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Use of Phytochemicals against Neuroinflammation
WeiāYi Ong,1,2 Tahira Farooqui,3 Christabel FungāYih Ho,1 YeeāKong Ng,1 and Akhlaq A. Farooqui 4
1 Department of Anatomy, National University of Singapore, Singapore
2 Neurobiology and Ageing Research Programme, National University of Singapore, Singapore
3 Department of Entomology, Ohio State University, Columbus, OH, USA
4 Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH, USA
1.1 Introduction
Neuroinflammation and oxidative stress are closely associated with the pathogenesis of neurotraumatic and neurodegenerative diseases, such as stroke and Alzheimerās disease (AD). During the inflammatory reaction, secretion of proinflammatory cytokines and chemokines amplifies and maintains inflammatory responses. It involves the enzymatic activity of cytosolic phospholipase A2 (cPLA2) and secretory phospholipase A2 (sPLA2), which release arachidonic acid from glycerophospholipids, and of cyclooxygenase (COX) and 5ālipoxygenase (5āLOX), which oxidize arachidonic acid to proinflammatory eicosanoids. This is followed by the formation of the prostaglandin D2 (PGD2) and of docosahexaenoic acid (DHA)āderived resolvins and protectins, which facilitate the resolution of inflammation. Acute neuroinflammation is a protective process that isolates the injured brain tissue from uninjured areas, destroys injured cells, and rebuilds the extracellular matrix. Without it, brain tissue would rapidly be damaged by the effects of injury and infections, including those of microbial, viral, and prion origin. Acute neuroinflammation involves the recruitment of lymphocytes, monocytes, and macrophages of the hematopoietic system and glial cells of the central nervous system (CNS). Microglia are recruited to the site of injury to protect and repair the injured tissue via the secretion of cytokines, chemokines, and lipid mediators such as resolvins and neuroprotectins, while astrocytes react by forming a glial scar. Chronic neuroinflammation, on the other hand, lingers for years, and causes damage to brain tissues. It is closely associated with the activity of microglia and astrocytes and with the assembly and activation of the inflammasome: a multiprotein oligomer consisting of caspase 1, PYCARD, NALP, and sometimes caspase 5 (also known as caspase 11 or ICHā3). Once activated, the inflammasome binds to and appositions together many p45 proācaspaseā1 molecules to induce their autocatalytic cleavage to p20 and p10 subunits. Caspaseā1 then assembles into its active form (consisting of two heterodimers with a p20 and p10 subunit each), in order to carry out a variety of processes, including cleavage of proāinterleukin (IL)ā1Ī² into ILā1Ī², cleavage of proāILā18 into ILā18 to induce interferon gamma (IFNāĪ³) secretion, and activation of lipid biosynthesis [1]. Inflammasomes orchestrate the activation of precursors of proinflammatory caspases, which, in turn, cleave precursor forms of ILā1Ī², ILā18, and ILā33 into their active forms. These lead to further stimulation of PLA2, COXā2, and LOX; generation of eicosanoids, lysophosphatidylcholine (lysoāPtdCho), and plateletāactivating factor (PAF); production of reactive oxygen species (ROS), proteinases, and complement proteins; and a potent inflammatory response. Alterations in the expression of inflammasome mediators may lead to neurodegeneration in neurotraumatic, neurodegenerative, and neuropsychiatric diseases. Based on this, it has been suggested that regulation of the inflammasome machinery may be better than suppression of all inflammation for the treatment of inflammatory conditions [1,2].
An emerging approach to the alleviation of neuroinflammation involves the use of medicinal plants and herbs. Epidemiological studies have indicated that the incidence of neurological disorders among people living in Asia is lower than that in the Western world. This may be due to the regular consumption of phytochemicals in the form of spices. Extensive research over the last 10 years has indicated that phytochemicals derived from various spices e.g., turmeric, red pepper, black pepper, licorice, clove, ginger, garlic, coriander, cinnamon, target inflammatory and oxidative stress pathways and retard or delay the onset of neurological diseases. More than 7000 phytochemicals, which possess antiproliferative, antiāinflammatory, antiviral, and hypocholesterolemic properties, have been identified (Figure 1.1). Unlike vitamins and minerals, phytochemicals are not required for the maintenance of cell viability, but play a vital role in protecting neural cells from neuroinflammation and oxidative stress associated with aging and brain disea...
