Antagonizing astrocytic platelet activating factor receptor-neuroinflammation for total flavone of epimedium in response to cuprizone demyelination.

Abstract

Demyelinating diseases of the central nervous system are characterized by recurrent demyelination and progressive neurodegeneration, but there are no clinical drugs targeting myelin regeneration or improving functional disability in the treatment of multiple sclerosis. Total flavone of Epimedium (TFE) is the main active components of Epimedium, which exhibits the beneficial biological activities in the treatment of diseases, but there is no report in the treatment of demyelinating disorder. The purpose of this study was to explore the therapeutic potential and possible mechanism of TFE in the treatment of demyelination. The results showed that TFE efficiently improved the behavioural performance and histological demyelination in cuprizone (CPZ)-induced demyelinating model. In terms of action, TFE increased astrocytes enrichment in corpus callosum, striatum and cortex, and promoted astrocytes to express neurotrophic factors. Furthermore, the expression of platelet-activating factor receptor (PAFR) in astrocytes was induced by CPZ feeding and LPS stimulation, accompanied by the increase of inflammatory cytokines TNF-α,IL-6 and IL-1β. TFE declined the expression of PAFR, and inhibited inflammatory response. At the same time, TFE also antagonized PAFR activation and inflammatory response triggered by PAF, which further confirmed that TFE, as a new PAFR antagonist, inhibited the astrocyte-derived inflammatory response by antagonizing PAFR-neuroinflammation axis, thus contributing to myelin protection and regeneration.

• Authors: Zhao Meng-Ru, Sui Ruo-Xuan, Yu Ming-Yang, Tian Tong, Zhang Lei, Yang Ying-Bo, Xiao Bao-Guo
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 101 Issue Pt A Pg. 108181 (Dec 2021) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 34607229 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Flavones
• Plant Extracts
• Platelet Membrane Glycoproteins
• Receptors, G-Protein-Coupled
• platelet activating factor receptor
• Cuprizone

Topics

• Administration, Oral
• Animals
• Astrocytes (drug effects, immunology, metabolism)
• Cuprizone (administration & dosage, toxicity)
• Demyelinating Diseases (chemically induced, drug therapy, immunology, pathology)
• Disease Models, Animal
• Epimedium (chemistry)
• Flavones (pharmacology, therapeutic use)
• Humans
• Male
• Mice
• Myelin Sheath (drug effects, immunology, pathology)
• Neuroinflammatory Diseases (chemically induced, drug therapy, immunology, pathology)
• Plant Extracts (pharmacology, therapeutic use)
• Platelet Membrane Glycoproteins (antagonists & inhibitors)
• Receptors, G-Protein-Coupled (antagonists & inhibitors)