l-Borneol ameliorates cerebral ischaemia by downregulating the mitochondrial calcium uniporter-induced apoptosis cascade in pMCAO rats.

Abstract

OBJECTIVES:

Stroke is one of the leading causes of disability and death worldwide, and ischaemic stroke is the most common subtype. Moreover, we found that L-borneol has an obvious therapeutic effect on cerebral ischaemia. This study aimed to investigate the potential mechanism of L-borneol in permanent middle cerebral artery occlusion (pMCAO) rats via the mitochondrial calcium uniporter (MCU)-related apoptosis cascade.

METHODS:

A pMCAO model was used to simulate cerebral ischaemia, and neurological function was evaluated. Cerebral infarction was observed by TTC staining. HE staining was also used to reflect the pathophysiological changes in the rat hippocampus and cortex. Furthermore, MCU-related signals and apoptosis signalling pathways were detected at both the gene and protein levels.

RESULTS:

The neurological function scores of the high-dose L-borneol (H-B) group, medium-dose L-borneol (M-B) group and low-dose L-borneol (L-B) group were significantly lower than that of the model group at 24 h (P < 0.05, P < 0.01). High and medium doses of L-borneol could reverse the cerebral infarction area, similar to Nimotop. After HE staining, the cells in the H-B group and M-B group were neatly and densely arranged, with largely normal morphological structures. High-dose L-borneol could significantly reduce the gene and protein levels of Apaf-1, Bad and Caspase-3 and increase the expression of Bcl-2 (P < 0.05, P < 0.01). In addition, the MCU expression of the H-B group was significantly decreased compared with that of the model group at both the gene and protein levels (P < 0.05, P < 0.01). The expression of IDH2 was similar to that of MCU but not MEP (P < 0.05, P < 0.01).

CONCLUSION:

L-borneol can achieve brain protection by downregulating the excessive expression of MCU-related signalling pathway and further inhibiting the apoptosis of neurons during pMCAO.

• Authors: Wenwen Zhang, Jianxia Wen, Yinxiao Jiang, Qichao Hu, Jian Wang, Shizhang Wei, Haotian Li, Xiao Ma
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 73 Issue 2 Pg. 272-280 (Mar 04 2021) ISSN: 2042-7158 [Electronic] England
• PMID: 33793797 (Publication Type: Comparative Study, Journal Article)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Calcium Channels
• Camphanes
• Neuroprotective Agents
• mitochondrial calcium uniporter
• Nimodipine
• Idh2 protein, rat
• Isocitrate Dehydrogenase
• isoborneol

Topics

• Animals
• Apoptosis (drug effects)
• Brain Ischemia (drug therapy, pathology)
• Calcium Channels (metabolism)
• Camphanes (administration & dosage, pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Infarction, Middle Cerebral Artery
• Isocitrate Dehydrogenase (genetics)
• Male
• Neuroprotective Agents (administration & dosage, pharmacology)
• Nimodipine (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)