curcumin and Amnesia

Alzheimer’s disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a−1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inhibition of cholinesterase(s). It has been indicated from the current research work that the synthesized curcumin analogs enhanced memory functions in mice models and could be used as valuable therapeutic molecules against neurodegenerative disorders. To determine their exact mechanism of action, further studies are suggested.

Topics: Acetylcholinesterase; Amnesia; Animals; Cholinergic Agents; Cholinesterase Inhibitors; Cholinesterases; Curcumin; Disease Models, Animal; Maze Learning; Mice; Molecular Docking Simulation; Scopolamine

Cognitive decline in dementia is associated with deficiency of the cholinergic system. In this study, five mono-carbonyl curcumin analogs were synthesized, and on the basis of their promising in vitro anticholinesterase activities, they were further investigated for in vivo neuroprotective and memory enhancing effects in scopolamine-induced amnesia using elevated plus maze (EPM) and novel object recognition (NOR) behavioral mice models. The effects of the synthesized compounds on the cholinergic system involvement in the brain hippocampus and their binding mode in the active site of cholinesterases were also determined. Compound

Topics: Amnesia; Animals; Catalytic Domain; Cholinergic Agents; Cholinesterase Inhibitors; Cholinesterases; Cognitive Dysfunction; Curcumin; Dementia; Hippocampus; Humans; Maze Learning; Memory; Mice; Molecular Docking Simulation; Neuroprotective Agents; Oxidative Stress; Scopolamine

In this study, demethylcurcumin (DC), a minor constituent in curcuminoids, showed better anti-acetylcholinesterase (anti-AChE) activities, anti-amyloid β peptide aggregation, neuroprotective activities in 6-hydroxydopamine-treated SH-SY5Y cell models, and anti-nitric oxide production in lipopolysaccharide-treated RAW 264.7 macrophages than those of curcumin. Based on molecular docking analyses with AChE, the meta-hydroxyl group in DC, nonexistent in curcumin, showed the formation of hydrogen bonds with Ser293 and Tyr341 in the binding sites of AChE. For animal experiments, scopolamine-induced amnesia ICR mice were used to analyze the learning and memory functions of DC in comparison with the positive control donepezil. Mice fed with DC (50 mg kg

Topics: Acetylcholinesterase; Amnesia; Animals; Antioxidants; Brain Chemistry; Cholinesterase Inhibitors; Curcumin; Learning; Mice; Mice, Inbred ICR; Models, Molecular; Molecular Docking Simulation; Molecular Structure; Neuroprotective Agents; RAW 264.7 Cells; Scopolamine

Curcuma longa L. is a well-known medicinal plant that has been used for its anti-cancer, neuroprotective, and hepatoprotective effects. However, the neuroprotective effect of fermented C. longa (FCL) has not been reported. Therefore, in this study, the effectiveness of FCL for the regulation of memory dysfunction was investigated in two brain cell lines (rat glioma C6 and murine microglia BV2) and scopolamine-treated mice.. Pretreatment with FCL effectively prevented the cell death induced by oxidative stress in C6 cells. Moreover, FCL inhibited the production NO and PGE. FCL pretreatment could alleviate scopolamine-induced memory impairment in mice, as well as oxidative stress and inflammation in C6 and BV2 cells, respectively. Thus, FCL might be a useful material for preventing impairment of learning and memory.

Topics: Acetylcholinesterase; Amnesia; Animals; Anti-Inflammatory Agents; Antioxidants; Brain; Brain-Derived Neurotrophic Factor; Cell Line; Curcuma; Curcumin; Cyclic AMP Response Element-Binding Protein; Fermentation; Inflammation; Inflammation Mediators; Lipopolysaccharides; Male; Memory Disorders; Mice, Inbred ICR; Neuroprotective Agents; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Scopolamine

In the one-trial taste-avoidance task in day-old chicks, acetylcholine receptor activation has been shown to be important for memory formation. Injection of scopolamine produces amnesia, which appears to be very similar in type to that of Alzheimer's disease, which is correlated with low levels of acetylcholine in the brain. Traditional pharmacological treatments of Alzheimer's disease, such as cholinesterase inhibitors and glutamate receptor blockers, improve memory and delay the onset of impairments in memory compared with placebo controls. These agents also ameliorate scopolamine-induced amnesia in the day-old chick trained on the one-trial taste-avoidance task. The present experiments examined the ability of two less traditional treatments for Alzheimer's disease, phosphatidylserine and curcumin, to ameliorate scopolamine-induced amnesia in day-old chicks. The results showed that 37.9 mmol/l phosphatidylserine and 2.7 mmol/l curcumin significantly improved retention in chicks administered scopolamine, whereas lower doses were not effective. Scopolamine did not produce state-dependent learning, indicating that this paradigm in day-old chicks might be a useful one to study the effects of possible Alzheimer's treatments. In addition, chicks administered curcumin or phosphatidylserine showed little avoidance of a bead associated with water reward, indicating that these drugs did not produce response inhibition. The current results extend the findings that some nontraditional memory enhancers can ameliorate memory impairment and support the hypothesis that these treatments might be of benefit in the treatment of Alzheimer's disease.

Topics: Alzheimer Disease; Amnesia; Animals; Avoidance Learning; Chickens; Cholinergic Antagonists; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Male; Memory; Phosphatidylserines; Reward; Scopolamine

Curcuminoids (a mixture of curcumin, bisdemethoxycurcumin and demethoxycurcumin) share vital pharmacological properties possessed by turmeric, a well known curry spice, considered useful in Alzheimer's disease (AD). The aim of this study was to evaluate if curcuminoids possess acetylcholinesterase (AChE) inhibitory and memory enhancing activities. The in-vitro and ex-vivo models of AChE inhibitory activity were used along with Morris water maze test to study the effect on memory in rats. Curcuminoids inhibited AChE in the in-vitro assay with IC(50) value of 19.67, bisdemethoxycurcumin 16.84, demethoxycurcumin 33.14 and curcumin 67.69 microM. In the ex-vivo AChE assay, curcuminoids and its individual components except curcumin showed dose-dependent (3-10 mg/kg) inhibition in frontal cortex and hippocampus. When studied for their effect on memory at a fixed dose (10 mg/kg), all compounds showed significant (p<0.001) and comparable effect in scopolamine-induced amnesia. These data indicate that curcuminoids and all individual components except curcumin possess pronounced AChE inhibitory activity. Curcumin was relatively weak in the in-vitro assay and without effect in the ex-vivo AChE model, while equally effective in memory enhancing effect, suggestive of additional mechanism(s) involved. Thus curcuminoids mixture might possess better therapeutic profile than curcumin for its medicinal use in AD.

Topics: Acetylcholinesterase; Alzheimer Disease; Amnesia; Animals; Cholinesterase Inhibitors; Curcuma; Curcumin; Dose-Response Relationship, Drug; Hippocampus; Male; Maze Learning; Memory; Parasympatholytics; Phytotherapy; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Scopolamine