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

Affiliations
  • 1Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School, Seoul 158-710, Republic of Korea. hskimp@ewha.ac.kr
  • 2Department of Biochemistry, College of Medicine, Cheju National University, Jeju 690-756, Republic of Korea.
  • 3Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.

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
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