Thesis (M.Sc.)-Cairo University, 2022.

Bibliography: pages 129-172.

Dementia is a broad range of neurodegenerative diseases characterised by a significant deterioration in cognitive capacity that interferes with daily activities. Alzheimer's disease (AD) is the most common type of dementia, accounting for 60% and up to 80 % of all dementia cases.According to the Global Burden of Disease Study, Alzheimer's disease is one of the top causes of death that is rapidly increasing.About 10% of people of age 65 and older suffer from AD .In the recent decade, epidemiologic data has revealed a significant increase in the incidence of Alzheimer's disease: According to estimates, the number of people living with Alzheimer's disease would rise from 26.6 million in 2006 to 107 million by 2050, with 16.5 million in Europe. To note, 68% of the increase would be localized in the low- and middle-income countries.
The primary histopathologic lesions of AD are the extracellular amyloid plaques and the intracellular Tau neurofibrillary tangles (NFTs).Progressive neuronal death results in a deficiency and imbalance of numerous neurotransmitters (e.g., acetylcholine, dopamine, and serotonin), as well as the cognitive deficits found in Alzheimer's disease.
All of the currently available treatments aim to correct the disease's neurotransmitter imbalance. Donepezil, galantamine, and rivastigmine are three acetylocholinesterase inhibitors (AChEIs) that have been licenced and N-methyl D-aspartate-receptor antagonists for the treatment of Alzheimer's disease. The main side effects of these drugs include diarrhea, nausea, loss of appetite and sleep disturbances. In people with certain heart disorders, serious side effects may include cardiac arrhythmia.
Memantine is a term that refers to a (Namenda). This medicine reduces the progression of symptoms in those with moderate to severe Alzheimer's disease by acting on a different brain cell communication network. It's sometimes combined with a cholinesterase inhibitor to get the best results. Dizziness and disorientation are two rather uncommon side effects.
Functional foods are a promising topic of study that is currently garnering attention for their potential to prevent and/or treat a variety of disorders, including neurodegenerative diseases. As a result, the current study's aim was to investigate whether traditional herbs like Punica granatum and Persea americana extracts can reduce the progression of Alzheimer's disease in experimental animals caused by AlCl3.
Punica granatum has anti-oxidant, anti-viral and anti-tumor properties and is said to be a good source of vitamins, especially vitamin A, vitamin C, and vitamin E, as well as folic acid. Punica granatum is rich in anti-oxidants and thus protects our body from free radicals. Punica granatum improves memory. Certain compounds in Punica granatum exhibit strong antiplaque effects.
Persea americana are high in vitamins, minerals, and healthy fats, which assist to prevent disease and maintain your body in good operating order. Persea americana may help ward off: cancer, Arthritis and osteoporosis: The vitamin K in Persea americana boosts your bone health by slowing down bone loss and warding off osteoporosis,depression: Depression and low folate levels have been linked in studies. Folate prevents the buildup of a chemical in your blood called homocysteine. Homocysteine causes depression by slowing the supply of nutrients to the brain. Persea americana ' high folate content may aid in the prevention of depression symptoms and inflammation: Chronic inflammation can kick off many diseases, including diabetes, Alzheimer’s disease, and arthritis. The vitamin E in Persea americana lowers inflammation in your body.
To evaluate the effect of Punica granatum and Persea americana extracts on Alzheimerʾs disease ,an experimental study done on 42 white A mature male Wister albino rats Rattus norveegicus were used. Their weights ranged between 170-180 gm, at the beginning of the experiment. For one week, they were confined in adequate cages to allow them to adjust to laboratory conditions. Rodent pellets and fresh tap water were always available. The animals were received AlCl3 (17mg/kg body weigh) orally daily for one month. Diseased animals received Punica granatum extract (40 mg/kg b. w.), Persea americana extracts (33.3 mg / kg b. w. ) orally on daily for 3 months and reference drug Aricept (0.4 mg/kg b.w.) 2 weeks orally and their effects were determined after the administration of the last dose.

