Kalopanaxsaponin A exerts anti-inflammatory effects in lipopolysaccharide-stimulated microglia via inhibition of JNK and NF-κB/AP-1 pathways

Yeon Hui Jeong, Jin Won Hyun, Tien Kim Van Le, Dong Hyun Kim, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Microglial activation plays an important role in the development and progression of various neurological disorders such as cerebral ischemia, multiple sclerosis, and Alzheimer's disease. Thus, controlling microglial activation can serve as a promising therapeutic strategy for such brain diseases. In the present study, we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-inflammatory cy-tokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-κB and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with up regulation of anti-inflammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinflammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-inflammatory effects of kalopanaxsaponin A in LPS-stimulated microglia.

Original languageEnglish
Pages (from-to)332-337
Number of pages6
JournalBiomolecules and Therapeutics
Volume21
Issue number5
DOIs
StatePublished - 2013

Keywords

  • AP-1
  • Anti-inflammation
  • JNK
  • Kalopanaxsaponin A
  • Microglia
  • NF-κB

Fingerprint

Dive into the research topics of 'Kalopanaxsaponin A exerts anti-inflammatory effects in lipopolysaccharide-stimulated microglia via inhibition of JNK and NF-κB/AP-1 pathways'. Together they form a unique fingerprint.

Cite this