Nootropic and Neuroprotective Effects of Dichrocephala integrifolia on Scopolamine Mouse Model of Alzheimer’s Disease

Abstract

Alzheimer’s disease the most common form of dementia in the elderly is a neurodegenerative disease that affects 44 millions of people worldwide. The first treatments against Alzheimer’s disease are acetylcholinesterase inhibitors; however, these medications are associated with many side effects. Dichrocephala integrifolia is a traditional herb widely used by indigenous population of Cameroon to treat and prevent Alzheimer’s disease and for memory improvement. In this study, we evaluated the effect of the decoction prepared from leaves of D. integrifolia, on scopolamine-induced memory impairment in mice. Seven groups of six animals were used. The first two groups received distilled water for the distilled water and scopolamine groups. The four test groups received one of the four doses of the decoction of the plant (35, 87.5, 175 or 350 mg/kg p.o.) and the positive control group received tacrine (10 mg/kg), a cholinesterase inhibitor used in the treatment of Alzheimer’s disease, during 10 consecutive days. Scopolamine (1 mg/kg), a cholinergic receptor blocker, administered 30 min after treatments, was used to induce memory impairment to all groups except the distilled water group on day 10 of drug treatment. The behavioral paradigms used to evaluate the effects of the treatment were the elevated plus maze for learning and memory, Y maze for spatial short-term memory, the novel object recognition for recognition memory and Morris water maze for the evaluation of spatial long-term memory. After behavioral tests, animals were sacrificed and brains of a subset were used for the assessment of some biomarkers of oxidative stress (malondialdehyde and reduced glutathione levels) and for the evaluation of the acetylcholinesterase activity. From the remaining subset brains, histopathological analysis was performed. The results of this study showed that, D. integrifolia at the doses of 87.5 and 350 mg/kg significantly (p < 0.01) improved spatial short-term and long-term memory, by increasing the percentage of spontaneous alternation in the Y maze and reducing the escape latency in the Morris water maze. Furthermore, the results of histopathological evaluation showed that D. integrifolia attenuated the neuronal death in the hippocampus induced by scopolamine. The main finding of this work is that D. integrifolia improves learning capacities and counteracts the memory impairment induced by scopolamine. Thus, D. integrifolia can be a promising plant resource for the management of Alzheimer’s disease and memory loss.

Effect of Ganoderma lucidum on memory and learning in mice

“…The acetylcholinesterase determination has supported the results of elevated plus maze and Morris water maze test activity of mice in which the statistical reduction in the AChE activity caused the increment in the acetylcholine level in the brain of the mouse which resulted in increased function of memory. Therefore, the current study suggests that the ethanol extract of Ganoderma lucidum has dose dependent potential on cholinergic neuronal system and this resulted in elevating the brain acetylcholine level which resulted in improvement of memory function [30,32]. ; The values are mean ± SEM (One-way ANOVA followed by Tukey's Post hoc test).…”

“…ap < 0.05, bp < 0.01, cp < 0.001 when compared with scopolamine alone treated group. *p < 0.05, **p < 0.01, ***p < 0.0001 when compared with DW treated (control) group DW, distilled water; GLE 150, Ganoderma lucidum extract (150 mg/kg); GLE 300, Ganoderma lucidum extract 300/kg; Scop, Scopolamine; Physo, Physostigmine Ganoderma lucidum improved the learning task and retained the information [10,21,30].…”

“…Scopolamine is an alkaloidal drug which is extracted out from Datura stramonium. Scopolamine has tendency to impair memory in humans and animals, that is why it is used to cause long term or short-term memory impairment in rodents [30].…”

“…Drugs which have potential of increasing the cholinergic neuronal activity, are effective against memory impairment. Physostigmine is one of the drugs which increases cholinergic neuronal activity in brain and can combat the memory impairment [30].…”

The use of nootropics in Alzheimer’s disease: is there light at the end of the tunnel?

“…To gain more insight into the pharmacodynamics of nootropics, recent studies on cell lines as well as review papers were also considered. Dichrocephala integrifolia improved cognitive deficits and attenuated neuronal death on scopolamine-induced mouse model of AD 43 , while Pharmaceutical substance (PhS) based on amide form Human leukemia differential factor -6 (AF HLDF-6) restores cognitive dysfunction in C57B1/6 transgenic mouse model of AD 44 . Further, fisetin reverses synaptic dysfunction, prevented neuroinflammation, and improves memory in C57BL/6N transgenic mouse model of cognitive dysfunction 45 , and Cerebrolysin showed its neuroprotective potential by protecting grafted Neural stem cells (NSCs) in an APP Transgenic mice model of AD, hence it could be a potential adjuvant therapy for AD when combined with grafting 46 .…”