Reversal effects of crocin on amyloid β-induced memory deficit: Modification of autophagy or apoptosis markers.
Crocin, as a carotenoid, is one of the main and active constituents of saffron stigmas (Crocus sativus L.) that is widely used in folk medicine. Several studies have pointed out the potent antioxidant and neuroprotective properties of crocin which may have therapeutic values for management of neurodegenerative disorders such as Alzheimer's disease. Alzheimer's disease is the most common form of dementia among the elderly and is characterized by massive neuronal loss and progressive cognitive impairment. Beta amyloid hypothesis is the main theoretical research framework for Alzheimer's disease which states that extracellular aggregation of beta amyloid results in synaptic loss and eventually cell apoptosis. Recent findings suggest that autophagy and apoptosis are extensively involved in Alzheimer's disease. In order to investigate therapeutic values of crocin, we examined the effect of crocin on memory, cell apoptosis, and autophagy using in vivo models of Alzheimer's disease. We also compared the effect of crocin administration on spatial memory with nicotine as positive control. Morris water maze results show that intra-peritoneal and intra-hippocampal administration of crocin significantly improve spatial memory indicators such as escape latency, traveled distance and time spent in target quadrant when compared to beta amyloid injection. Furthermore, we measured certain biomarkers of cell autophagy and apoptosis using Western blot analysis. Our results reveal that crocin administration does not cause any significant alteration in Beclin-1 and ratio of LC3-II/LC3-I compared to the group received beta amyloid by hippocampal injection. However, in contrast to autophagy, crocin administration significantly decreases Bax/Bcl-2 ratio and cleaved Caspase-3 level. This demonstrates that crocin inhibits beta amyloid induced apoptosis, which is possibly associated with its antioxidant properties. Our results further confirm the neuroprotective properties of crocin as a potential pharmaceutical agent for management of Alzheimer's disease.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Farideh
F
Asadi
Food and Drug Laboratories Research Center, Food and Drug Organization, MOH & ME, Tehran, Iran.
Amir Hossein
AH
Jamshidi
Neuroscience Research Center, Shahid Beheshti, University of Medical Sciences, Tehran, Iran.
Fariba
F
Khodagholi
Neuroscience Research Center, Shahid Beheshti, University of Medical Sciences, Tehran, Iran.
Asal
A
Yans
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Neuroscience Department, School of Advanced Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Leila
L
Azimi
Shaheed Beheshti University of Medical Sciences, Faculty of Pharmacy & Pharmaceutical Science Research Center, Department of Pharmacology, Tehran, Iran.
Mehrdad
M
Faizi
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, Sulaibekhat, Kuwait.
Leila
L
Vali
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad
M
Abdollahi
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad Hossein
MH
Ghahremani
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: msharifzadeh@sina.tums.ac.ir.
Mohammad
M
Sharifzadeh
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D002338:Carotenoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D008845:Microinjections; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D009538:Nicotine / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors*
D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D002338:Carotenoids; D009538:Nicotine; C029036:crocin
Alzheimer's disease; Antioxidants; Apoptosis; Autophagy; Crocin; Mitochondrial function; Spatial memory