In many chronic neurodegenerative diseases including Alzheimer's disease (AD), chronic activation of microglia can be observed. Microglia, the resident macrophages of the central nervous system, are found in increased numbers surrounding senile amyloid plaques which play a central role in the inflammatory cascade. Macrophages were reported to contribute amyloid angiopathy and massive neuronal tissue destruction is also reported due to high macrophage number. It is also evidenced that COX-2-positive macrophages infiltrate into AD brain damage the blood-brain barrier. In autoimmune animal models, these two related cell types, microglia and macrophages were involved in brain pathology in multiple sclerosis and experimental allergic encephalomyelitis. When activated both secrete a variety of cytokines, including interleukin-1, interleukin-6, and tumor necrosis factor as well as reactive oxygen and nitrogen species (ROS/RNS). Since ROS act as signaling molecules in proinflammatory redox-active signal transduction pathways, it is likely that intracellularly acting plant derived antioxidants, including polyphenols, have been shown to scavenge these "signaling" reactive oxygen species, and thus perform in an anti-inflammatory capacity. Also opportunities exist via diet and lifestyle for contributing to chronic inflammation or alternatively exert anti-inflammatory activity.\ud
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A selection of Chinese medicinal plants and a sample library from the CSIRO including plant and fungal material such as fruit, leaves, stems, roots, tubers, seeds, juice and pulp, as well as food processing co-products or waste material, for example spent grain from brewing, were tested for ability to attenuate NO and TNF-α production, in vitro. The most potent of them was selected by a high through put screening procedure, involving murine microglia and macrophages. Considering the stability of activity during processing stages (patented processing methods of the CSIRO plant and food library), activity on both the cell lines and suppression of both NO and TNF-α without cytotoxicity, C.zeylanicum has been selected as the lead candidate for further chemical analysis. Though a variety of cinnamon species were extensively studied for the anti-oxidant, anti-diabetic, anti-microbial, anticancer and anti-arthritis properties, there was not much evidence in support of anti-inflammatory properties especially relevant to the species C.zeylanicum.\ud
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We have identified the presence of 9 bioactives in dried powder of C.zeylanicum bark, namely β-caryophyllene, p-cymene, cinnamaldehyde, 2-methoxy cinnamaldehyde, α-amyl cinnamaldehyde, citral, benzyl benzoate, furfural, cinnamyl alcohol. β-caryophyllene, p-cymene, cinnamaldehyde and its derivatives 2-methoxy cinnamaldehyde and α-amyl cinnamaldehyde, citral, benzyl benzoate and furfural have shown both NO and TNF-α inhibitory activity while cinnamyl alcohol and eugenol have shown NO inhibitory activity but not TNF-α inhibition. Neither of these constituents showed significant levels of cytotoxicity at doses inhibiting NO (percentage cell viability <80%), but citral, pcymene and α-amyl cinnamaldehyde showed cell death at IC₅₀ doses of TNF-α inhibition.\ud
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In conclusion, the compounds β-caryophyllene, cinnamaldehyde, 2-methoxy cinnamaldehyde, benzyl benzoate and furfural may be promising as leads in the development of anti-inflammatory treatments in diseases of pathological inflammation, including AD
