טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentZagury Yedidya
SubjectBeta-Lactoglobulin Delivery System for Enhancing the
Bioaccessibility, Bioavailability and Biological
Efficacy of EGCG
DepartmentDepartment of Nanoscience and Nanotechnology
Supervisor Professor Yoav Livney
Full Thesis textFull thesis text - English Version


Abstract

(-)-Epigallocatechin-3-gallate (EGCG), the most prevalent catechin polyphenol in green tea, is a highly potent antioxidant. EGCG has received considerable attention due to its great health benefits, such as promoting the prevention of cardiovascular diseases, obesity, diabetes, cancer and neurodegenerative diseases. However, EGCG is highly susceptible to oxidation, it has a bitter and astringent taste and it has low bioavailability. To achieve maximal therapeutic utility of EGCG, a novel technology of food-grade beta lactoglobulin (β-Lg)-based delivery system had been developed in a previous study of our group. These EGCG-β-Lg complexes were found to protect EGCG during shelf life, and to mask its bitterness and astringency. In the current research, we explored the effect of complexation with β-Lg on EGCG stability and antioxidative activity mechanisms during simulated gastrointestinal digestion. The antioxidant activity was evaluated by ‘ferric reducing ability of plasma’ (FRAP) and by ‘oxygen radical absorbance capacity’ (ORAC) assays. β-Lg−complexed EGCG showed significantly greater stability and antioxidant activity, in both FRAP and ORAC assays, during simulated digestion, than free EGCG. We further evaluated the impact of complexation of EGCG with β-Lg on the bioaccessibility of EGCG in vitro, during simulated digestion and on the bioavailability of EGCG in vivo, in a rat model. The digested EGCG-β-Lg system exhibited significantly higher EGCG bioaccessibility compared to EGCG alone. Oral administration of 150 mg/kg EGCG complexed with β-Lg to male Sprague-Dawley rats significantly increased the plasma Cmax and area under the curve (AUC) by 2-fold compared to rats administered free EGCG. Additionally, the effect of EGCG-β-Lg delivery system on the efficacy of EGCG in the prevention of weight gain and impaired glucose homeostasis in a high fat diet (HFD)-induced obesity mice model was assessed. Metabolic effects were evaluated in mice fed either HFD or normal diet (ND), which concomitantly consumed either milk (1% fat) fortified with EGCG-β-Lg complexes, or free EGCG, or water with EGCG or water only, for 12 weeks. Weight gain and body fat percentage did not significantly differ between mice given milk enriched by EGCG-β-Lg complexes, and mice given milk enriched with free EGCG within each diet. However, HFD mice that received EGCG-β-Lg complexes in milk, had significantly lower liver-triglycerides levels compared to the control (HFD-water) group. Moreover, EGCG-β-Lg complexes in milk significantly reduced the glycemic response, in both diets (more markedly in ND) compared to free EGCG in milk. A tendency toward improved insulin sensitivity was observed in mice fed with β-Lg-complexed EGCG compared to free EGCG in milk. Thus, β-Lg delivery system has the potential to improve the efficacy of polyphenols like EGCG in preventing metabolic syndrome effects.