title: Salvianolic Acids for Injection (SAFI) suppresses inflammatory responses in activated microglia to attenuate brain damage in focal cerebral ischemia.
abstract: BACKGROUND
  Inflammatory reactions induced by microglia in the brain play crucial roles in ischemia/reperfusion (I/R) cerebral injuries. Microglia activation has been shown to be closely related to TLR4/NF-κB signal pathways. Salvianolic acids for injection (SAFI) have been used in clinical practice to treat ischemic stroke with reported neuroprotective effects; however, the underlying mechanisms are still uncertain.
  
  
  OBJECTIVE
  First, we studied the effect of SAFI on inflammatory responses in LPS-stimulated BV-2 microglia. Then, to discover whether the beneficial in vitro effects of SAFI lead to in vivo therapeutic effects, an MCAO (Middle cerebral artery occlusion) rat model was further employed to elucidate the probable mechanism of SAFI in treating ischemic stroke. Rats in the SAFI group were given SAFI (23 or 46mg/kg) before I/R injury.
  
  
  RESULTS
  The results showed that SAFI treatment significantly decreased neuroinflammation and the infarction volume compared with the vehicle group. Activation of microglia cells was reduced, and TLR4/NF-κB signals, which were markedly inhibited by SAFI treatment in ischemic hemisphere, were accompanied by reduced expression and release of cytokines IL-1β and IL-6.
  
  
  CONCLUSIONS
  This study provides evidence that SAFI effectively protects the brain after cerebral ischemia, which may be caused by attenuating inflammation in microglia.
authors.affiliation: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin JF-Pharmaland Technology Development Co., Ltd., Tianjin, China.
authors.forename: Pengwei
authors.initials: P
authors.lastname: Zhuang
authors.affiliation: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Shihan
authors.initials: S
authors.lastname: Geng
authors.affiliation: Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin Key Laboratory of Safety Evaluation Enterprise of TCM Injections, Tianjin 300410, China; Tianjin Tasliy Pride Pharmaceutical Co., Ltd., Tianjin 300400, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.affiliation: Tianjin Key Laboratory of Safety Evaluation Enterprise of TCM Injections, Tianjin 300410, China; Tianjin Tasliy Pride Pharmaceutical Co., Ltd., Tianjin 300400, China.
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Tianjin Key Laboratory of Safety Evaluation Enterprise of TCM Injections, Tianjin 300410, China; Tianjin Tasliy Pride Pharmaceutical Co., Ltd., Tianjin 300400, China.
authors.forename: Dazheng
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Tianjin Key Laboratory of Safety Evaluation Enterprise of TCM Injections, Tianjin 300410, China; Tianjin Tasliy Pride Pharmaceutical Co., Ltd., Tianjin 300400, China.
authors.forename: Dekun
authors.initials: D
authors.lastname: Li
authors.affiliation: Tianjin JF-Pharmaland Technology Development Co., Ltd., Tianjin, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wei
authors.affiliation: Tianjin JF-Pharmaland Technology Development Co., Ltd., Tianjin, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. Electronic address: zyjsunye@163.com.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Safety Evaluation Enterprise of TCM Injections, Tianjin 300410, China; Tianjin Tasliy Pride Pharmaceutical Co., Ltd., Tianjin 300400, China. Electronic address: juach@tasly.com.
authors.forename: Aichun
authors.initials: A
authors.lastname: Ju
mesh_terms: D000475:Alkenes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D059808:Polyphenols / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000475:Alkenes; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D018696:Neuroprotective Agents; D059808:Polyphenols; D051197:Toll-Like Receptor 4; C568740:salvianolic acid
keywords: Inflammatory reaction; Ischemia/Reperfusion cerebral injury; Microglia; Salvianolic Acids for Injection; TLR4/NF-κB signals