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. 2009 Apr;12(2):345-50.
doi: 10.1089/jmf.2007.0660.

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

Affiliations

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

Sang Woon Chung et al. J Med Food. 2009 Apr.

Abstract

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.

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Conflict of interest statement

No competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
Chemical structure of (A) zingerone and (B) curcumin.
<b>FIG. 2.</b>
FIG. 2.
Modulation of PPAR activity by zingerone in YPEN-1 cells. Cells were grown to 50–60% confluence after transfection of a reporter plasmid. The cells were incubated in serum-free medium with zingerone and fibrate for 6 hours. Luc, luciferase; RLU, relative luminescence units. Statistical significance: ###P < .001 for 5 μM zingerone versus 10 μM zingerone; ***P < .001 compared to untreated with zingerone.
<b>FIG. 3.</b>
FIG. 3.
Effects of zingerone on renal expression and activity of PPARs in old male rats. Western blot analysis was performed to detect PPARα/β/γ protein levels in nuclear extract from young and old rats and old rats fed zingerone. Statistical significance: #P < .05, ###P < .001 versus young rats; *P < .05, **P < .01, ***P < .001 versus zingerone-untreated old rats.
<b>FIG. 4.</b>
FIG. 4.
Effect of zingerone on age-related PPAR DNA binding activity. Young rats (6 months old) and old rats (21 months old) were used. Zingerone (2 or 8 mg/kg/day) was administered to the old group for 10 days. BL, blank. Statistical significance: ##P < .01 versus young rats; **P < .01, ***P < .001 versus zingerone-untreated old rats.
<b>FIG. 5.</b>
FIG. 5.
Effect of zingerone on age-related nuclear HNF-4. Nuclear extracts were prepared from kidney of young and old rats and old rats fed zingerone. Western blot analysis was performed to detect HNF-4 protein levels. Statistical significance: ###P < .001 versus young rats; *P < .01 versus zingerone-untreated old rats.
<b>FIG. 6.</b>
FIG. 6.
Inhibition of NF-κB activity by zingerone in YPEN-1 cells. Cells were permanently transfected with an NF-κB-containing plasmid linked to the luciferase gene, and then cells were co-treated with t-BHP for 6 hours after preincubation with zingerone (20 μM) and fibrate (20 μM) for 2 hours. RLU, relative luminescence units. Statistical significance: ##P < .001 versus untreated transfection control; **P < .01 versus 100 μM t-BHP-treated group.

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