Inhibition of ASC enhances the protective role of salvianolic acid A in traumatic brain injury via inhibition of inflammation and recovery of mitochondrial function

Folia Neuropathol. 2021;59(1):50-66. doi: 10.5114/fn.2021.105131.

Abstract

More than 50 million people are affected by traumatic brain injury (TBI) each year around the world, and nearly half of the population worldwide will have one or more TBI(s) in their lifetime. And in 2017, more than 1.39 billion people in China suffered from TBI, representing nearly 18% of the world population; these were mainly caused by road traffic incidents. Salvianolic acid A is a compound obtained from Salvia miltiorrhiza Bunge, which is one of the active components of many traditional Chinese medicines for the treatment of cardiovascular and cerebrovascular disease, with the effect of inhibition of inflammatory response. ASC is a critical factor in the activation of inflammation response process via promoting the maturation of caspase-1, and activation of NLPR3 under bacterial infection promotes the necrosis of cells in an ASC-dependent manner. However, few studies focus on the effect of ASC in a TBI model. In this study, we found that inhibition of ASC reduced the expression of inflammatory cytokines, and the concentration of calcium and ROS, while it increased the expression of mitochondrial function-related proteins. We further noticed that these effects were regulated by DLK2/MLK3/JNK signalling pathway and might contribute to the treatment of TBI.

Keywords: inflammation; mitochondria; salvianolic acid A; signalling pathway.; traumatic brain injury; ASC.

MeSH terms

  • Abietanes / pharmacology
  • Animals
  • Brain Injuries, Traumatic / drug therapy*
  • Brain Injuries, Traumatic / pathology
  • CARD Signaling Adaptor Proteins / antagonists & inhibitors*
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / metabolism
  • Caffeic Acids / pharmacology*
  • Caffeic Acids / therapeutic use*
  • Calcium / metabolism
  • Cell Line
  • Cell Proliferation
  • Cytokines / drug effects
  • Cytokines / metabolism
  • HEK293 Cells
  • Humans
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Lactates / pharmacology*
  • Lactates / therapeutic use*
  • Male
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / genetics

Substances

  • Abietanes
  • CARD Signaling Adaptor Proteins
  • Caffeic Acids
  • Cytokines
  • Lactates
  • Neuroprotective Agents
  • PYCARD protein, human
  • Pycard protein, mouse
  • Reactive Oxygen Species
  • tanshinone
  • salvianolic acid A
  • Calcium