PPARγ activation by baicalin suppresses NF-κB-mediated inflammation in aged rat kidney

Baicalin, a herb-derived flavonoid compound, has beneficial activities, including the modulation of oxidative stress and inflammation. Nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a ligand-activated transcription factor that plays an important role in regulating nuclear factor-kappa B (NF-kappa B)-induced age-related inflammation. We investigated the anti-inflammatory action of baicalin, which depends on its ability to activate PPAR gamma, and subsequently to suppress NF-kappa B. We examined baicalin-treated kidney tissue from 24-month-old Fischer 344 aged rats (10 or 20 mg/kg/day for 10 days) and baicalin-fed mice (10 mg/kg/day for 3 days) for in vivo investigations, and used endothelial YPEN-1 cells for in vitro studies. In the baicalin-fed aged rats, there was a marked enhancement of both nuclear protein levels and DNA binding activity of PPAR gamma, and a decreased expression of NF-kappa B target genes (VCAM-1, IL-1 beta, and IL-6) compared with non-baicalin-fed aged rats. Furthermore, to confirm the anti-inflammatory action of PPAR gamma activated by baicalin, we used lipopolysaccharide (LPS)-treated cells and mice. The results showed that baicalin induced PPAR gamma-selective activation in YPEN-1 cells, and that the effects of baicalin were blocked by the PPAR gamma receptor antagonist, GW9662. In addition, baicalin treatment prevented RS generation, NF-kappa B activation and the expression of pro-inflammatory genes, whereas it increased PPAR gamma expression in LPS-treated cells and mouse kidney. Our data suggest that baicalin-induced PPAR gamma expression reduced age-related inflammation through blocking pro-inflammatory NF-kappa B activation. These results indicate that baicalin is a novel PPAR gamma activator and that this agent may have the potential to minimize inflammation.