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

被引:0
|
作者
Ping, Kaixin [1 ,3 ]
Yang, Rongrong [2 ]
Chen, Huizhen [3 ]
Xie, Shaocheng [1 ]
Xiang, Yannan [1 ,2 ]
Li, Mengxin [1 ,3 ]
Lu, Yingzhi [2 ]
Dong, Jingquan [1 ]
机构
[1] Jiangsu Ocean Univ, Jiangsu Key Lab Marine Bioresources & Environm, Coinnovat Ctr Jiangsu Marine Bioind Technol, Jiangsu Marine Pharmaceut Resources Dev Engn Res C, Lianyungang 222005, Peoples R China
[2] Nanjing Med Univ, Dept Oncol, Peoples Hosp Lianyungang 2, Oncol Hosp Lianyungang,Kangda Coll, Lianyungang 222000, Peoples R China
[3] First Peoples Hosp Lianyungang, Inst Neurosci, Neurosurg Dept, Lianyungang 222005, Peoples R China
关键词
gypenoside XLIX; Sirt1/Nrf2; NLRP3; mitochondrial autophagy; cell apoptosis; ALI; KAPPA-B; APOPTOSIS; SEPSIS; EXPRESSION; AUTOPHAGY; PROTEIN; PPAR;
D O I
10.1007/s10753-024-02041-2
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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收藏
页码:42 / 60
页数:19
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