Abstract
BackgroundFructus mume (F. mume) has been used as a traditional medicine for many years in Asian countries. The present study was designed to determine the effect of a 70% ethanol extract of F. mume on white matter and hippocampal damage induced by chronic cerebral hypoperfusion.MethodsPermanent bilateral common carotid artery occlusion (BCCAo) was performed on male Wistar rats to induce chronic cerebral hypoperfusion. Daily oral administration of F. mume (200 mg/kg) was initiated 21 days after BCCAo and continued for 42 days. The experimental groups in this study were divided into three groups: a sham-operated group, a BCCAo group, and a BCCAo group that was administered with the F. mume extract. The activation of glial cells, including microglia and astrocytes, and the levels of myelin basic protein (MBP), inflammatory mediators, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and p38 mitogen-activated protein kinase (MAPK) phosphorylation were measured in brains from rats subjected to chronic BCCAo.ResultsOur results revealed that F. mume alleviates the reduction in MBP expression caused by chronic BCCAo in the white matter and the hippocampus and significantly attenuates microglial and astrocytic activation induced by chronic BCCAo in the optic tract of white matter. In addition, F. mume treatment reduced the increased expression of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6), as well as the activation of TLR4/MyD88 and p38 MAPK signaling, in the hippocampus of rats subjected to chronic BCCAo.ConclusionTaken together, our findings demonstrate that brain injury induced by chronic BCCAo is ameliorated by the anti-inflammatory effects of F. mume via inhibition of MBP degradation, microglial and astrocytic activation, increased inflammatory mediator expression, and activated intracellular signalings, including TLR4 and p38 MAPK, implying that F. mume is potentially an effective therapeutics for the treatment of vascular dementia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-015-0652-1) contains supplementary material, which is available to authorized users.
Highlights
Fructus mume (F. mume) has been used as a traditional medicine for many years in Asian countries
We investigated the effects of F. mume on chronic BCCAoinduced myelin basic protein (MBP) breakdown in the medial septum, corpus callosum, and fimbria of the white matter and the hippocampus
Post-hoc analyses revealed that compared to the sham-operated controls, the expression level of MBP in the bilateral common carotid artery occlusion (BCCAo) rats treated with vehicle was apparently decreased in the medial septum, corpus callosum, and fimbria of the white matter and the hippocampus (Figure 1A and B)
Summary
Fructus mume (F. mume) has been used as a traditional medicine for many years in Asian countries. BCCAo immediately decreases CBF after occlusion and maintains a persistent reduction in CBF for several months [7]. This reduction in CBF of rats subjected to BCCAo exhibits regional differences in various brain structures. CBF decreased by 35-45% of the normal level in the cortex and the white matter and declined by 60% of the normal level in the hippocampus of BCCAo-induced rats [5]. Experimental evidences have demonstrated that chronic cerebral hypoperfusion induced by BCCAo results in damage to white matter regions, especially the corpus callosum and the optic tract, because these regions are more vulnerable to persistent obstruction of the blood supply from the carotid artery [8,9,10]
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