title: Honokiol downregulates Kruppel-like factor 4 expression, attenuates inflammation, and reduces histopathology after spinal cord injury in rats.
abstract: METHODS
  Randomized experimental study.
  
  
  OBJECTIVE
  To investigate the neuroprotective effect of honokiol (HNK) on rats subjected to traumatic spinal cord injury (SCI) and the molecular mechanisms.
  
  
  BACKGROUND
  Inflammation contributes to the secondary injury to the spinal cord. Honokiol has been used as a neuroprotective agent because of its strong antioxidant and anti-inflammatory properties. Kruppel-like factor 4 (Klf4) is a newly identified critical target for the anti-inflammatory effect of HNK. Whether HNK can inhibit inflammatory response in rat model of SCI through mediating the expression of Klf4 has yet to be elucidated.
  
  
  METHODS
  Eighty-four adult female Sprague-Dawley rats were randomly divided into 4 groups as sham, SCI, SCI + Vehicle (0.1% propylene glycol in saline, intraperitoneally), and SCI + HNK (20 mg/kg, intraperitoneally) groups. The influences of HNK on the proinflammatory cytokines, microglial activation, neutrophil infiltration, histological changes, and improvement in motor function were assessed.
  
  
  RESULTS
  In the SCI group, proinflammatory cytokines, microglial activation, neutrophil infiltration, and Klf4 expression levels were increased compared with the sham group (P < 0.001). HNK intervention downregulated the expression of Klf4, reduced the production of proinflammatory cytokines, inhibited microglial activation, and neutrophil infiltration (P < 0.05). Furthermore, HNK also reduced histopathology and improved functional outcome after traumatic SCI.
  
  
  CONCLUSIONS
  HNK reduces secondary tissue damage and improves locomotor function recovery after SCI through suppressing inflammatory response, and can be used as a potential therapeutic agent for SCI.
  
  
  METHODS
  NA.
authors.affiliation: *Departmentof Institute of Orthopaedics, Chinese PLA (People's Liberation Army) Beijing Army General Hospital, Beijing, China; and †Department of Medical School of Chinese PLA, Beijing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Changmeng
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.forename: Jianzheng
authors.initials: J
authors.lastname: Zhang
authors.forename: Zimin
authors.initials: Z
authors.lastname: Xiang
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Sun
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000032:analysis / Q000378:metabolism*; D017705:Lignans / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D016207:Cytokines; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D017705:Lignans; D018696:Neuroprotective Agents; C000715469:Klf4 protein, rat; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols