RESULTS: The mRNA expression of PPARα was significantly induced in HCT116 cells following treatment with chrysin for 36 h, but the mRNA expression of PPARα was inhibited, when the cells were treated with a combination of chrysin and MK886 (PPARα inhibitor). This phenomenon proved that the incorporation of MK886 lowers the expression levels of PPARα, thus enabling us to study the function of PPARα. The cell population of the G0/G1 phase significantly increased in chrysin-treated cells, which was accompanied by a decrease in the percentage of S phase cell population after 12 h of treatment. However, treatments of HCT116 cells with chrysin only or a combination of chrysin and MK886 did not show the opposite situation in the G0/G1 and S phase cell populations, indicating that the expression of PPARα may not be associated with the cell cycle in the treated cells. The migration rate in chrysin-treated HCT116 cells was reduced significantly after 24 and 36 h of treatments. However, the activity was revived, when the expression of PPARα was inhibited, indicating that the migration activity of chrysin-treated cells is likely correlated with the expression of PPARα. Comparison of the CYP2S1 and CYP1B1 mRNA expression in chrysin only treated, and a combination of chrysin and MK886-treated HCT116 cells for 24 and 36 h showed a significant difference in the expression levels, indicating that PPARα inhibitor could also modify the expression of CYP2S1 and CYP1B1.
CONCLUSION: The study indicates that PPARα may play an essential role in regulating the migration activity, and the expression of CYP2S1 and CYP1B1 in chrysin-treated colorectal cancer cells.
METHODS: HepG2 cells were treated with different concentrations of KMF and 0.5 mM palmitate (PA) for 24 h. The mRNA and protein levels of genes involved in lipid metabolism were evaluated using real-time PCR and western blot. The expression of Nrf2 was silenced using siRNA.
RESULTS: Data indicated that KMF (20 μM) reversed PA-induced increased triglyceride (TG) levels and total lipid content. These effects were accompanied by down-regulation of the mRNA and protein levels of lipogenic genes (FAS, ACC and SREBP1), and up-regulation of genes related to fatty acid oxidation (CPT-1, HADHα and PPARα). Kaempferol significantly decreased the levels of the oxidative stress markers (ROS and MDA) and enhanced the activities of antioxidant enzymes SOD and GPx in PA-challenged cells. Luciferase analysis showed that KMF increased the transactivation of Nrf2 in hepatocytes. The results also revealed that KMF-mediated activation of Nrf2 target genes was suppressed by Nrf2 siRNA. Furthermore, Nrf2 siRNA abolished the KMF-induced reduction in ROS and MDA levels in PA treated cells. In addition, the inhibitory effect of KMF on TG levels and the mRNA and protein levels of FAS, ACC and SREPB-1 were significantly abolished by Nrf2 inhibition. Nrf2 inhibition also suppressed the KMF-induced activation of genes involved in β oxidation (CPT-1 and PPAR-α).
CONCLUSION: The results suggest that KMF protects HepG2 cells from PA-induced lipid accumulation via activation of the Nrf2 signaling pathway.
RESULTS: Compared to the non-obese diabetic resistant (NOR) mice, the peritoneal macrophages of NOD mice expressed increased levels of PPARalpha but reduced levels of PPARgamma2, while PPARgamma1 expression was unchanged in all age groups. CD4-positive lymphocytes expressed low levels of PPARalpha in diabetic NOD mice and greatly reduced expression of PPARgamma2 in all age groups. Unlike peritoneal macrophages and CD4-positive cells, the CD8-positive cells expressed low levels of PPARgamma1 in diabetic NOD mice but no difference in PPARalpha and PPARgamma2 expression was observed compared to NOR mice.
CONCLUSION: The current findings may suggest an important regulatory role of PPARs in the pathogenesis of autoimmune diabetes.