Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Kalopanaxsaponin A Exerts Anti-Inflammatory Effects in Lipopolysaccharide-Stimulated Microglia via Inhibition of JNK and NF-κB/AP-1 Pathways

  • Jeong, Yeon-Hui (Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School) ;
  • Hyun, Jin-Won (Department of Biochemistry, College of Medicine, Cheju National University) ;
  • Le, Tien Kim Van (Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University) ;
  • Kim, Dong-Hyun (Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University) ;
  • Kim, Hee-Sun (Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School)
  • Received : 2013.09.04
  • Accepted : 2013.09.23
  • Published : 2013.09.30
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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-${\kappa}B$ 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-${\kappa}B$/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.

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References

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