PHD-Department of Biochemistry and Biotechnology

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Browsing PHD-Department of Biochemistry and Biotechnology by Subject "Antioxidant Activities"

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    Cognitive Enhancing Effects and Antioxidant Activities of Crude Methanol Extracts of Prunus Africana in Scopolamine-Induced Alzheimer’s Disease Mice
    (Kenyatta University, 2023) Ngai, David Nyaga; Mathew Piero Ngugi; Cromwell Mwiti Kibiti
    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.
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    Phytochemical Profiles, Antiproliferative and Antioxidant Activities of Carissa Edulis (Forssk.) Vahl) and Pappea Capensis (L.) Extracts
    (2022) Muruthi, W. Carolyn; Mathew Piero Ngugi; Steven Maina Runo
    Cancer mortality is a global concern. In Kenya, cancer is ranked third cause of death. Incidence rates for breast and prostate cancers exceed those of other forms of cancer. Reactive species are implicated in all aspect of cancer, that is, initiation, promotion progreesion. With the increased changes in lifestyle and environmental pollutants; the burden caused by cancer will continue to have an upward trajectory. The current therapeutic approaches despite showing efficacy are characterized by several limitations such as adverse effects, prohibitive costs and sturdy resistance. This drives the need to explore alternative anticancer drugs. Several studies have evaluated anticancer and antioxidant effects of diverse plant extracts. In addition, toxicity effect of herbal plants has been evaluated using various assays including brine shrimp (Artemia salina) lethality assay. C. edulis and P. capensis are used as traditional therapy among the African communities to manage cancer and oxidative stress-related ailments. However, there is limited research on the antiproliferative and antioxidant effects of these medicinal plants. The current study, therefore, sought to evaluate the phytochemical profile, antiproliferative, antioxidant and in vivo cytotoxicity activities of C. edulis and P. capensis extracts. Samples were collected from Embu County, Kenya. Phytochemical profiles were determined using Liquid Chromatography Mass Spectrophotometer (LCMS) and Gas Chromatography Mass Spectrophotometer (GC-MS) analyses. Antiproliferative activity of the plant extracts against breast cancer (HCC 1395), prostate cancer (DU145) and Vero (normal) cell lines was determined using MTT assay. Effect of the extracts on expression of apoptotic genes (p53, bax and HOXB13) was evaluated using quantitative Real Time Polymerase Chain Reaction (qRTPCR). In vitro antioxidant properties of the extracts were evaluated through ferric reduction, Iron chelating, hydroxyl radical, and I, I-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities. Activities of catalase, superoxide dismutase and glutathione reductases of the extracts were further determined. Toxicity of the extracts against was determined using the brine shrimp lethality test (BSLA). The results indicated that ethyl acetate extracts of C. edulis and P. capensis had the highest activity against cancer cells with IC50 values of 2.12±0.02, and 6.57±0.03μg/ml on HCC 1395 and 2.92±0.17 and 5.00±0.17μg/ml on DU145, respectively. Moreover, all the extracts exhibited relatively less cytotoxic activities against Vero cell lines (IC50>20μg/ml). The extracts also exhibited selectivity againt the cancer cells (SI>3). Further, mRNA expression of p53 in the treated HCC 1395 was increased by 7 and 3-fold, whereas by 3 and 2-fold in DU145 cells, upon treatment with ethyl acetate extracts of C. edulis and P. capensis, respectively. Similarly, severalfold increases were observed in the number of transcripts of Bax in HCC 1395 and HOXB13 in DU145 cells. The extracts had antioxidant activities whereby IC50 values were less than 50mg/ml, indicating strong scavenging activities. BSLA assay indicated that the extracts were non-toxic (LC50≥1000μg/ml) and had low toxicity (LC50≥500- 1000μg/ml) effects against A. salina. Phytochemical analyses revealed presence of compounds which are associated with antiproliferative and antioxidant activities including flavonoids, phenolics, tocopherols and terpenoids. The findings provide a scientific validation for the folklore use of C. edulis and P. capensis in management of cancer and oxidative stress. Nevertheless, there is a need for further purification and characterization of phytochemicals associated with anticancer and antioxidant activities. In addition, further toxicity assays should be conducted to explore effects of extracts on organs weight, body weight, haematological and biochemical parameters.