Salvianolate lyophilized injection (SLI) strengthens blood-brain barrier function related to ERK1/2 and Akt signaling pathways.

Abstract

The salvianolate lyophilized injection (SLI) has been widely used for the treatment of acute cerebral infarction; however, the molecular mechanism of how it strengthens blood brain barrier (BBB) function is not well understood. Here, we investigated the effects of SLI on BBB function in bEnd.3 cells as well as in rats. In oxygen glucose deprivation/reoxygenation (OGD/R)-damaged bEnd.3 cells, SLI increased transepithelial electrical resistance and decreased sodium fluorescein flux. SLI-treated cells showed increased expression of tight junction proteins, including Zonula occludens-1 (ZO-1), Claudin-5 and Occludin. Furthermore, SLI led to the decrease of phosphorylation of ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of SLI on barrier function were abolished in cells in which ERK1/2 and Ak signaling were inhibited. Moreover, in MCAO model rats, SLI effectively alleviated brain leakage of Evans blue, increased brain tissue ZO-1 expression and inhibited phosphorylation of ERK1/2 and Akt. Overall, these data suggest that SLI strengthens BBB function was interrelated ERK1/2 and Akt signaling pathways in cerebral vascular diseases.

• Authors: Chun Zhao, Xueli Li, Xiaojin Li, Yangyang Xu, Mengmeng Ma, Shaoxia Wang, Lijuan Chai, Hong Guo, Limin Hu
• Journal: Brain research (Brain Res) Vol. 1720 Pg. 146295 (10 01 2019) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 31207213 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier B.V.

Chemical References

• Claudin-5
• Neuroprotective Agents
• Occludin
• Plant Extracts
• Tight Junction Proteins
• Zonula Occludens-1 Protein
• salvianolate
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Blood-Brain Barrier (drug effects, metabolism)
• Brain (metabolism)
• Brain Ischemia (metabolism)
• Cell Line
• Claudin-5 (metabolism)
• MAP Kinase Signaling System (drug effects, physiology)
• Male
• Mice
• Neuroprotective Agents (pharmacology)
• Occludin (metabolism)
• Plant Extracts (metabolism, pharmacology)
• Proto-Oncogene Proteins c-akt (drug effects, metabolism)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)
• Tight Junction Proteins (metabolism)
• Tight Junctions (drug effects)
• Zonula Occludens-1 Protein (metabolism)