Publication: Naoluotong granules inhibit necroptosis of neural cells and improve cerebral ischemia-reperfusion injury by regulating the RIP1/NIK/IKKα/NF-κB pathway
Authors
Wei Dong ; Liangyong Li ; Wenming Yang ; Yajun Li
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Publisher
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Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-25-035
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info:eu-repo/semantics/article
Description
Abstract
Background. Cerebral ischemia-reperfusion
can cause structural changes in brain tissue and disrupt
physiological functions. Naoluotong granules (NLT)
exhibit significant neuroprotective effects on brain nerve
cells and are widely utilized in treating cerebral
ischemia-reperfusion injury (CIRI). However, the
underlying molecular mechanisms remain elusive.
Methods. The CIRI model was established in vivo,
with rats assigned to four groups. 2,3,5-triphenyltetra
zolium chloride (TTC), hematoxylin and eosin (H&E),
and terminal deoxynucleotidyl transferase dUTP nick
end labeling (TUNEL) were used to evaluate the effects
of NLT and AST-IV on neurological function and
pathological injury after cerebral ischemia-reperfusion.
immunofluorescence, real-time PCR, and Western-blot
assays were performed to explore the effects of NLT and
AST-IV on the RIP1/NIK/IKKα/NF-κB pathway. The
micro-enzyme immunoassay method was applied to
examine the expression levels of various factors in each
group. To verify the neuroprotective effects of NLT and
AST-IV in vitro, an oxygen-glucose deprivation/re
oxygenation (OGD/R) PC12 cell model was established
and treated with the drug-containing serum of NLT and
AST-IV.
Results. Necroptosis plays a significant role in the
onset and progression of ischemia-reperfusion-induced
neural injury. In vivo studies have shown that both NLT
and AST-IV improve neurological function scores,
reduce infarct volume, and enhance pathological features
following MCAO/R.
They significantly inhibited the expression of the
RIP1/NIK/IKKα/NF-κB pathway, thereby reducing
neuronal cell necroptosis. In vitro studies also showed that NLT and AST-IV reduced OGD/R-induced
necroptosis.
Conclusions. This study confirms that the significant
neuroprotective effects of NLT and AST-IV in
alleviating CIRI are related to inhibiting necrosis by
suppressing the RIP1/NIK/IKKα/NF-κB pathway.
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