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Updated: Jun 12, 2026

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
The new diterpene isodojaponin D inhibited LPS-induced microglial activation through NF-kappaB and MAPK signaling
Ji-Youn Lim1, Tae Joon Won, Bang Yeon Hwang
1Graduate School of Medicine, Korea University, Seoul 136-701, Republic of Korea.
Abstract:
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-1alpha,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 10 microg/ml) prior to treatment with LPS (1 microg/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-1beta, IL-6, and TNF-alpha, were also decreased by pretreatment with isodojaponin D. This effect was accompanied by a decrease in translocations of Nuclear Factor-KappaB (NF-kappaB) p50 and p65 from the cytoplasm to the nucleus and by a decrease in I kappaB (IkappaB) 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-kappaB signaling pathway and phosphorylation of MAPKs. These results suggest that isodojaponin D could play a beneficial role in treatment of neurodegenerative disease.
Insights
Isodojaponin D, a diterpene from Isodon japonicus, reduces neuroinflammation by inhibiting microglial activation. This compound suppressed pro-inflammatory mediators via the NF-kappaB and MAPK pathways, offering potential for neurodegenerative disease treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Neuroinflammation, driven by microglial activation, elevates pro-inflammatory mediators, leading to neuronal damage.
- Suppression of neuroinflammation is a potential therapeutic strategy for neurodegenerative diseases.
Purpose of the Study:
- To investigate the anti-inflammatory effects of isodojaponin D on lipopolysaccharide (LPS)-induced microglial activation.
- To elucidate the underlying mechanisms of isodojaponin D's anti-inflammatory action.
Main Methods:
- BV2 microglial cells were treated with isodojaponin D prior to LPS stimulation.
- RT-PCR and Western blot analyses were used to assess the expression of inflammatory markers.
- NF-kappaB and MAPK signaling pathways were investigated.
Main Results:
- Isodojaponin D significantly reduced LPS-induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) production in a dose-dependent manner.
- Pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) were decreased by isodojaponin D.
- Inhibition of NF-kappaB (p50, p65) nuclear translocation and IkappaB degradation, along with attenuated MAPK activation, was observed.
Conclusions:
- Isodojaponin D suppresses LPS-induced microglial activation and pro-inflammatory mediator production.
- The anti-inflammatory effects are mediated through the inhibition of NF-kappaB signaling and MAPK phosphorylation.
- Isodojaponin D shows promise as a therapeutic agent for neurodegenerative diseases.
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