lignans and Amnesia

Recently, our research team reported the anti-amnesic potential of desalted-hydroethanolic extracts of Salicornia europaea L. (SE-EE). In this study, we performed bioactivity-guided isolation and identification of Acanthoside B (Aca.B), from SE-EE, as the potential bioactive candidate and examined anti-amnesic activity with its potential mechanism of action using an in vivo model. S7-L3-3 purified from SE-EE showed enhanced in vitro acetylcholinesterase (AChE) inhibitory activity. The isolated S7-L3-3 was identified and characterized as Aca.B using varied spectral analyses, i.e., Nuclear magnetic resonance (NMR), Ultraviolet-visible (UV-Vis), and Electrospray ionization-mass spectrometry (ESI-MS). In the in vitro studies, Aca.B exhibited negligible toxicity and showed a dose-dependent nitric oxide inhibitory potential in Lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. In the in vivo studies, the oral administration of Aca.B to mice showed enhanced bioavailability and dose-dependent repression of the behavioral/cognitive impairment by regulating the cholinergic function, restoring the antioxidant status, attenuating the inflammatory cytokines/mediators and actively enriching neurotropic proteins in the hippocampal regions of the scopolamine-administered mice.

Topics: Amnesia; Animals; Brain-Derived Neurotrophic Factor; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Furans; Glucosides; Inflammation; Lignans; Membrane Glycoproteins; Mice; Oxidation-Reduction; Protein-Tyrosine Kinases; Receptors, Cholinergic; Scopolamine

Acetylcholinesterase (AChE) inhibitors represent a major class of drugs which provide symptomatic relief and improvement in cognitive function in Alzheimer's disease (AD). In this study, cubebin, a dibenzylbutyrolactone lignan, was isolated from Piper cubeba and investigated for its AChE inhibitory activity in an attempt to explore its potential for memory-enhancing activities in mice.. Molecular docking of cubebin was carried out followed by in vitro AChE activity. Mice were treated with cubebin (25 & 50 mg/kg; i.p.), for three days and memory impairment was induced by scopolamine (3 mg/kg; i.p.). Memory function was evaluated by Morris water maze (MWM) test. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain.. Molecular docking study revealed that cubebin was well bound within the binding site of the AChE enzyme showing interactions such as π-π stacking and hydrogen bonding with residues present therein. Cubebin inhibited AChE enzyme in an in vitro assay with IC50value of 992 μM. Scopolamine administration caused a significant impairment of learning and memory in mice, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and oxidative stress in mice brain. Pre-treatment of cubebin (25 and 50 mg/kg; i.p.) significantly prevented scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and oxidative stress level.. Cubebin showed promising protective activity in scopolamine-induced spatial memory impairment in mice. This could be attributed to its brain AChE inhibition and antioxidant activity.

Topics: Acetylcholinesterase; Amnesia; Animals; Brain; Cholinesterase Inhibitors; Furans; Humans; Lignans; Maze Learning; Mice; Molecular Docking Simulation; Neuroprotective Agents; Oxidative Stress; Scopolamine

Gomisin A is a component of the fruits of Schizandra chinesis which are widely used as a tonic in traditional Chinese medicine. In the present study, we assessed the effect of gomisin A on the learning and memory impairments induced by scopolamine. The cognition-enhancing effect of gomisin A was investigated using a passive avoidance test, the Y-maze test, and the Morris water maze test in mice. Drug-induced amnesia was induced by treating animals with scopolamine (1 mg/kg, i.p.). Gomisin A (5 mg/kg, p.o.) administration significantly reversed scopolamine-induced cognitive impairments in mice by the passive avoidance test and the Y-maze test (P<0.05), and also improved escape latency in the Morris water maze test at 5 mg/kg (P<0.05). Moreover, in an in vitro study, gomisin A was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC50 value; 15.5 microM). These results suggest that gomisin A may be a useful cognitive impairment treatment, and its beneficial effects are mediated, in part, via enhancing the cholinergic nervous system.

