Kalopanaxsaponin A Exerts Anti-Inflammatory Effects in Lipopolysaccharide-Stimulated Microglia via Inhibition of JNK and NF-κB/AP-1 Pathways
| Autor: | Yeon Hui Jeong, Dong-Hyun Kim, Tien Kim Van Le, Jin Won Hyun, Hee Sun Kim |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharide
medicine.medical_treatment Pharmacology Biochemistry NF-κB Proinflammatory cytokine chemistry.chemical_compound Anti-inflammation Drug Discovery medicine Microglia biology business.industry Articles AP-1 NFKB1 Nitric oxide synthase medicine.anatomical_structure Cytokine chemistry Immunology biology.protein Molecular Medicine Kalopanaxsaponin A Tumor necrosis factor alpha JNK business |
| Zdroj: | Biomolecules & Therapeutics |
| ISSN: | 1976-9148 |
| Popis: | 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 cytokine 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 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-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. |
| Databáze: | OpenAIRE |
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