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-1ß. 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.
Subject(s)
Demyelinating Diseases/drug therapy , Epimedium/chemistry , Neuroinflammatory Diseases/drug therapy , Plant Extracts/pharmacology , Platelet Membrane Glycoproteins/antagonists & inhibitors , Receptors, G-Protein-Coupled/antagonists & inhibitors , Administration, Oral , Animals , Astrocytes/drug effects , Astrocytes/immunology , Astrocytes/metabolism , Cuprizone/administration & dosage , Cuprizone/toxicity , Demyelinating Diseases/chemically induced , Demyelinating Diseases/immunology , Demyelinating Diseases/pathology , Disease Models, Animal , Flavones/pharmacology , Flavones/therapeutic use , Humans , Male , Mice , Myelin Sheath/drug effects , Myelin Sheath/immunology , Myelin Sheath/pathology , Neuroinflammatory Diseases/chemically induced , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/pathology , Plant Extracts/therapeutic useABSTRACT
It is uncommon for tire explosion related injuries on the lower extremity. The bilateral lower extremities were injured by tire explosion when the patient was seated in a bus. She sustained an open fracture with partial bone loss in the right calcaneus (a comminuted fracture in the right ankle joint) and a closed comminuted fracture in the left tibia and fibula. This damage was caused by uncontacted tire explosion, thanks to a thick floor between the exploded tire and the patient's feet. This type of injury on lower extremity caused by uncontacted tire explosion was uncommon.
