Raddeanin A (RA) reduced acute inflammatory injury in mouse experimental cerebral hemorrhage by suppression of TLR4

Int J Med Sci. 2022 Jul 11;19(8):1235-1240. doi: 10.7150/ijms.73007. eCollection 2022.

Abstract

Spontaneous intracerebral hemorrhage (ICH) is associated with high mortality and disability rates. The microglia-induced inflammatory response is a critical factor determining brain tissue damage after ICH. Raddeanin A (RA) is a natural triterpenoid compound with anti-inflammatory effects, although its effects on ICH and the underlying molecular mechanism have not been elucidated. In this study, we found that RA reduced the volume of cerebral hematoma and cerebral edema, attenuated neuronal apoptosis and improved the behavioral indices in a murine model of acute cerebral hemorrhage. Mechanistically, RA downregulated the TLR4-mediated pro-inflammatory effectors, reduced infiltration of microglia in peri-intracerebral hemorrhage and inhibited apoptosis of neurons co-cultured with activated microglia. In conclusion, RA can alleviate ICH-related tissue damage and promote the recovery of neuronal function by suppressing microglia-induced inflammation and apoptosis.

Keywords: Intracerebral hemorrhage; Raddeanin A; TLR4; inflammation; microglia.

MeSH terms

  • Animals
  • Brain Edema* / complications
  • Brain Edema* / etiology
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / drug therapy
  • Mice
  • Microglia
  • Saponins
  • Toll-Like Receptor 4*

Substances

  • Saponins
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • raddeanin A