title: Fructus mume alleviates chronic cerebral hypoperfusion-induced white matter and hippocampal damage via inhibition of inflammation and downregulation of TLR4 and p38 MAPK signaling.
abstract: BACKGROUND
  Fructus 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.
  
  
  METHODS
  Permanent 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.
  
  
  RESULTS
  Our 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.
  
  
  CONCLUSIONS
  Taken 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.
authors.affiliation: KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea. lkm4703@kiom.re.kr.
authors.forename: Ki Mo
authors.initials: KM
authors.lastname: Lee
authors.affiliation: KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea. fart0920@kiom.re.kr.
authors.forename: JiHye
authors.initials: J
authors.lastname: Bang
authors.affiliation: KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea. buykim@kiom.re.kr.
authors.forename: Bu Yeo
authors.initials: BY
authors.lastname: Kim
authors.affiliation: KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea. yiinsun2@naver.com.
authors.forename: In Sun
authors.initials: IS
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701, Republic of Korea. jshan06@konkuk.ac.kr.
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, 361-763, Republic of Korea. byhwang@chungbuk.ac.kr.
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.affiliation: KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea. wkjeon@kiom.re.kr.
authors.forename: Won Kyung
authors.initials: WK
authors.lastname: Jeon
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015140:Dementia, Vascular / Q000378:metabolism* / Q000517:prevention & control; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D027861:Prunus; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D066127:White Matter / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D004676:Myelin Basic Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D048051:p38 Mitogen-Activated Protein Kinases