Fructus mume alleviates chronic cerebral hypoperfusion-induced white matter and hippocampal damage via inhibition of inflammation and downregulation of TLR4 and p38 MAPK signaling

BMC Complementary and Alternative Medicine

Research Article

Bang Yeon Hwang¹  Jung-Soo Han²  Won Kyung Jeon³  Bu Yeo Kim³  In Sun Lee³  Ki Mo Lee³  JiHye Bang³ 

[1] College of Pharmacy, Chungbuk National University, 361-763, Cheongju, Republic of Korea;Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, 143-701, Seoul, Republic of Korea;KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, 305-811, Daejeon, Republic of Korea;

关键词: Fructus mume;    Permanent bilateral common carotid artery occlusion;    Inflammation;    White matter;    Hippocampus;   

DOI  :  10.1186/s12906-015-0652-1

 received in 2013-12-27, accepted in 2015-04-15,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Lee et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.