2. Academic Validation
  3. Gypenoside XLIX alleviates sepsis-associated encephalopathy by targeting PPAR-α

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

  • Exp Neurol. 2025 Jan:383:115027. doi: 10.1016/j.expneurol.2024.115027.
Panpan Zhao 1,  Wei Zhang 2,  Xinyu Zhou 3,  Yikun Zhao 1,  Aimin Li 4,  Yong Sun 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Institute of Neuroscience, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang 222000, China.
  • 2 Department of Neurosurgery, Institute of Neuroscience, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang 222000, China; Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China.
  • 3 Department of Neurology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang 222000, China.
  • 4 Department of Neurosurgery, Institute of Neuroscience, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang 222000, China. Electronic address: [email protected].
  • 5 Department of Neurosurgery, Institute of Neuroscience, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang 222000, China. Electronic address: [email protected].
PMID: 39490624 DOI: 10.1016/j.expneurol.2024.115027
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.

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