الفهرس 
REVIEW OF THE LITERATUREOnly 14 pages are availabe for public view
 |  | from | 371 |  |  |
| | | from | 371 | | |
Abstract
7. SUMMARY AND CONCLUSION
A) SUMMARY:
• The current study was aimed to evaluate the efficiency of Salvia triloba, Piper nigrum, Ruta graveolens and Pegenum harmala extracts in the management of neuroinflammatory insults and neuronal apoptosis characterising AD in experimentally-induced animal model.
• The current study was designed to study acute and chronic toxicities of the selected medicinal plants total extract on male and female rats.
The preclinical toxicological study for the selected medicinal plant extracts (Part I) was conducted from one hundred and sixty eight adult Sprague Dawley rats (eighty four male and eighty four female). On the other hand, the pharmacological study (Part II) was conducted from one hundred and ten adult male Sprague Dawley rats. The rats were weighing from 150 to 200 g, 4 months old obtained from the Animal House Colony of the National Research Centre (NRC), Cairo, Egypt. The animals were maintained on standard laboratory diet and water ad libitum, housed in stainless steel cages in a temperature controlled (23 ± 1ºC) and artificially illuminated (12 h dark/light cycle) room free from any source of chemical contamination. All animals received human care and use according to the guidelines for Animal Experiments which were approved by the Ethical Committee of Medical Research, National Research Centre, Egypt. Alzheimer’s disease was induced in the experimental animals by using AlCl3 orally in a dose of 17 mg/kg b. wt daily for one month (Krasovskii et al., 1979). After an acclimization period of one week, the animals were classified into seven main groups:
group (1): Normal healthy animals served as negative control group.
group (2): AD-induced group.
group (3): AD-induced group treated orally with the conventional therapy for AD (Rivastigmine) in a dose of 0.3 mg/kg b.wt (Carageorgious et al., 2008) daily for three months (after stopping AlCl3 administration (1 month, induction of AD))
group (4): AD-induced group divided into two subgroups, the first subgroup was treated orally with S. triloba extract in a dose of 750 mg/kg b. wt. and the second subgroup was treated orally with S. triloba extract in a dose of 375 mg/kg b. wt. (the most save dose and the half of the most of save dose respectively, which was obtained in the chronic study) daily for three months (after stopping AlCl3 administration (1 month, induction of AD))
group (5): AD-induced group divided into two subgroups, the first subgroup was treated orally with P. nigrum extract in a dose of 187.5 mg/kg b. wt. and the second subgroup was treated orally with P. nigrum extract in a dose of 93.75 mg/kg b. wt. (the most save dose and the half of the most of save dose respectively, which was obtained in the chronic study) daily for three months (after stopping AlCl3 administration (1 month, induction of AD))
group (6): AD-induced group divided into two subgroups the first subgroup was treated orally with R. graveolens extract in a dose of 750 mg/kg b. wt. and the second subgroup was treated orally with R. graveolens extract in a dose of 375 mg/kg b. wt. (the most save dose and the half of the most of save dose respectively, which was obtained in the chronic study) daily for three months (after stopping AlCl3 administration (1 month, induction of AD))
group (7): AD-induced group divided into two subgroups the first subgroup was treated orally with P. harmala extract in a dose of 375 mg/kg b. wt. and the second subgroup was treated orally with P. harmala extract in a dose of 187.5 mg/kg b. wt. (the most save dose and the half of the most of save dose respectively, which was obtained in the chronic study) daily for three months (after stopping AlCl3 administration (1 month, induction of AD))
At the end of the experimental period, rats were scarified after 3 months, at the end of the experiment, the animals were kept fasting for 12 hours and the rats were killed by decapitation, blood specimens were collected after 18 hours fasting using the orbital sinus technique, under light anesthesia by diethyl ether, according to the method. Each blood specimen was left to clot in clean dry test tubes, and then centrifuged at 3000 rpm for ten minutes to obtain serum. The clear serum was then frozen at -20 ºC for the biochemical analyses.
The whole brain of each animal was rapidly dissected, thoroughly washed with isotonic saline, dried and then weighed. One half of each brain was homogenized immediately to give 10% (w/v) homogenate in ice-cold medium containg 50 mM Tris-HCl (pH 7.4) and 300 mM sucrose. The homogenate was centrifuged at 3000 rpm for 10 min at 4 ºC. The supernatant (10%) was separated for biochemical analyses (Brain Ach level as well as Brain and serum AChE activities, CRP, NF-kappa B65, MCP-1, COX-2, LTB4 and Bcl-2 levels). Also, brain total proteins concentration was measured to express the concentration of different brain parameters per mg protein. The second portion of each brain was fixed in formalin buffer (10%) for histological investigation of all studied groups.
The results of the present study were as follows:
1. In comparison with negative control group, Alcl3 administration induced significant elevation in brain and serum AChE, CRP, total NF Kappa B65, MCP-1, COX-2 and LTB4 activities and significant reduction in brain Ach as well as brain and serum Bcl-2 levels. Also. Micrographs of brain section of AD group showing sever congestion in the blood vessels with oedema in the memninges. The cerebrum showed neuronal degeneration with oedema and gliosis in between, associated with focal gliosis in the cerebrum. The hippocampus showed encephalomalacia and plagues formation.
2. Treatment of AD-induced rats with Rivastigmine and/or the selected medicinal plants total methanolic extract produced significant decrease in brain and serum AChE, CRP, total NF Kappa B65, MCP-1, COX-2 and LTB4 activity with concomitant significant elevation brain Ach as well as brain and serum Bcl-2 levels in comparison with Al-intoxicated positive control group. Also, treatment with these extracts caused improvement in measured histological feature.
B) CONCLUSION:
• The current study revealed that treatment of AD-induced rats with S. triloba, P. nigrum, R. graveolens or P. harmala methanolic extracts, significantly ameliorates the cholinergic dysfunction, inflammation and apoptosis induced neurodegeneration characteristic of AD. These effects could be attributed to powerful antiinflammatory activity, the anticholinesterase effects, antioxidant capacity as well as anti-apoptotic effects. Noteworthy, R. graveolens extracts revealed more pronounced modulatory effect on most of the measured biochemical parameters as well as histopathological feature of the brain.
• These results represented good therapeutic approaches for intervension against progressive neurological damage associated with AD with special reference to the inflammatory insults.