Phytochemicals as Modulators of PPARs and RXRs

Welcome to this special issue of PPAR Research on " Phyto-chemicals as modulators of PPARs and RXRs. " Plants have played a crucial role in the prevention and treatment of human diseases for thousands of years. A significant number of contemporary drugs with high efficacy are derived from herbal origin. These natural phytochemicals, including certain nutrients, are therefore of great medicinal value. Peroxisome proliferator-activated receptors (PPARs) belong to the steroid hormone receptor superfamily that bind to and are activated by fatty acids, eicosanoids, and a group of xenobiotics called peroxisome proliferators. Each of these receptors binds to specific peroxisome proliferator response elements (PPRE) as a heterodimer with a retinoid X receptor (RXR). Binding to these receptors has been proven to control the pathological conditions associated with obesity , aging-related diseases, inflammation, immune disorder, cell cycle regulation as well as cancer. There is a strong mech-anistic basis for PPAR and RXR targeting, as these nuclear receptors are transcriptional factors that modulate gene expression relevant to the control of blood glucose and lipids, as well as the processes of inflammation and carcinogenesis. Since PPARs play an important role in lipid metabolism, the search for natural ligands had begun with fatty acids and eicosanoids. In fact, the discovery that many natural dietary compounds, especially phytochemicals, are PPAR activators is of great significance for human health. With metabolic syndrome, diabetes, and chronic systemic inflammatory diseases now reaching pandemic proportions, the importance of the discovery of natural PPAR ligands is self-evident. The special issue begins with a review of terpenoids as modulators of the PPAR family. To date more than 40,000 terpenoids have been described. Also known as isoprenoids, terpenoids constitute one of the largest and most diverse group of phytochemicals. Members of this phytochemical family are well known to us as the flavours of cinnamon, ginger , and cloves and the scents of camphor and eucalyptus. The vitamin A precursors known as carotenoids and psyc-hoactive cannabinoids are also forms of terpenoid. In this issue, T. Goto and colleagues review the biosynthesis, metabolism , and plant origins of various dietary terpenoids. The physiological effects of these compounds on carbohydrate and lipid metabolism are described in terms of their PPARγ and PPARα activating abilities. This is followed by the research article on the kinetic assessment and therapeutic modulation of metabolic and obesity-associated inflamma-tory profiles by a high-fat diet, whereas the whole process was found to be …