title: Ginkgolide B reduces neuronal cell apoptosis in the hemorrhagic rat brain: possible involvement of Toll-like receptor 4/nuclear factor-kappa B pathway.
abstract: BACKGROUND
  Ginkgolide B (GB) is one of the ginkgolides that have been isolated from leaves and root bark of the Chinese tree Ginkgo biloba L. (Ginkgoaceae), and is a specific and potent antagonist of platelet activating factor. There is a large body of data showing that GB possesses a markedly neuroprotective property against ischemia-induced impairment in vivo and in vitro. Recently it has been found that GB can inhibit the inflammation in the rat brain tissues with ischemia/reperfusion injury and in the astrocytes treated with lipopolysaccharide, as well as protect neurons against beta-amyloid 25-35 and ischemia-induced apoptosis. However, there have been few reports on the influence of GB on intracerebral hemorrhage (ICH). This study was to investigate the effects of intraperitoneal GB on neuronal cell apoptosis, inflammatory cytokines and Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway after ICH.
  
  
  METHODS
  Wistar rats obtained an intraperitoneal injection of 5, 10 and 20mg/kg GB after ICH once a day till day 5. Rats were sacrificed by decapitation at hour 2, 6 and 12, as well as day 1, 2, 3 and 5 after ICH. Gene expressions of TLR-4 and NF-κB, concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) as well as number of apoptotic neuronal cells in hemorrhagic rat brain tissues were determined.
  
  
  RESULTS
  The administration of 10 and 20mg/kg GB could significantly suppress gene expressions of TLR-4 and NF-κB, lessen concentrations of TNF-α, IL-1β and IL-6 as well as reduce number of apoptotic neuronal cells in hemorrhagic rat brain tissues by Least-significant Difference test (P<0.05), but the administration of 5mg/kg GB not (P>0.05). However, a clear concentration-response relationship was not found.
  
  
  CONCLUSIONS
  GB may inhibit TLR4/NF-κB-dependent inflammatory responses, and furthermore lessen neuronal cell apoptosis after ICH, which may support the use of G. biloba extracts for the treatment of ICH.
authors: Department of Intensive Care Unit, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 Qingchun East Road, Hangzhou 310000, China.
authors: Yue-Yu
authors: YY
authors: Hu
authors: Man
authors: M
authors: Huang
authors: Xiao-Qiao
authors: XQ
authors: Dong
authors: Qiu-Ping
authors: QP
authors: Xu
authors: Wen-Hua
authors: WH
authors: Yu
authors: Zu-Yong
authors: ZY
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020441:Ginkgo biloba; D046934:Ginkgolides / Q000008:administration & dosage / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D046934:Ginkgolides; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D007783:Lactones; D016328:NF-kappa B; D018696:Neuroprotective Agents; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C045856:ginkgolide B