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Oxidative stress-induced damage was shown to be one of the important mechanisms to indicate that aluminum has an association with the etiology of Alzheimer's disease (Kumar et al., 2009). Increased generation of reactive oxygen species (ROS) and lipid peroxidation has been found to be involved in the pathogenesis of many diseases of known and unknown etiology and in the toxic actions of many compounds (Andallu and Varadacharyulu, 2003). Aluminium is a nonredox active metal which is capable of increasing the cellular oxidative milieu by potentiating the pro-oxidant properties of transition metals such as iron and copper (Bjertness et al., 1996). An unusual aspect of the biochemistry of this non-redox active metal is its pro-oxidant activity, which might be explained by the formation of an Al superoxide semi-reduced biological macromolecules, including lipids, proteins, nucleic acids, and carbohydrates. The resulting stress increases neuronal death, which contributes to the neuropathology associated with several diseases (Baydas et al., 2003). Gene expression changes in the forebrain occur during normal and pathological aging. Altered gene expression is thought to contribute to the balance between normal aging and age-related memory disorders, including Alzheimer's dis- ease (AD) (Berchtold et al., 2008). Synap- tic dysfunction in AD is apparent before synapse and neuron loss and caused likely by accumulation of β-amyloid (Aβ) pep- tides (Selkoe, 2002). The cellular mecha- nisms underlying synaptic and memory dysfunction caused by altered activity- dependent gene transcription in AD are radical ion (AlO2) (Exley, 2005). It has largely unknown. Understanding the mobeen shown that chronic aluminium exposure is involved in the impairment of mitochondrial electron transport chain (ETC) and increased production of ROS (Kumar et al., 2008). The formation of excessive ROS and reactive nitrogen species (RNS) can lead to oxidative injury. Reactive oxygen species (ROS) interact with all lecular pathways regulating gene expression profiles in memory disorders may allow the identification of new signaling pathways for drug discovery (Altar et al., 2009). Several PCR techniques are used to determine the changes in the gene expression, in which the most aqurat one is Realtime-PCR (RT-PCR). It is became the most popular method of quantitating steady-state mRNA levels (Bustin, 2000). It is most often used for two reasons: either as a primary investigative tool to determine gene expression or as a secondary tool to validate the results of DNA microarrays. Because of the precision and sensitivity of real-time RT-PCR, even subtle changes in gene expression can be detected. Thus real-time PCR can be used to assess RNA levels with great sensitivity and precision. There are several genes play main role in occurrence the AD diseases. The generation of amyloid β-peptide (Aβ) is widely held to play an early and critical role in the pathogenesis of Alzheimer’s disease (Hardy and Selkoe, 2002). Aβ is generated from the large precursor protein amyloid precursor protein (APP) by the sequential action of two proteases, β and γ-secretase. β-secretase has been identified as β-site APP-cleaving enzyme 1 (BACE1) which, together with its homolog BACE2, forms a novel subfamily of transmembrane aspartic proteases within the pepsin family (Vassar and Citron, 2000). The formation of Alzheimer’s Aβ peptide is initiated when the amyloid precursor protein (APP) is cleaved by the enzyme β-secretase (BACE1); inhibition of this cleavage has been proposed as a means of treating Alzheimer’s disease. Cyclooxygenase (COX-2) is continuously expressed within a distinct population of neurons in the brain (Breder et al., 1995), which is a common attribute in enzymes involved in physiological functions of the central nervous system such as memory, sensory integration, and autonomic regulation (Kaufmann et al., 1997). On the other hand, in various neuropathological conditions accompanied by inflammatory reaction, such as stroke (Tomimoto et al., 2000) and amyotrophic lateral sclerosis (ALS) (Yasojima et al., 2001), COX-2 up-regulation is thought to mediate neuronal damage presumably by producing excessive amounts of harmful prostanoids and free radicals. In AD brains, it has been reported that the expression of COX-2 mRNA and protein was elevated (Yasojima et al., 1999). However, it is not yet completely delineated how and in what type of cells COX-2 is increased in the AD brain. Aluminum-induced depletion of antioxidants such as glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) and catalase (CAT) (Mahieu et al., 2005). Antioxidants thus play key roles in the protection against damage caused by reactive oxygen species (Baynes, 1991). Many plant extracts and plant products have been shown to have significant antioxidant activity (Anjali and Manoj, 1995), which may be an important property of medicinal plants associated with the treatment of several diseases including neurodegenerative diseases. Thus, herbal plants are considered useful means to prevent and/or ameliorate certain disorders, such as Alzheimer's disease. Among these herbal resources, the plant Jasonia montana and Jasonia candicans occur in the Mediterranean and surrounding areas (Merxmuller et al., 1977), including the Sinai Peninsula (Tackholm, 1974). The herb has a strong aromatic odor and is used in traditional medicine for diarrhea, stomach ache, and chest diseases (Tackholm, 1969). A literature survey indicated that some mono- and ses- quiterpenes (Ahmed and Jakupovic, 1990; Ahmed, 1991), flavonoids (Ahmed et al., 1989) and essential oils (Hammerschmidt et al., 1993) have been reported from the plant. Rivastigmine is a carbamate derivative pseudo-irreversible cholinesterase inhibitor which can both inhibit acetylcho-linesterase (AChE) and butyrylcholi-nesterase (BuChE1). This drug is licensed for use in the UK for the symptomatic treatment of mild-to-moderately severe AD due to its inhibitory action on AchE activity (Foye et al., 1995). Rivastigmine has been reported to protect mice against cognitive impairment caused by oxygen deficit, improve learning in rats, and antagonize scopolamine induced impairment of cognitive function in rats (Desai and Grossberg, 2001; Howes et al., 2003). It has been demonstrated that Rivastigmine supplementation increased the concentration of acetylcholine and inhibited acetylcholine esterase activity (Liang and Tang, 2004). The present study was designed to investigate the potential role of J. montanta and J. candicans total extracts against AlCl3-induced oxidative stress and gene expression alteration of AD-related enzymes characterizing Alzheimer's disease in male rats. |
