaptic plasticity effects are among the possible mechanisms to explain the neuroprotective effects of saffron. New evidences demonstrate that saffron and its main component crocin might be a promising target for cognition improvement in AD and stress-related disorders.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents; Antioxidants; Brain; Carotenoids; Cholinesterase Inhibitors; Chronic Disease; Cognition; Crocus; Humans; Inflammation; Nootropic Agents; Oxidative Stress; Phosphorylation; Risk Factors; Stress, Psychological; tau Proteins

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

Alzheimer's disease (AD) is the most common form of dementia, in which the death of brain cells causes memory loss and cognitive decline. Several factors are thought to play roles in the development and course of AD. Existing medical therapies only modestly alleviate and delay cognitive symptoms. Current research has been focused on developing antibodies to remove the aggregates of amyloid-β (Aβ) and tau protein. This approach has achieved removal of Aβ; however, no cognitive improvement in AD patients has been reported. The biological properties of saffron, the dry stigma of the plant Crocus sativus L., and particularly its main constituent crocin, have been studied extensively for many conditions including dementia and traumatic brain injury. Crocin is a unique antioxidant because it is a water-soluble carotenoid. Crocin has shown potential to improve learning and memory as well as protect brain cells. A search of the studies on saffron and crocin that have been published in recent years for their impact on AD as well as crocin's effects on Aβ and tau protein has been conducted. This review demonstrates that crocin exhibits multifunctional protective activities in the brain and could be a promising agent applied as a supplement or drug for prevention or treatment of AD.

Topics: Alzheimer Disease; Animals; Antioxidants; Carotenoids; Cognition; Crocus; Humans; Memory; Plant Extracts

Topics: Alzheimer Disease; Carotenoids; Fruit; Nicotiana

Amyloid β-peptides (Aβ) are considered as a major hallmark of Alzheimer's disease (AD) that can induce synaptic loss and apoptosis in brain regions, particularly in the cortex and the hippocampus. Evidence suggests that crocin, as the major component of saffron, can exhibit neuromodulatory effects in AD. However, specific data related to their efficacy to attenuate the synaptic loss and neuronal death in animal models of AD are limited. Hence, we investigated the efficacy of crocin in the CA3 and dentate gyrus (DG) regions of the hippocampus and also in frontal cortex neurons employing a rat model of AD. Male Wistar rats were randomly divided into control, sham, AD model, crocin, and AD model + crocin groups, with 8 rats per group. AD model was established by injecting Aβ1-42 into the frontal cortex rats, and thereafter the rats were administrated by crocin (30 mg/kg) for a duration of 12-day. The number of live cells, neuronal arborization and apoptosis were measured using a Cresyl violet, Golgi-Cox and TUNEL staining, respectively. Results showed that, the number of live cells in the hippocampus pyramidal neurons in the CA3 and granular cells in the DG regions of the AD rats significantly decreased, which was significantly rescued by crocin. Compared with the control group, the axonal, spine and dendrites arborization in the frontal cortex and CA3 region of the AD model group significantly decreased. The crocin could significantly reverse this arborization loss in the AD rats (P < 0.05). The apoptotic cell number in the CA3 and DG regions in the AD model group was significantly higher than that of the control group (P < 0.05), while crocin significantly decreased the apoptotic cell number in the AD group (P < 0.05). Conclusion. Crocin can improve the synaptic loss and neuronal death of the AD rats possibly by reducing the neuronal apoptosis.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Apoptosis; CA3 Region, Hippocampal; Carotenoids; Dentate Gyrus; Disease Models, Animal; Frontal Lobe; Male; Pyramidal Cells; Rats; Rats, Wistar

Anxiety, hippocampus synaptic plasticity deficit, as well as pro-inflammatory cytokines, are involved in Alzheimer's disease (AD). The present study is designed to evaluate the possible therapeutic effect of crocin on anxiety-like behaviours, hippocampal synaptic plasticity and neuronal shape, as well as pro-inflammatory cytokines in the hippocampus using in vivo amyloid-beta (Aβ) models of AD. The Aβ peptide (1-42) was bilaterally injected into the frontal-cortex. Five hours after the surgery, the rats were given intraperitoneal (IP) crocin (30 mg/kg) daily up to 12 days. Elevated plus maze results showed that crocin treatment after bilateral Aβ injection significantly increased the percentage of spent time into open arms, frequency of entries, and percentage of entries into open arms as compared with the Aβ group. In the open field test, the Aβ+crocin group showed a higher percentage of spent time in the centre and frequency of entries into central zone as compare with the Aβ treated animals. Administering crocin increased the number of soma, dendrites and axonal arbores in the CA1 neurons among the rats with Aβ neurotoxicity. Cresyl violet (CV) staining showed that crocin increased the number of CV-positive cells in the CA1 region of the hippocampus compared with the Aβ group. Silver-nitrate staining indicated that crocin reduced neurofibrillary tangle formation induced by Aβ. Crocin treatment attenuated the expression of TNF-α and IL-1β mRNA in the hippocampus compared with the Aβ group. Our results suggest that crocin attenuated Aβ-induced anxiety-like behaviours and neuronal damage, and synaptic plasticity loss in hippocampal CA1 neurons may via its anti-inflammatory effects.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Carotenoids; Hippocampus; Male; Memory Disorders; Neurons; Peptide Fragments; Rats

