Investigation of anti-inflammatory compounds from food and plant libraries for use in Alzheimer's disease

Shanmugam, Kirubakaran (2011) Investigation of anti-inflammatory compounds from food and plant libraries for use in Alzheimer's disease. PhD thesis, James Cook University.

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Abstract

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.

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.

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.

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.

Item ID: 40065
Item Type: Thesis (PhD)
Keywords: ageing; age-related; alternative medicine; Alzheimer's disease; Alzheimer's; anti-inflammatory; basic pharmacology; biologically active molecules; Chinese medicine; Chinese traditional medicine; Commonwealth Scientific and Industrial Research Organisation; complementary medicine; CSIRO; diet therapy; food and plant; food; inflammation; mental health; microglia; mushrooms; natural medicines; natural products; neurodegenerative disorders; plant products; plants; preventative medicine
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Publications arising from this thesis are available from the Related URLs field. The publications are:

Ravipati, Anjaneya S., Zhang, Lin, Koyyalamudi, Sundar Rao, Jeong, Sang Chul, Reddy, Narsimha, Bartlett, John, Smith, Paul T., Shanmugam, Kirubakaran, Münch, Gerald, Wu, Ming Jie, Satyanarayanan, Manavalan, and Vysetti, Balaram (2012) Antioxidant and anti-inflammatory activities of selected Chinese medicinal plants and their relation with antioxidant content. BMC Complementary and Alternative Medicine, 12. pp. 1-14.

Zhang, Lin, Ravipati, Anjaneya S., Koyyalamudi, Sundar Rao, Jeong, Sang Chul, Reddy, Narsimha, Smith, Paul T., Bartlett, John, Shanmugam, Kirubakaran, Münch, Gerald, and Wu, Ming Jie (2011) Antioxidant and anti-inflammatory activities of selected medicinal plants containing phenolic and flavonoid compounds. Journal of Agricultural and Food Chemistry, 59 (23). pp. 12361-12367.

Berbaum, Katrin, Shanmugam, Kirubakaran, Stuchbury, Grant, Wiede, Florian, Körner, Heinrich, and Münch, Gerald (2008) Induction of novel cytokines and chemokines by advanced glycation endproducts determined with a cytometric bead array. Cytokine, 41 (3). pp. 198-203.

Maczurek, Annette, Shanmugam, Kirubakaran, and Münch, Gerald (2008) Inflammation and the redox-sensitive AGE-RAGE pathway as a therapeutic target in Alzheimer's disease. Annals of the New York Academy of Sciences, 1126. pp. 147-151.

Date Deposited: 03 Sep 2015 04:05
FoR Codes: 03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030401 Biologically Active Molecules @ 33%
11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology @ 33%
11 MEDICAL AND HEALTH SCIENCES > 1104 Complementary and Alternative Medicine > 110499 Complementary and Alternative Medicine not elsewhere classified @ 34%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920112 Neurodegenerative Disorders Related to Ageing @ 33%
92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920412 Preventive Medicine @ 33%
92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920410 Mental Health @ 34%
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