Plasma metabonomic study on the effect of Parahydroxybenzaldehyde intervention in a rat model of transient focal cerebral ischemia.
Mol Med Rep
; 28(5)2023 Nov.
Article
in En
| MEDLINE
| ID: mdl-37800608
ABSTRACT
Gastrodia elata Blume has been widely used to treat various central and peripheral nerve diseases, and Parahydroxybenzaldehyde (PHBA) is one of the indicated components suggested to provide a neuroprotective effect. In our previous, it was shown that PHBA protected mitochondria against cerebral ischemiareperfusion (I/R) injury in rats. In the present study, how PHBA regulated the metabolic mechanism in blood following cerebral I/R was assessed to identify an effective therapeutic target for the prevention and treatment of ischemic stroke (IS). First, a rat model of cerebral ischemiareperfusion injury was established via middle cerebral artery occlusion/reperfusion (MCAO/R). The therapeutic effect of PHBA on brain I/R was evaluated by assessing the neurological function score, triphenyl tetrazolium chloride, hematoxylin and eosin, and Nissl staining. Next, a nontargeted metabolomic based on highperformance liquid chromatography quadrupole timeofflight mass spectrometry was established to identify differential metabolites. Finally, a targeted metabolic spectrum was analyzed and the potential therapeutic targets were verified by Western blotting. The results showed that the neurological function score, cerebral infarction area, hippocampal morphology, and the number of neurons in the PHBA group were significantly improved compared with the model group. Metabonomic analysis showed that 13 different metabolites were identified between the model and PHBA group, which may be involved in the 'tricarboxylic acid cycle', 'glutathione metabolism', and 'mutual transformation of pentose and glucuronates', amongst others. Among these, the levels of the most significant differential metabolite, dGMP, decreased significantly following PHBA treatment. Western blotting was used to verify the expression of membraneassociated guanosine kinase PSD95 and the subunit of glutamate AMPA receptor GluA1, which significantly increased after PHBA treatment. In addition, it was also found that PHBA increased the expression of the light chain3 protein and autophagy effector protein 1, whilst the expression of sequestosome1 decreased, indicating that PHBA promoted autophagy. Similarly, in TUNEL staining and detection of apoptosisrelated proteins, it was found that MCAO/R upregulated the expression of Bax and cleavedcaspase3 whilst downregulating the expression of Bcl2 and increasing the apoptosis of hippocampal neurons; PHBA reversed this situation. These results suggest that cerebral I/R causes postsynaptic dysfunction by disrupting the interaction between PSD95 and AMPARs, and the inhibition of the autophagy system eventually leads to the apoptosis of hippocampal neurons.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Reperfusion Injury
/
Brain Ischemia
/
Ischemic Attack, Transient
/
Neuroprotective Agents
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mol Med Rep
Year:
2023
Document type:
Article