Lab Anim Res.  2022 Dec;38(4):345-355. 10.1186/s42826-022-00151-2.

Chlorogenic acid modulates the ubiquitin– proteasome system in stroke animal model

• Shah M
• Kang J
• Koh P

• KMID: 2537638
• DOI: http://doi.org/10.1186/s42826-022-00151-2

Abstract

Background
Chlorogenic acid, a phenolic compound, has potent antioxidant and neuroprotective properties. The ubiquitin–proteasome system is an important regulators of neurodevelopment and modulators of neuronal function. This system is associated with neurodevelopment and neurotransmission through degradation and removal of dam‑ aged proteins. Activation of the ubiquitin–proteasome system is a critical factor in preventing cell death. We have pre‑ viously reported a decrease in the activity of the ubiquitin–proteasome system during cerebral ischemia. This study investigated whether chlorogenic acid regulates the ubiquitin–proteasome system in an animal stroke model. In adult rats, middle cerebral artery occlusion (MCAO) surgery was performed to induce focal cerebral ischemia. Chlorogenic acid (30 mg/kg) or normal saline was injected into the abdominal cavity 2 h after MCAO surgery, and cerebral cortex tissues were collected 24 h after MCAO damage.
Results
Chlorogenic acid attenuated neurobehavioral disorders and histopathological changes caused by MCAO damage. We identified the decreases in ubiquitin C-terminal hydrolase L1, ubiquitin thioesterase OTUB1, proteasome subunit α type 1, proteasome subunit α type 3, and proteasome subunit β type 4 expression using a proteomics approach in MCAO animals. The decrease in these proteins was alleviated by chlorogenic acid. In addition, the results of reverse transcription-polymerase chain reaction confirmed these changes. The identified proteins were markedly reduced in MCAO damage, while chlorogenic acid prevented these reductions induced by MCAO. The decrease of ubiquitin–proteasome system proteins in ischemic damage was associated with neuronal apoptosis.
Conclusions
Our results showed that chlorogenic acid regulates ubiquitin–proteasome system proteins and pro‑ tects cortical neurons from neuronal damage. These results provide evidence that chlorogenic acid has neuroprotec‑ tive effects and maintains the ubiquitin–proteasome system in ischemic brain injury.

Keyword

Cerebral ischemia; Chlorogenic acid; Neuroprotection; Ubiquitin–proteasome system