2. Academic Validation
  3. Gypenoside XLIX Activates the Sirt1/Nrf2 Signaling Pathway to Inhibit NLRP3 Inflammasome Activation to Alleviate Septic Acute Lung Injury

Gypenoside XLIX Activates the Sirt1/Nrf2 Signaling Pathway to Inhibit NLRP3 Inflammasome Activation to Alleviate Septic Acute Lung Injury

  • Inflammation. 2025 Feb;48(1):42-60. doi: 10.1007/s10753-024-02041-2.
Kaixin Ping # 1 2,  Rongrong Yang # 3,  Huizhen Chen # 2,  Shaocheng Xie 1,  Yannan Xiang 1 3,  Mengxin Li 1 2,  Yingzhi Lu 4,  Jingquan Dong 5
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang, 222005, China.
  • 2 Institute of Neuroscience, Neurosurgery Department, The First People's Hospital of Lianyungang, Lianyungang, 222005, China.
  • 3 Department of Oncology, The Second People's Hospital of Lianyungang (The Oncology Hospital of Lianyungang), Affiliated to Kangda College of Nanjing Medical University, Lianyungang, 222000, China.
  • 4 Department of Oncology, The Second People's Hospital of Lianyungang (The Oncology Hospital of Lianyungang), Affiliated to Kangda College of Nanjing Medical University, Lianyungang, 222000, China. [email protected].
  • 5 Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang, 222005, China. [email protected].
  • # Contributed equally.
PMID: 38717633 DOI: 10.1007/s10753-024-02041-2
Abstract

Currently, treatment options for acute lung injury (ALI) are limited. Gypenoside XLIX (Gyp-XLIX) is known for its anti-inflammatory properties, but there is a lack of extensive research on its effects against ALI. This study induced ALI in mice through cecal ligation and puncture surgery and investigated the biological activity and potential mechanisms of Gypenoside XLIX (40 mg/kg) by intraperitoneal injection. The in vitro ALI model was established using mouse lung epithelial (MLE-12) cells stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Various methods, including Hematoxylin and Eosin (H&E) staining, biochemical assay kits, Quantitative Polymerase Chain Reaction (qPCR) analysis, Western blotting, Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay, immunofluorescence, and flow cytometry, were employed for this research. The results indicated that pretreatment with Gypenoside XLIX significantly alleviated pathological damage in mouse lung tissues and reduced the expression levels of inflammatory factors. Additionally, Gypenoside XLIX inhibited ROS levels and NLRP3 inflammasome, possibly mediated by the SIRT1/Nrf2 signaling pathway. Moreover, Gypenoside XLIX significantly inhibited sepsis-induced lung cell Apoptosis and excessive Autophagy of mitochondria. Specifically, it suppressed mitochondrial pathway Apoptosis and the Pink1/Parkin pathway of mitochondrial Autophagy. These findings reveal the multifaceted effects of Gypenoside XLIX in anti-inflammatory, antioxidative, and inhibition of cell Apoptosis and Autophagy. This provides strong support for its therapeutic potential in sepsis-related lung injuries.

Keywords

ALI; NLRP3; Sirt1/Nrf2; cell apoptosis; gypenoside XLIX; mitochondrial autophagy.

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