Neuroinflammation with prolonged microglial activation leads to increased levels of pro-inflammatory mediators and subsequently contributes to neuronal dysfunction and neuronal loss. Therefore, pharmacological suppression of neuroinflammation would theoretically slow the progression of neurodegenerative disease. In this study, we investigated the anti-inflammatory effects and possible mechanisms of isodojaponin D (19-hydroxy-1α,6-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide), a new diterpene isolated from Isodon japonicus against lipopolysaccharide(LPS)-induced microglial activation in BV2 cells. Results from RT-PCR and Western blot showed that pretreatment with isodojaponin D (5 and 10μg/ml) prior to treatment with LPS (1μg/ml) significantly decreased LPS-induced production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in a dose-dependent manner. In addition, LPS-induced pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, were also decreased by pretreatment with isodojaponin D. This effect was accompanied by a decrease in translocations of Nuclear Factor-KappaB (NF-κB) p50 and p65 from the cytoplasm to the nucleus and by a decrease in I kappaB (IκB) degradation. In addition, pretreatment with isodojaponin D significantly attenuated LPS-induced mitogen-activated protein kinase (MAPK) activation. Taken together, these results suggest that isodojaponin D suppressed LPS-induced microglial activation and production of pro-inflammatory mediators by inhibition of the NF-κB signaling pathway and phosphorylation of MAPKs. These results suggest that isodojaponin D could play a beneficial role in treatment of neurodegenerative disease.
Bibliographical noteFunding Information:
This Research was supported by a Korea Research Foundation Grant funded by the Korean Government (KRF-2008-313-E00488) to S.-Y. Park, and by the ACE program through the National Research Foundation of Korea (NRF) grant funded by the Korean Ministry of Education, Science and Technology (MEST) (No. 2009-009-1414).
- BV2 cells
- Isodojaponin D (19-hydroxy-1,6-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide)
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