Neuroprotective Mechanisms of Calycosin Against Focal Cerebral Ischemia and Reperfusion Injury in Rats.

Abstract

BACKGROUND/AIMS:

Emerging evidence suggests that autophagy plays important roles in the pathophysiological processes of cerebral ischemia and reperfusion injury. Calycosin, an isoflavone phytoestrogen, possesses neuroprotective effects in cerebral ischemia and reperfusion in rats. Here, we investigated the neuroprotective effects of calycosin against ischemia and reperfusion injury, as well as related probable mechanisms behind autophagy pathways.

METHODS:

A cerebral ischemic and reperfusion injury model was established by middle cerebral artery occlusion in male Sprague-Dawley rats. Neurological scores, infarct volumes, and brain water content were assessed after 24 h reperfusion following 2 h ischemia. Additionally, the expression of the autophagy-related protein p62 and NBR1 (neighbor of BRCA1 gene 1), as well as Bcl-2, and TNF-α in rat brain tissues was measured by RT-PCR, western blotting and immunohistochemical analyses.

RESULTS:

The results showed that calycosin pretreatment for 14 days markedly decreased infarct volume and brain edema, and ameliorated neurological scores in rats with focal cerebral ischemia and reperfusion. It was observed that levels of p62, NBR1 and Bcl-2 were greatly decreased, and levels of TNF-α significantly increased after ischemia and reperfusion injury. However, calycosin administration dramatically upregulated the expression of p62, NBR1 and Bcl-2, and downregulated the level of TNF-α.

CONCLUSIONS:

All data reveal that calycosin exerts a neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms maybe associated with its anti-autophagic, anti-apoptotic and anti-inflammatory action.

• Authors: Yong Wang, Qianyao Ren, Xing Zhang, Huiling Lu, Jian Chen
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 45 Issue 2 Pg. 537-546 ( 2018) ISSN: 1421-9778 [Electronic] Germany
• PMID: 29402799 (Publication Type: Journal Article)
• Copyright: © 2018 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Isoflavones
• Nbr1 protein, rat
• Neuroprotective Agents
• Proteins
• Proto-Oncogene Proteins c-bcl-2
• Sequestosome-1 Protein
• Sqstm1 protein, rat
• Tumor Necrosis Factor-alpha
• 7,3'-dihydroxy-4'-methoxyisoflavone

Topics

• Animals
• Brain (metabolism)
• Brain Ischemia (etiology, pathology, prevention & control)
• Disease Models, Animal
• Down-Regulation (drug effects)
• Infarction, Middle Cerebral Artery (complications)
• Isoflavones (chemistry, pharmacology, therapeutic use)
• Male
• Neuroprotective Agents (chemistry, pharmacology, therapeutic use)
• Proteins (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (etiology, pathology, prevention & control)
• Sequestosome-1 Protein (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation (drug effects)