Gypenoside XLIX alleviates sepsis-associated encephalopathy by targeting PPAR-α

Exp Neurol. 2025 Jan:383:115027. doi: 10.1016/j.expneurol.2024.115027. Epub 2024 Oct 28.

Abstract

Sepsis-related systemic inflammation is a deadly condition with high rates of morbidity and mortality. There is evidence that sepsis affects the brain, and the most frequent organ dysfunction linked to sepsis is sepsis-associated encephalopathy. Sepsis-related brain damage can drastically reduce a patient's chances of survival. However, a specific treatment for sepsis-associated encephalopathy is not currently available. Consequently, to treat the brain damage caused by sepsis, investigating novel therapeutic strategies is imperative. After establishing the CLP-induced mouse SAE model, we treated the mice with Gyp-XLIX and evaluated apoptosis, neuroinflammation, brain damage, and oxidative stress in the brain tissue of each group of mice. Furthermore, the protective effects of Gyp-XLIX on LPS-treated BV-2 cells were assessed. We discovered that Gyp-XLIX treatment increased the survival rate of CLP-treated mice, alleviated SAE-related cerebral nerve abnormalities, and decreased blood-brain barrier breakdown, all of which could better preserve brain tissue in vivo. Furthermore, we identified associated proteins and found that Gyp-XLIX may reduce oxidative stress, cell apoptosis, and inflammation in the brain tissues of SAE mice. This observation was further validated in vitro. We established that Gyp-XLIX alleviates SAE by targeting PPAR-α. These findings may be important for the clinical applicability of Gyp-XLIX in SAE treatment. We found that Gyp-XLIX can alleviate brain injury in SAE by targeting PPAR-α and is a potential protective agent for SAE.

Keywords: Apoptosis; Brain; Inflammation; Oxidative stress; PPAR-α; Sepsis.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Gynostemma
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • PPAR alpha* / metabolism
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Sepsis-Associated Encephalopathy* / drug therapy

Substances

  • PPAR alpha
  • gypenoside
  • Plant Extracts
  • Neuroprotective Agents
  • Ppara protein, mouse