Punicalagin Decreases Serum Glucose Levels and Increases PON1 Activity and HDL Anti‐Inflammatory Values in Balb/c Mice Fed a High‐Fat Diet

Polyphenols are consumed daily in the human diet and are associated with reduced risk of a number of chronic diseases, including cancer, cardiovascular disease, and diabetes. Traditionally, the health benefits of polyphenols have been attributed to their antioxidant activity, but many studies might be hampered by oral administration and insignificant bioavailability. Rather than exerting a direct antioxidant effect, the mechanisms by which polyphenols express their beneficial effect seem to involve their interaction with proteins. The present study is aimed at broadening and confirming our recently published in vitro results showing that polyphenols may reduce atherosclerosis risk via interaction with proteins and lipoproteins related to atherosclerosis. The biological functions of punicalagin and quercetin in relation to glucose and lipid levels, paraoxonase 1 (PON1) activity, and inflammation were examined in vivo. Mice were fed a high-fat diet (HFD) for 12 weeks, and during the last 4 weeks, they received subcutaneous treatments via implanted minipumps, which released physiological concentrations of punicalagin, quercetin, or atorvastatin (as a positive control) daily into the serum. The HFD reduced serum PON1 activity, whereas punicalagin administration restored PON1 activity to the level of mice fed a normal diet. In addition, punicalagin significantly reduced glucose levels in HFD mice and improved HDL anti-inflammatory properties. In conclusion, beyond antioxidant activity, the mechanisms by which polyphenols exert their beneficial properties appear to involve their interaction with serum proteins that mediate HDL function and lipid-glucose state in the circulation.