Study design:
Animals were divided into seven groups (n = 6) and treated orally as follows:
- Group 1 Negative control (G1) animals were orally received distilled water.
- Group 2 Positive control (G2) animals were orally received AlCl3 daily for one month.
- Group 3 Treated group animals were orally received Punica granatum extract.
- Group 4 Treated group animals were orally received Persea americana extract.
- Group 5 Reference group (G5) animals were orally received Aricept for two weeks.
To study any effect of different extracts (if present) on the experimental animals two groups where studied (G6 and G7) without any exposure to AlCl3.
- Group 6 Animals were orally received P.granatum extract.
- Group 7 Animals were orally received P.americana extract.
- After one month of experiment, the blood samples and brain tissues from positive control (G2) animals were collected. After two weeks of treatment by Aricept blood samples and brain tissues were collected from treated group (G5) . After three months of treatment rats were scarified ,blood samples and brain tissues of treated groups (G3 and G4),negative control (G1) and protected groups (G6 and G7 ) were collected in clean eppendorff tubes containing disodium EDTA as anticoagulant for comet assay. In addition, other blood samples were collected into plain tubes for obtaining the serum by using the cooling centrifuge . Finally the serum was stored at -20 °C for laboratory assessment of liver function tes (AST,ALT),kidney function test (urea,creatinin) and lipid (cholesterol, triglycerides). Portion of the brain tissues were removed and were frozen for determination of dopamine , caspase 3 and the remaining brains were fixed in 10% buffered-saline formalin for histopathologic evaluation.
Result obtained from this study demonstrated that:
- There was significant decreased mean level of dopamine in brain tissue in positive control compared to negative control and significant increased mean level of dopamine in brain tissue in treated groups compared to positive group.
- There was Significant increased mean level of caspase 3 in brain tissue in positive control compared to negative control and significant decreased mean level of caspase 3 in brain tissue in treated groups compared to positive group.
- There was Significant increased mean level of comet in whole blood in positive control compared to negative control and significant decreased mean level of comet in treated groups compared to positive group.
- Histological investigation results showed in negative control normal neurons, positive control showing focal gliosis and congested blood vessel, Punica granatum extract treated group showing increase number of mature cells and few glial cells , Persea americana extract treated group showing scattered glial cells, few numbers of mature neuronal cells and reference drug (Aricept) group showing dilated congested vascular area surrounded by glial and neuronal cells in neurofibrillary background.
- There were significant increased mean level of liver function in blood in positive control compared to negative control and significant decreased mean level of liver function in blood in treated groups compared to positive control.
- There was significant increased mean level of urea in blood in positive control compared to negative control and significant decreased mean level of urea in blood in treated groups compared to positive control.
- There was significant increased mean level of cholesterol in blood in positive control compared to negative control and significant decreased mean level of cholesterol level in treated groups compared to positive control.
- There was significant increased mean level of TG in blood in positive control compared to negative control and significant decreased mean level of TG in blood in treated groups compared to positive control.

خلفية:مرض الزهايمر هو مرض تنكسي عصبي تقدمي.يتم تعريفه من خلال التواجد المشترك لصفائح أميلويد بيتا خارج الخلية (Aβ) المكونة أساسًا من التشابك الليفي العصبي AB المترسب وداخل الخلايا المكونة من بروتين تاو مفرط الفسفرة وغير طبيعي. هدف:هدفت هذه الرسالة الى معرفة دور مستخلصات الرمان والافوكادو كعامل فى تقليل التاثيرات التنكسية العصبية لسمية كلوريد الالمونيوم فى ذكور الجرذان. طُرق:تم تقسيم 42 من ذكور الجرذان إلى سبع مجموعات تجريبية.مجموعة المراقبة السلبية (1) مجموعة التحكم الإيجابية(2),(3),(4),(5) تلقت كلوريد الالمونيوم(17 مجم/كجم من وزن الجسم) يوميا لمدة شهرو عولجت بمستخلصات الرمان(40مجم/كجم من وزن الجسم) والافوكادو(33.3مجم/كجم من وزن الجسم)لمدة ثلاثة شهوروالعلاج المرجعى(0.4مجم/كجم من وزن الجسم)لمدة اسبوعين على التوالى. النتائج: انخفض متوسط مستوى الدوبامين في أنسجة المخ في مجموعة التحكم الإيجابية بشكل ملحوظ مقارنة بالتحكم السلبي ،بينما تمت زيادة كاسباس 3 وتفتيت الحمض النووي بشكل ملحوظ. خففت معالجة مستخلصات الرمان والافوكادومن التأثيرالضار لـكلوريد الالمونيوم فى المجموعات المعالجةوعززت مستوى الدوبامين وقللت من علامات موت الخلايا المبرمج. استنتاج:الرمان والافوكادو لهما تاثيرلتقليل التاثير التنكسى العصبى لمرض الزهايمر.

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