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.

Brain Research
|June 8, 2025
PubMed
Abstract

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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