L-Borneol ameliorates cerebral ischaemia by downregulating the mitochondrial calcium uniporter-induced apoptosis cascade in pMCAO rats. (10th December 2020)

• Record Type: Journal Article
• Authors: Zhang, Wenwen; Wen, Jianxia; Jiang, Yinxiao; Hu, Qichao; Wang, Jian; Wei, Shizhang; Li, Haotian; Ma, Xiao
• Is Part Of: Journal of pharmacy and pharmacology. Volume 73:Number 2(2021)
• Page Start: 272
• Page End: 280
• Publication Date: 2020-12-10
• Subjects: L-Borneol -- cerebral ischaemia -- apoptosis -- mitochondrial calcium uniporter -- traditional chinese medicine; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1093/jpp/rgaa028
• Languages: English
• ISSNs: 0022-3573

Abstract

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.