Abstract

Metabolic syndrome, characterized by obesity, hypertension, high blood glucose and triglyceride, increases the risk for heart disease, stroke and diabetes. Inflammation and oxidative stress have been linked to the development of many disorders associated with aging such as tissue damage and neurodegeneration. More recently, metabolic diseases such as Type II diabetes, metabolic syndrome, lipid disorders and obesity have been associated with oxidative stress and believed to have inflammatory components. As part of inflammatory pathway, activation of NF-κB leads to insulin resistance and by blocking this pathway, insulin resistance and the resultant Type II diabetes can be prevented. Inducible nitric oxide synthase plays a key role in the process of inflammation and considered as a potential target for inflammation. Overproduction of nitric oxide in response to endotoxins and proinflammatory mediators has been implicated in various pathological processes. Oxidative stress due to excessive generation of intracellular reactive oxygen species is linked to degenerative conditions such as cardiovascular disease, inflammation, Alzheimer's and Parkinson's diseases, diabetes, and aging. The peroxisome proliferator-activated receptor (PPAR) isoforms are members of the nuclear receptor superfamily of ligand-activated transcription factors. They play a central role in carbohydrate and lipid metabolism and also regulate energy metabolism, cell proliferation and inflammation. Activators of PPARα and PPARγ are effective in lowering blood sugar and lipids. PPARα activators are useful in the treatment of cardiovascular disease and diabetes due to their lipid lowering action and improving insulin sensitivity without adipocyte differentiation. PPARγ activation regulates adipocyte differentiation and glucose homeostasis. PPARs are important targets to treat metabolic disorders and PPAR ligands are emerging as important class of therapeutic agents. As part of our ongoing program to study medicinal plants, a battery of target based cellular assays is utilized to screen the anti-inflammatory, antioxidant and PPAR activation properties of plants extracts and isolated constituents and their potential to be used in conditions of diabetes, metabolic syndrome and cardiovascular disease.

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