Cognitive Enhancing Effects and Antioxidant Activities of Crude Methanol Extracts of Prunus Africana in Scopolamine-Induced Alzheimer’s Disease Mice
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Date
2023
Authors
Ngai, David Nyaga
Journal Title
Journal ISSN
Volume Title
Publisher
Kenyatta University
Abstract
Alzheimer’s disease (AD) is a type of dementia marked by gradual progressive
neurodegeneration caused by excessive neurofibrillary tangles and amyloid beta (Aβ)
build-up in hippocampus and other parts of the brain. Ultimately, this reduces the
number of neurons, synapses and pyramidal nerve connections resulting in
compromised cognitive functions and memory loss. The immune system clears senile
plaques and neurofibrilary tangles oxidatively and in the process, there is excessive
generation of reactive nitrogen and oxygen species that cause the chronic oxidative
stress observed in AD. Conventionally, cholinergic agonists, particularly inhibitors of
acetylcholinesterase including rivastigmine, donepezil and galantamine are the most
commonly used drugs in AD therapy. Unfortunately, their efficacy is low and they
have short half lives hence higher and more frequent dose requirement which is
limited by their side effects that are sometimes unbearable. Fortunately, there are
phytochemicals with AD ameliorating effects. These include phenolic compounds that
clear aggregated amyloid proteins and have antioxidant and anti-inflammatory
properties, steroidal alkaloids that have anti-cholinesterase activity while ascorbic
acid, terpenoids and rivastigmine are not only free radical scavengers but also
stabilizers of muscarinic receptors. Antioxidant activity is a vital requirement for plant
extracts that are used with great success to manage degenerative diseases like AD
since such diseases are usually accompanied by oxidative stress. In the current study,
in vivo cognitive advancing and antioxidant effects of crude methanol extract of stem
bark and leaf of Prunus africana were investigated in scopolamine-induced AD mice.
Morris water maze and Passive avoidance task were used to measure spatial memory
and cognitive enhancing effects of the two plant extracts, respectively. Scopolamine
butylbromide (5mg/kg bw) was administered intraperitoneally to induce AD during
the study. Donepezil (DNP) was used as the standard drug in the current study
because of its ability to improve and maintain high global cognitive potentials and
high torelability. The drug substance, scopolamine, is the most commonly used
substance in biosreening for AD drugs. It is known to lower transcription of brain
derived neurotrophic factor responsible for memory elasticity and development and
also interferes with functioning of muscarinic receptors. The study revealed
phytocompounds with anticholinesterase activity including chlorogenic acid,
pCoumaric acid, vitexin, isovitexin, sitostenone and campesterol. Phytocompounds
with enzymatic antioxidant activity including ursolic acid, campesterol and
sitostenone were also revealed. The two extracts also proved to be rich in
phytochemicals with antioxidant and anti-inflammatory activities which are important
neuroprotective properties. The two extracts significantly improved cognition and
spatial memory in the two behavioural experiments. This was indicated by significant
increase in escape latencies in passive avoidance task and decrease in escape latencies
in Morris water maze tasks in a dose related pattern. These behavioural results are in
collaboration with the anticholisterase, antioxidant and anti-inflammatory activities of
compounds revealed in the two extracts. Generally, the stem bark extract had
significantly higher efficacy than leaf extract in most of the tests carried out. The
disparity in efficacies of the two extracts can be explained in terms of differences in
diversity and proportions of phytochemicals present. From the current study, it is
concluded that crude methanol extracts of stem bark and leaf of P. africana have
several phytocompounds with cognitive and spatial memory enhancing effects,
anticholinesterase and antioxidant activities in scopolamine induced-Alzheimer’s
disease mice.
Description
A Thesis Submitted in Fulfilment of the Requirements for Award of Degree of Doctor of Philosophy (Medical Biochemistry) In the School of Pure and Applied Sciences of Kenyatta University June 2023
Keywords
Cognitive Enhancing Effects, Antioxidant Activities, Crude Methanol Extracts, Prunus Africana, Scopolamine-Induced, Alzheimer’s Disease Mice