Alzheimer's disease (AD) is a most common neurodegenerative disorder worldwide. Because of its complex pathogenesis, the prevention and therapies of AD still are a severe challenge. Evidence suggested that crocin, the major component of saffron, exhibited neuroprotective effects in AD. As such, in this study, N2a/APP695swe cells were enrolled to investigate the effects of crocin on endogenous Aβ-induced neurotoxicity. Crocin (100 and 200 μM) could ameliorate cytotoxicity according to CCK-8 assay and reduce apoptosis in line with Hoechst 33,342 staining and Annexin V-FITC/PI double staining in N2a/APP695swe cells. Reduced ROS generation and elevated MMP were found in N2a/APP695swe cells treated with crocin (100 and 200 μM). Additionally, crocin at concentrations of 100 and 200 μM inhibited the release of cytochrome and attenuated caspases-3 activity in N2a/APP695swe cells. Furthermore, succinylation, crotonylation, 2-hydroxyisobutyrylation, malonylation, and phosphorylation were significantly reduced, while a slight increase of acetylation was found in 100-μM crocin treated N2a/APP695swe cells. Taken together, crocin may be a promising natural product candidate for the effective cure of AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Apoptosis; Carotenoids; Humans; Neuroprotective Agents; Phosphorylation

To investigate the effect of crocin on the learning and memory acquisition of AD rats and its underlying mechanisms.. The learning and memory abilities of AD rats were significantly decreased, which was significantly rescued by resveratrol and crocin. The apoptotic cell number of Hippo and PFC neurons in AD model group was significantly higher than that in control group (. Crocin can improve the learning and memory ability of AD rats possibly by reducing endoplasmic reticulum stress and neuronal apoptosis.

Topics: Alzheimer Disease; Animals; Apoptosis; Apoptosis Regulatory Proteins; Behavior, Animal; CA1 Region, Hippocampal; Carotenoids; Cerebral Cortex; Cognition; Disease Models, Animal; Endoplasmic Reticulum Stress; Male; Neurons; Rats; Rats, Wistar

Due to its complex pathogenesis, the prevention and therapization of Alzheimer's disease (AD) remains a serious challenge. Crocin, the main compound isolated from Crocus sativus L., demonstrates various pharmacological activities including anti‑apoptotic properties. The present study investigated the neuroprotective effect of crocin and the underlying mechanisms. In l‑glutamate‑damaged HT22 cells, 3‑h crocin pretreatment strongly enhanced the HT22 cell viability, reduced the apoptotic rate, mitigated mitochondrial dysfunction, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells. Additionally, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase‑3 and increased the expression levels of B‑cell lymphoma‑extra large, phosphorylated (P‑) protein kinase B and P‑mammalian target of rapamycin compared with untreated cells. In mice with AD induced by d‑galactose and aluminum trichloride, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test, and reduced their escape time in the Morris water maze test compared with untreated mice. Biochemical analysis confirmed that crocin was able to reduce the Aβ1‑42 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice. Immunohistochemical analysis demonstrated that crocin reduced Aβ1‑42 deposition in the hippocampus of the brains of treated mice compared with untreated mice. In conclusion, crocin demonstrates good prospects in the treatment of AD through the oxidative stress‑associated apoptosis signaling pathway.

Topics: Alzheimer Disease; Animals; Antioxidants; Apoptosis; Calcium; Carotenoids; Cell Line; Cell Survival; Cognition; Disease Models, Animal; Glutamic Acid; Mice; Mitochondria; Neuroprotective Agents; Oxidative Stress; Pyramidal Cells; Reactive Oxygen Species

Intracerebroventricular (ICV) streptozotocin (STZ) has been shown to cause cognitive impairment, associated with free radical generation. In this study, we evaluated the effects of crocin on cognitive performance in ICV STZ-lesioned rats (3 mg/kg bilaterally, on day 1 and 3). Crocin (100 mg/kg, p.o.) was administered for 21 consecutive days, starting 1h prior to the first dose of STZ. Cognitive performance was assessed using Morris water maze task while the parameters of oxidative stress assessed, were malondialdehyde (MDA) and total thiol levels besides glutathione peroxidase (GPx) activity. STZ-lesioned rats showed a severe deficit in memory associated with elevated MDA levels, reduced GPx activity and total thiol content. Crocin treatment improved cognitive performance and resulted in a significant reduction in MDA levels and elevation in total thiol content and GPx activity. This study demonstrates that crocin may have beneficial effects in the treatment of neurodegenerative disorders such as Alzheimer's disease.

Topics: Alzheimer Disease; Animals; Antioxidants; Brain; Carotenoids; Cognition; Cognition Disorders; Crocus; Free Radicals; Glutathione Peroxidase; Male; Malondialdehyde; Maze Learning; Memory Disorders; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Streptozocin; Sulfhydryl Compounds