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Published on: December 9, 2018
Licorice-derived dehydroglyasperin C increases MKP-1 expression and suppresses inflammation-mediated
Jaekyoon Kim1, Jiyoung Kim, Jaesung Shim
1WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
Abstract:
Recent studies have demonstrated that microglial hyperactivation-mediated neuroinflammation is involved in the pathogenesis of several neurodegenerative diseases. Thus, inhibiting microglial production of the neurotoxic mediator tumor necrosis factor-α (TNF-α) is considered a promising strategy to protect against neurodegeneration. Here, we investigated the inhibitory effect of licorice-derived dehydroglyasperin C (DGC) on lipopolysaccharide (LPS)-induced TNF-α production and inflammation-mediated neurodegeneration. We found that DGC pre-treatment attenuated TNF-α production in response to LPS stimulation of BV-2 microglia. DGC pre-treatment attenuated LPS-induced inhibitor of κB-α (IκB-α) and p65 phosphorylation and decreased the DNA binding activity of nuclear factor-κB (NF-κB). DGC pre-treatment also inhibited LPS-mediated phosphorylation of p38 mitogen-activated protein kinases (MAPKs) and extracellular signal-regulated kinase (ERK). Interestingly, DGC treatment of BV-2 microglia significantly increased MAPK phosphatase 1 (MKP-1) mRNA and protein expression, which is a phosphatase of p38 MAPK and ERK, suggesting that the DGC-mediated increase in MKP-1 expression might inhibit LPS-induced MAPKs and NF-κB activation and further TNF-α production. We also found that LPS-mediated microglial neurotoxicity can be attenuated by DGC. The addition of conditioned media (CM) from DGC- and LPS-treated microglia to neurons helped maintain healthy cell body and neurite morphology and increased the number of microtubule-associated protein 2-positive cells and the level of synaptophysin compared to treatment with CM from LPS-treated microglia. Taken together, these data suggest that DGC isolated from licorice may inhibit microglia hyperactivation by increasing MKP-1 expression and acting as a potent anti-neurodegenerative agent.
Insights
Dehydroglyasperin C from licorice inhibits microglia activation and neuroinflammation by increasing MKP-1 expression. This compound shows potential as an anti-neurodegenerative agent, protecting neurons from inflammatory damage.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Microglial hyperactivation drives neuroinflammation in neurodegenerative diseases.
- Inhibiting tumor necrosis factor-α (TNF-α) production by microglia is a key therapeutic strategy.
- Licorice-derived compounds are explored for their medicinal properties.
Purpose of the Study:
- To investigate the inhibitory effects of dehydroglyasperin C (DGC) on lipopolysaccharide (LPS)-induced microglial activation and neuroinflammation.
- To elucidate the molecular mechanisms underlying DGC's anti-neuroinflammatory actions.
- To evaluate DGC's neuroprotective potential against inflammation-mediated neurodegeneration.
Main Methods:
- BV-2 microglia were stimulated with LPS to induce inflammation.
- DGC pre-treatment was used to assess its inhibitory effects on TNF-α production and signaling pathways.
- Western blotting and RT-qPCR were employed to measure protein and mRNA expression (e.g., IκB-α, p65, MAPKs, MKP-1).
- NF-κB DNA binding activity was assessed.
- Conditioned media from treated microglia were applied to primary neurons to evaluate neuroprotection.
Main Results:
- DGC pre-treatment significantly attenuated LPS-induced TNF-α production in BV-2 microglia.
- DGC inhibited the activation of NF-κB and MAPK signaling pathways (p38 and ERK).
- DGC treatment increased the expression of MAPK phosphatase 1 (MKP-1), a negative regulator of MAPKs.
- DGC-treated microglia conditioned media protected neurons, preserving cell morphology and synaptic markers.
Conclusions:
- Dehydroglyasperin C effectively inhibits LPS-induced microglial hyperactivation and neuroinflammation.
- DGC's mechanism involves the upregulation of MKP-1, leading to the suppression of MAPK and NF-κB signaling.
- DGC demonstrates significant neuroprotective properties, suggesting its potential as a therapeutic agent for neurodegenerative diseases.