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-γ (PPARγ) is a ligand-activated transcription factor that plays an important role in regulating nuclear factor-κB (NF-κB)-induced age-related inflammation. We investigated the anti-inflammatory action of baicalin, which depends on its ability to activate PPARγ, and subsequently to suppress NF-κB. 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 PPARγ, and a decreased expression of NF-κB target genes (VCAM-1, IL-1β, and IL-6) compared with non-baicalin-fed aged rats. Furthermore, to confirm the anti-inflammatory action of PPARγ activated by baicalin, we used lipopolysaccharide (LPS)-treated cells and mice. The results showed that baicalin induced PPARγ-selective activation in YPEN-1 cells, and that the effects of baicalin were blocked by the PPARγ receptor antagonist, GW9662. In addition, baicalin treatment prevented RS generation, NF-κB activation and the expression of pro-inflammatory genes, whereas it increased PPARγ expression in LPS-treated cells and mouse kidney. Our data suggest that baicalin-induced PPARγ expression reduced age-related inflammation through blocking pro-inflammatory NF-κB activation. These results indicate that baicalin is a novel PPARγ activator and that this agent may have the potential to minimize inflammation.
Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Gumjung-gu, Busan, Republic of Korea.
Hyun Ae
HA
Lim
Eun Kyeong
EK
Lee
Ji Min
JM
Kim
Min Hi
MH
Park
Dae Hyun
DH
Kim
Yeon Ja
YJ
Choi
Young Mi
YM
Ha
Jeong-Hyun
JH
Yoon
Jae Sue
JS
Choi
Byung Pal
BP
Yu
Hae Young
HY
Chung
D000367:Age Factors; D000375:Aging / Q000276:immunology / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009393:Nephritis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014162:Transfection; D015854:Up-Regulation
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D005419:Flavonoids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; C440499:lipopolysaccharide, Escherichia coli O111 B4; C038044:baicalin