Topics: Acetylcholinesterase; Amnesia; Animals; Avoidance Learning; Cholinesterase Inhibitors; Cognition; Cyclooctanes; Dioxoles; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Lignans; Male; Maze Learning; Memory; Mice; Mice, Inbred ICR; Scopolamine

Our previous study indicated that the water layer present in Fructus Schisandra(FS(w)) at 10 and 25 mg kg(-1)significantly counteracted cycloheximide (CXM)-induced amnesia. Therefore, the mechanism of action of the ameliorating effect of FS(w)on CXM-induced amnesia in the passive avoidance task was investigated in rats. The ameliorating effect of FS(w)on CXM-induced amnesia was depressed by scopolamine. The serotonin releaser, p -chloroamphetamine significantly antagonized the ameliorating effect of FS(w)on CXM-induced amnesia. Furthermore, the ameliorating effect was also inhibited by the 5-HT(1A)receptor agonist 8-OH-DPAT, but potentiated by the 5-HT(2)receptor antagonist ritanserin. Finally, the GABA(A)receptor antagonist bicuculline blocked the ameliorating effect of FS(w). These results suggest that the beneficial effect of FS(w)on CXM-induced amnesia is amplified by treatment with serotonergic 5-HT(2)receptor antagonists, but reduced by serotonergic 5-HT(1A)receptor agonists as well as GABA(A)and cholinergic receptor antagonists.

Topics: Administration, Oral; Amnesia; Animals; Bicuculline; Cycloheximide; Cyclooctanes; Drugs, Chinese Herbal; Lignans; Male; p-Chloroamphetamine; Phytotherapy; Plants, Medicinal; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Reaction Time; Receptors, Neurotransmitter; Ritanserin; Scopolamine; Water

To study the action mechanism of a new cognition enhancer clausenamide and the effect of clausenamide on regional acetylcholine (ACh) levels, and to examine anisodine-induced ACh decrease in mice of memory deficits, and to compare the effect of (-)clausenamide on ACh with that of (+)clausenamide.. Animal amnesia model was induced by i.p. anisodine and brain ACh content was measured by high performance liquid chromatography with electrochemical detection.. Single administration of (-)clausenamide or (+)clausenamide (10, 20, 50 mg/kg, i.g.) had no effect on the ACh level in the frontal cortex, hippocampus and striatum. However, pretreatment with (-)clausenamide (10, 20, 50 mg/kg, i.g.) significantly ameliorated the reduction of ACh induced by anisodine (10 mg/kg, i.p.) in a dose-dependent manner. Physostigmine (0.2 mg/kg, s.c.), as a cholinesterase inhibitor significantly increased the ACh levels and reversed the anisodine-induced ACh decrease. In contrast, (+)clausenamide had no effect on ACh decrease in all examined brain regions. (-)Clausenamide ameliorated anisodine-induced memory deficits in step-through test in mice.. There is significant difference in the action of (-)clausenamide and (+)clausenamide. The protective action of (-)clausenamide against anisodine-induced amnesia is due to its ability to reverse the ACh reduction.

Topics: Acetylcholine; Amnesia; Animals; Brain; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Lactams; Lignans; Mice; Random Allocation; Scopolamine Derivatives; Stereoisomerism

The effect of a new cognition enhancer clausenamide on regional acetylcholine (ACh) levels and anisodine-induced ACh decrease were examined in mice of memory deficits. In the mean time, the effect of (-)clausenamide on ACh was compared with that of (+)clausenamide. Animal amnesia model was induced by i.p. anisodine, brain acetylcholine content was measured by high performance liquid chromatography with electrochemical detection. It was found that single administration of (-)clausenamide or (+)clausenamide(10, 20, 50 mg.kg-1, ig) showed no effect on the ACh level in the frontal cortex, hippocampus and striatum in normal condition. However, pretreatment with (-)clausenamide (10, 20, 50 mg.kg-1, ig) significantly ameliorated the reduction of ACh in these regions induced by anisodine (10 mg.kg-1, i.p.) in a dose-dependent manner. In the meantime, (-) clausenamide ameliorate anisodine-induced memory deficits in step-through test in mice. In contrast, (+)clausenamide showed no effect on these sides. The results indicate that there is significant difference between the actions of (-)clausenamide and (+)clausenamide; The protective action of (-)clausenamide against anisodine-induced amnesia is due to its ability to reverse ACh reduction.

Topics: Acetylcholine; Amnesia; Animals; Brain; Drugs, Chinese Herbal; Lactams; Lignans; Male; Mice; Rutaceae; Scopolamine Derivatives; Stereoisomerism