Cognitive Enhancing Effects and Antioxidant Activities of Crude Methanol Extracts of Prunus Africana in Scopolamine-Induced Alzheimer’s Disease Mice

dc.contributor.advisorMathew Piero Ngugien_US
dc.contributor.advisorCromwell Mwiti Kibitien_US
dc.contributor.authorNgai, David Nyaga
dc.date.accessioned2023-08-09T08:20:50Z
dc.date.available2023-08-09T08:20:50Z
dc.date.issued2023
dc.descriptionA 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 2023en_US
dc.description.abstractAlzheimer’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.en_US
dc.description.sponsorshipKenyatta Universityen_US
dc.identifier.urihttp://ir-library.ku.ac.ke/handle/123456789/26670
dc.language.isoenen_US
dc.publisherKenyatta Universityen_US
dc.subjectCognitive Enhancing Effectsen_US
dc.subjectAntioxidant Activitiesen_US
dc.subjectCrude Methanol Extractsen_US
dc.subjectPrunus Africanaen_US
dc.subjectScopolamine-Induceden_US
dc.subjectAlzheimer’s Disease Miceen_US
dc.titleCognitive Enhancing Effects and Antioxidant Activities of Crude Methanol Extracts of Prunus Africana in Scopolamine-Induced Alzheimer’s Disease Miceen_US
dc.typeThesisen_US
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