Investigations of the potential effects repeated doses of a hydroethanolic extract of crinum macowanii on memory learning and neuromotor behaviour in two different mouse models of alzheimer's disease.

Abstract

Alzheimer’s disease, the most common form of dementia, is a significant cause of morbidity worldwide. There is no cure for Alzheimer’s disease and current management is only symptomatic. According to Alzheimer’s Disease International, 68% of all people living with dementia will be from lower middle income countries by the year 2050. Galantamine, an alkaloid obtained from Galanthus caucasicus (Amarylildaceae)is an approved treatment of Alzheimer’s disease. Crinum macowanii is a bulbous, alkaloid rich plant which belongs to the same family. Galantamine, Donepezil, Rivastigmine, Tacrine and Memantine are all FDA approved drugs for the management of Alzheimer’s disease, two of which are of herbal origin. Hence, it becomes imperative to research more effective and efficient natural medical treatment options for AD. The primary aim of this study was to investigate if a hydroethanolic extract of Crinum macowanii had any effect on learning and memory behaviour using the Morris Water Maze and the Novel Object Recognition task. Methodology: Two groups of BALB/c mice were used to assess the memory enhancing effects of Crinum macowanii using two different animal models. Namely, the aluminum chloride and scopolamine mouse model. Induction of amnesia was carried out using oral administration of scopolamine in the scopolamine model and oral administration of aluminium chloride in the aluminium chloride mouse model. Crinum macowanii(10, 20, 40 mg/kg) was tested against scopolamine and aluminum chloride induced cognitive decline. The Morris Water Maze and Novel Object Recognition tests were the behavioural models used to assess learning and memory behaviour. Escape latencies and time spent in the target quadrant were measured for the Morris Water Maze while the discrimination index was calculated for the Novel Objection Recognition test.Neuromotor function was assessed using the rotarod test. Biochemical tests to assess the acetylcholinesterase enzyme, antioxidant assays and basic phytochemical analysis were also performed. One-way analysis of variance followed by Tukey’s post hoc test were performed and P<0.05 was considered significant. Results: In the Morris Water Maze test, the Crinum macowanii40 mg/kg group was observed to have a significantly smaller escape latency than the aluminum(26.77s vs 56.43s)and scopolamine(24.1s vs 58.4s)treated groups(P<0.0001). Crinum macowanii40 mg/kg treated mice were also observed to be comparable to the donepezil 3 mg/kg group. During the short-term memory task of the Novel Object Recognition test, it was observed that Crinum macowanii40 mg/kg(59.86%)treated mice had a significantly higher discrimination index than aluminum chloride(49.11%)treated mice (P<0.0316). The same was not observed during the long-term memory phase as no significant difference was seen in the discrimination index between Crinum macowanii and aluminum chloride treated mice(P=0.0621). Against scopolamine induced cognitive decline, the Crinum macowanii group at high doses (40 mg/kg) demonstrated a significantly higher discrimination index than the scopolamine treated mice. Results for the antioxidant assay suggest that the extract of Crinum macowanii possesses antioxidant activity. Results of the rotarod test depict that the extract of the Crinum macowanii40 mg/kg group spent significantly more time on the rotating rod than the scopolamine treated group. Conclusion: The findings of this study suggest that the hydroethanolic extract obtained from the bulbs of Crinum macowanii at a dose of 40 mg/kg improved learning and memory behaviour in the aluminum and scopolamine mouse model. Hence, Crinum macowanii may be useful in the treatment of Alzheimer’s disease and related dementia. However, further studies are recommended which should study the effect of individually isolated alkaloids from Crinum macowanii against cognitive decline.