Peroxisome proliferator-activated receptor activation by a short-term feeding of zingerone in aged rats

Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptor family, are key regulators of various metabolic pathways related to lipid and glucose metabolism as well as inflammation. We examined the effect of zingerone, a major ingredient of ginger, on PPAR, hepatic nuclear factor-4 (HNF-4), and nuclear factor-kappaB (NF-kappaB) expression in 21-month-old male Sprague-Dawley rats. Two experimental groups receiving doses of either 2 or 8 mg/kg/day zingerone for 10 days were compared with young rats (6 months old) and an age-matched control group. For molecular work, the endothelial cell line YPEN-1 was used. Both the 2 and 8 mg/kg/day dose of zingerone significantly increased DNA binding activities of PPARs (2.8-fold). Expression of HNF-4 was also increased in the group receiving the 8 mg/kg/day dose. We further showed that zingerone partially prevented the age-related decline in PPAR expression. In vitro experiments revealed zingerone (10 microM) increased PPAR expression (2.5-fold) to a similar extent as the PPAR agonist fibrate (5 microM) and suppressed pro-inflammatory transcription factor NF-kappaB activity. Collectively, our findings suggest that zingerone exerts its potent anti-inflammatory action by increasing HNF-4 and PPAR activities, while suppressing NF-kappaB activity.