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Echinatin alleviates inflammation and pyroptosis in hypoxic-ischemic brain damage by inhibiting TLR4/ NF-κB pathway.
Tao, Xiaoyue; Hu, Yingying; Mao, Niping; Shen, Ming; Fang, Mingchu; Zhang, Min; Lou, Jia; Fang, Yu; Guo, Xiaoling; Lin, Zhenlang.
Afiliación
  • Tao X; Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zheji
  • Hu Y; Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zheji
  • Mao N; Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zheji
  • Shen M; Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zheji
  • Fang M; Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zheji
  • Zhang M; Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zheji
  • Lou J; Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zheji
  • Fang Y; Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zheji
  • Guo X; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, Zhejiang, 325027, China; Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang,325027, China. Electronic address: guoxling@hot
  • Lin Z; Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang, 325027, China; Key Laboratory of Structural Malformations in Children of Zheji
Int Immunopharmacol ; 136: 112372, 2024 Jul 30.
Article en En | MEDLINE | ID: mdl-38850784
ABSTRACT
Hypoxic ischemic encephalopathy (HIE) is a primary cause of neonatal death and disabilities. The pathogenetic process of HIE is closely associated with neuroinflammation. Therefore, targeting and suppressing inflammatory pathways presents a promising therapeutic strategy for the treatment of HIE. Echinatin is an active component of glycyrrhiza, with anti-inflammatory and anti-oxidative properties. It is commonly combined with other traditional Chinese herbs to exert heat-clearing and detoxifying effects. This study aimed to investigate the anti-inflammatory and neuroprotective effects of Echinatin in neonatal rats with hypoxic-ischemic brain damage, as well as in PC12 cells exposed to oxygen-glucose deprivation (OGD). In vivo, Echinatin effectively reduced cerebral edema and infarct volume, protected brain tissue morphology, improved long-term behavioral functions, and inhibited microglia activation. These effects were accompanied by the downregulation of inflammatory factors and pyroptosis markers. The RNA sequencing analysis revealed an enrichment of inflammatory genes in rats with hypoxic-ischemic brain damage, and Protein-protein interaction (PPI) network analysis identified TLR4, MyD88, and NF-κB as the key regulators. In vitro, Echinatin reduced the levels of TLR4 relevant proteins, inhibited nuclear translocation of NF-κB, reduced the expression of downstreams inflammatory cytokines and pyroptosis proteins, and prevented cell membrane destructions. These findings demonstrated that Echinatin could inhibit the TLR4/NF-κB pathway, thereby alleviating neuroinflammation and pyroptosis. This suggests that Echinatin could be a potential candidate for the treatment of HIE.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / FN-kappa B / Ratas Sprague-Dawley / Fármacos Neuroprotectores / Hipoxia-Isquemia Encefálica / Receptor Toll-Like 4 / Piroptosis Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / FN-kappa B / Ratas Sprague-Dawley / Fármacos Neuroprotectores / Hipoxia-Isquemia Encefálica / Receptor Toll-Like 4 / Piroptosis Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos