PMID- 36367170
OWN - NLM
STAT- MEDLINE
DCOM- 20221114
LR  - 20221127
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 27
IP  - 1
DP  - 2023 Jan
TI  - Metabolomic analysis and pharmacological validation of the cerebral protective 
      effect of 3,4‑dihydroxybenzaldehyde on cerebral ischemia‑reperfusion injury.
LID - 9 [pii]
LID - 10.3892/mmr.2022.12896 [doi]
AB  - 3,4‑Dihydroxybenzaldehyde (DBD), one of the active components of Gastrodia elata, 
      has a cerebral protective effect and can effectively combat cerebral 
      ischemia/reperfusion (I/R) injury in rats. However, the metabolite profiles and 
      underlying mechanisms associated with DBD remain unclear. To explore the level of 
      energy metabolism and pharmacological targets in brain tissue following DBD 
      treatment of stroke. The right middle cerebral artery of the rats was occluded 
      for 2 h and reperfused for 24 h to simulate brain I/R injury. Pharmacological 
      results showed that DBD reduced cerebral infarct volume, improved neurological 
      function and increased adenosine triphosphate (ATP) content. Mitochondria are the 
      primary sites for ATP generation and cellular energy supply and decreasing 
      mitochondrial dysfunction can alleviate the energy expenditure of ischemic 
      stroke. Through further experiments, it was found that mitochondrial damage was 
      recovered following DBD treatment, which was manifested by the improvement of 
      mitochondrial morphology under an electron microscope and the reduction of 
      oxidative stress damage. The metabolomics of middle cerebral artery 
      occlusion/reperfusion (MCAO/R) rat brain tissue was studied by the liquid 
      chromatography‑tandem mass spectrometry metabolomics method. Significantly 
      different metabolites were screened and the pathways involved included amino 
      sugar and nucleotide sugar metabolism and pentose phosphate pathway. Finally, the 
      present study performed targeted metabolic profiling and validated potential 
      therapeutic targets. Uridine diphosphate N‑acetylglucosamine (UDP‑GlcNAc) levels 
      were decreased in the MCAO/R group but significantly increased in the DBD group. 
      TdT‑mediated dUTP nick end labeling (TUNEL) staining, hematoxylin and eosin 
      staining and western blotting showed that brain cell apoptosis was inhibited and 
      neuronal morphology improved. Among them, the regulatory enzyme O‑GlcNAc 
      transferase (OGT) of UDP‑GlcNAc appeared to be significantly increased and 
      neuronal apoptosis was inhibited following DBD treatment, which was verified by 
      western blotting. Therefore, by analyzing mitochondrial dysfunction following I/R 
      and the characterization of potential markers in mitochondrial energy metabolism, 
      it was shown that OGT could inhibit neuronal apoptosis as a potential therapeutic 
      target for brain I/R injury.
FAU - Luo, Yuan
AU  - Luo Y
AD  - Yunnan Key Laboratory of Dai and Yi Medicine, Yunnan University of Chinese 
      Medicine, Kunming, Yunnan 650500, P.R. China.
FAU - Chen, Pu
AU  - Chen P
AD  - Yunnan Key Laboratory of Dai and Yi Medicine, Yunnan University of Chinese 
      Medicine, Kunming, Yunnan 650500, P.R. China.
FAU - Yang, Liping
AU  - Yang L
AD  - Yunnan Key Laboratory of Dai and Yi Medicine, Yunnan University of Chinese 
      Medicine, Kunming, Yunnan 650500, P.R. China.
FAU - Duan, Xiaohua
AU  - Duan X
AD  - Yunnan Key Laboratory of Dai and Yi Medicine, Yunnan University of Chinese 
      Medicine, Kunming, Yunnan 650500, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20221111
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 4PVP2HCH4T (protocatechualdehyde)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 58-98-0 (Uridine Diphosphate)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Brain Ischemia/metabolism
MH  - *Reperfusion Injury/metabolism
MH  - Apoptosis
MH  - Infarction, Middle Cerebral Artery/drug therapy
MH  - Adenosine Triphosphate/pharmacology
MH  - Uridine Diphosphate
PMC - PMC9685269
OTO - NOTNLM
OT  - 3
OT  - 4‑dihydroxybenzaldehyde
OT  - O‑GlcNAc transferase
OT  - ischemic stroke
OT  - metabolomics
OT  - mitochondrial dysfunction
OT  - uridine diphosphate N‑acetylglucosamine
COIS- The authors declare that they have no competing interests.
EDAT- 2022/11/12 06:00
MHDA- 2022/11/15 06:00
PMCR- 2022/11/11
CRDT- 2022/11/11 06:03
PHST- 2022/08/12 00:00 [received]
PHST- 2022/10/28 00:00 [accepted]
PHST- 2022/11/11 06:03 [entrez]
PHST- 2022/11/12 06:00 [pubmed]
PHST- 2022/11/15 06:00 [medline]
PHST- 2022/11/11 00:00 [pmc-release]
AID - 9 [pii]
AID - MMR-27-01-12896 [pii]
AID - 10.3892/mmr.2022.12896 [doi]
PST - ppublish
SO  - Mol Med Rep. 2023 Jan;27(1):9. doi: 10.3892/mmr.2022.12896. Epub 2022 Nov 11.