Biomol Ther.  2013 Sep;21(5):332-337.

Kalopanaxsaponin A Exerts Anti-Inflammatory Effects in Lipopolysaccharide-Stimulated Microglia via Inhibition of JNK and NF-kappaB/AP-1 Pathways

• Jeong YH
• Hyun JW
• Kim Van Le T
• Kim DH
• Kim HS

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)-alpha expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-inflammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-kappaB and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation 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-kappaB/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.

Keyword

Microglia; Kalopanaxsaponin A; Anti-inflammation; JNK; NF-kappaB; AP-1

MeSH Terms

Alzheimer Disease
Brain Diseases
Brain Ischemia
Cyclooxygenase 2
DNA
Gene Expression
Interleukins
Kalopanax
MAP Kinase Signaling System
Microglia*
Multiple Sclerosis
Nervous System Diseases
NF-kappa B
Nitric Oxide Synthase Type II
Phosphorylation
Phosphotransferases
Saponins
Transcription Factor AP-1
Tumor Necrosis Factor-alpha
Up-Regulation
Cyclooxygenase 2
DNA
Interleukins
NF-kappa B
Nitric Oxide Synthase Type II
Phosphotransferases
Saponins
Transcription Factor AP-1
Tumor Necrosis Factor-alpha