crocin and Cognition-Disorders

This study investigated whether crocin exerted neuroprotective effects against acute hypobaric hypoxia at high altitude in vivo and determined the underlying mechanisms. Male Sprague-Dawley rats were randomly assigned to a normoxic group，a hypoxic group, and three crocin groups at three different doses. The rats were transferred from 50m to 4200m for 3 days after treatment with crocin for 3 days. The learning and memory of the rat were evaluated with the Morris water maze test. Transmission electron microscope (TEM) was used to analyze the changes in the ultrastructure of hippocampal neurons. Peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) and sirtuin-1 (SIRT1) levels were determined using immunohistochemical staining and western blotting. The escape latency of the crocin group was shorter than that of the hypoxic group, while the frequency of the rats reaching the platform was significantly higher in the crocin group. The structures of nerve cells and mitochondria were destroyed in the hypoxic group, but were repaired in the crocin groups. The expressions of PGC-1α and SIRT1 were decreased in the hypoxic group, but were increased in the crocin group. All the effects improved by crocin were dose-dependent. Crocin attenuates acute hypobaric hypoxia-induced cognitive deficits in rats, accompanied by repairing the structures of hippocampal neurons and improving PGC-1α and SIRT1 levels.

Topics: Acute Disease; Animals; Carotenoids; Cognition Disorders; Gene Expression Regulation; Hippocampus; Hypoxia; Male; Maze Learning; Neurons; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Protein Transport; Rats; Rats, Sprague-Dawley; Sirtuin 1

Crocin is a pharmacologically active carotenoid pigment mainly present in the stigmas of Crocus sativus L. (Iridaceae). It has been well explored in experimental animal models of cognitive impairments, depression, anxiety and epilepsy. This study was designed to understand the effect of crocin on pentylenetetrazol (PTZ)-induced kindling development and its associated cognitive deficit in mouse. Crocin treatment at 5, 10 and 20 mg/kg p.o. doses showed a marked reduction in severity of PTZ-induced seizures. There was an increase in novel object preference index and discrimination ratio in the crocin-treated groups in the novel object recognition test. Its treatment also increased percentage spontaneous alternations in T-maze test at all the tested doses. Histopathological examination by Nissl staining showed a reduction in dark neurons in the hippocampal pyramidal layer of crocin-treated animals in contrast to vehicle control, indicating a decrease in neuronal damage. Biochemical estimations showed a significant increase in superoxide dismutase activity and reduced reactive oxygen species (ROS) in the hippocampus of crocin-treated animals. Immunohistochemistry results revealed attenuation in the levels of nuclear factor-κB (NF-κB) and phosphorylated NF-κB in the hippocampal sections of crocin-treated animals. The results of this study concluded that crocin treatment increased seizure threshold, thus inhibiting PTZ-induced kindling development and improving cognitive functions. The effect was found to be due to suppression of seizure-induced ROS generation and its linked NF-κB pathway-associated neuronal damage.

Topics: Animals; Carotenoids; Cognition Disorders; Cognitive Dysfunction; Crocus; Disease Models, Animal; Dose-Response Relationship, Drug; Hippocampus; Kindling, Neurologic; Male; Maze Learning; Mice; Neurons; NF-kappa B; Pentylenetetrazole; Reactive Oxygen Species; Seizures; Severity of Illness Index; Superoxide Dismutase

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