EVALUATION OF IN VITRO ANTI-INFLAMMATORY, ANTI-DIABETIC AND ANTI-LIPOGENIC ACTIVITY OF NATURAL POLYPHENOLIC EXTRACTS AND THEIR PURE CONSTITUENTS

The long-term goals and objectives of our group are to identify bioactive natural products relevant to human disease prevention and health promotion. To attain this goal, the objective of this thesis was to demonstrate that bioactive polyphenol-rich extracts or preparations exert positive health benefits beyond basic nutrition, thus impacting overall health and wellness. We believe that this project has immense scientific merit from a human health perspective and will be of great public impact given that consumers are seeking natural and organic choices for improving health. In this investigation, we have focused our attention on investigating the biological activities of two novel phenolic-rich preparations derived from curcumin and maple syrup for future nutraceutical applications. The work herein assessed the anti-inflammatory properties of novel standardized curcumin formulation Longvida® and phenolic-enriched maple syrup extract using a well-known in vitro model of inflammation, lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages. RAW 264.7 cells were co-treated with 50 ng/mL LPS and test extracts for 24 hours and then inflammatory markers were measured using supernatants, gene and protein expression. The activation of nuclear factor-kappa B (NFκB) was measured using luciferase activity. Both polyphenolic extracts were able to alleviate the LPS stimulated inflammation by down-regulating the inflammatory markers via targeting nuclear factor-kappa B (NFκB) (a major pathway modulated in inflammation) transcriptional activity in murine macrophages. Next, the work herein studied the anti-hyperglycemic and anti-lipogenic properties of novel standardized nutraceutical grade phenolic rich extract, MSX. Human HepG2 cells were treated with the MSX for 24 h. Glucose consumption, AMP activated protein kinase (AMPK) activation and its target gluconeogenic gene expression were measured. The glucose levels were reduced by MSX in the hepatocytes though AMPK activation. Subsequently, the anti-lipogenic effect of MSX treatment in mature differentiated 3T3-L1 murine adipocytes and human visceral adipocytes was evaluated. MSX treatment to mature adipocytes decreased lipid accumulation compared to control in both murine and human adipocytes. In 3T3-L1 adipocytes, this effect was associated with downregulation of adipo/lipogenic protein expression (e.g. PPARγ, Srebp1c). We also observed reduced mRNA expression of the pro-inflammatory mediators, namely IL-6, and TNF-α. Taken together, we demonstrated that a novel maple syrup extract exhibited anti-inflammatory, anti-hyperglycemic and anti-lipogenic activities in vitro. The current study adds to the growing body of in vitro and in vivo data supporting the biological effects and potential health benefits of the novel curcumin formulation Longvida® and the natural sweetener, maple syrup