INFLUENCE OF CURCUMIN ON CYTOKINES CONTENT AND ANGIOTENSIN-CONVERTING ACTIVITY UNDER INTRAHIPPOCAMPUS ADMINISTRATION OF β-AMYLOID PEPTIDE IN RATS

Abstract

Curcumin (diferuloylmethane) is a natural polyphenol which manifests compound effect on the body homeostasis; it negatively influences the NF-kB and АР-1 transcription factors, suppresses expression of cyclooxygenase-2, lipoxygenase, NO-synthase, matrix metalloproteinase-9, urokinase of plasminogen type activator, tumor necrosis factor (TNF), chemokines, molecules of cell adhesion and cycline D1; it inhibits expression of growth factor receptors and activity of stress-associated proteinkinase (JNK), protein tyrosine kinases, as well as other protein serine/threonine kinases [1–3]. Curcumin also acts as inhibitor of DNA-methyltransferase, therefore it is regarded as DNA hypomethylating agent. It establishes balance between activity of histone acetyltransferase and histone deacetyltransferase thus influencing the expression of certain genes. At last, curcumin modulates activity of micro-RNAs and their numerous target genes [4–5]. The above-mentioned effects of curcumin are accumulated in its anti-oxidation, anti-inflammation, anti-tumor and anti-amyloidogenic properties [6–11]. Considered recently as one of probable Alzheimer’s disease (AD) factors is aggregation of -amyloid peptide (А) to fibrils or deposits as the main pathogenetic event [12–15]. In particular, several studies showed that А is essentially accumulated in the brain areas (hippocampus and cortex), which conduce to obtaining and processing of information, and memory [16–18]. This peptide is formed during amyloidogenic processing of amyloid protein precursor (АРР) [19–21]. In a non-amyloidogenic way the full-size APP is decomposed by - and -secretases within Golgi apparatus and plasmatic membrane without forming the -amyloid peptide. Back internalization of a certain part of APP from the plasmatic membrane ant its transport towards the late endosomes results in - and -secretase-associated separation of А isoforms, 38 to 43 amino acid residues long [22]. The role of switch between non-amylodogenic and amyloidogenic ways of APP processing is