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Updated: Jun 15, 2025

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Ononin modulates SIRT2-mediated glycolysis and inflammation in LPS-activated microglia via PKM2 deacetylation
Qunshan Chen1, Weixian Xu2, Xiaofang Tong3
1Pain Management Centre, Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, HangZhou, China.
Background:
Inhibition of inflammation and glycolysis of microglia contributes to neuropathic pain treatment. Ononin, a compound isolated from various plants, has been found to have various anti-inflammatory and anti-tumor effects.
Aim:
To investigate the therapeutic potential and mechanism of Ononin on microglial activation.
Methods:
BV2 microglial cells were treated with LPS to mimic microenvironment of neuropathic pain in vitro, and gene expression was analyzed by qPCR array analysis after Ononin treatment. The effects of Ononin and SIRT2 gene on inflammation and glycolysis were then investigated. PKM2 acetylation sites were predicted using the GPS-PAL database. The interaction between PKM2 and SIRT2 protein was also studied.
Results:
Ononin at 40 μM significantly inhibited inflammation and glycolysis in LPS-treated BV2 microglial cells, and this was related to the upregulation of SIRT2 levels. Inhibition of SIRT2 weakened the regulatory effects of Ononin, and induced PKM2 acetylation to enhance glycolysis in BV2 cells. SIRT2 exerts deacetylation modification at K207 site of PKM2 protein to reduce the stability of PKM2 protein.
Conclusions:
SIRT2-mediated metabolic reprogramming and inflammation are critical for neuropathic pain, and Ononin shows therapeutic potential by modulating SIRT2 to suppress PKM2 protein stability in the deacetylation way, suggesting it as a promising treatment option.
Insights
Ononin, a plant compound, shows therapeutic potential for neuropathic pain by inhibiting microglial inflammation and glycolysis. It works by modulating SIRT2 to suppress PKM2 protein stability, offering a promising treatment option.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Microglial inflammation and glycolysis are key targets for neuropathic pain treatment.
- Ononin, a plant-derived compound, exhibits anti-inflammatory and anti-tumor properties.
Purpose of the Study:
- To explore the therapeutic potential of Ononin in treating neuropathic pain.
- To elucidate the mechanism of Ononin's action on microglial activation.
Main Methods:
- BV2 microglial cells were stimulated with LPS to model neuropathic pain conditions.
- Gene expression was analyzed using qPCR array after Ononin treatment.
- The roles of Ononin, SIRT2, and PKM2 acetylation in inflammation and glycolysis were investigated.
Main Results:
- Ononin (40 μM) significantly reduced inflammation and glycolysis in LPS-treated BV2 cells, correlating with increased SIRT2 levels.
- SIRT2 inhibition diminished Ononin's effects and promoted PKM2 acetylation, thereby enhancing glycolysis.
- SIRT2 deacetylated PKM2 at the K207 site, reducing PKM2 protein stability.
Conclusions:
- SIRT2-mediated metabolic reprogramming and inflammation are crucial in neuropathic pain.
- Ononin demonstrates therapeutic potential by utilizing SIRT2 to decrease PKM2 protein stability via deacetylation.
- Ononin represents a promising candidate for neuropathic pain treatment.
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