title: Withaferin A protects against spinal cord injury by inhibiting apoptosis and inflammation in mice.
abstract: BACKGROUND
  Withaferin A (WFA) exhibits diverse pharmaceutical applications on human diseases, including rheumatoid arthritis, cancers and microbial infection.
  
  
  OBJECTIVE
  We evaluated the neuroprotective role of WFA using a mouse model of spinal cord injury (SCI).
  
  
  METHODS
  BALB/c mice were administrated 10 mg/kg of WFA. Gene expression was measured by real-time PCR, western blot and immunohistochemistry. Cell morphology and apoptosis were determined by H&E staining and TUNEL assay. Motor function was evaluated by the BBB functional scale for continuous 7 weeks.
  
  
  RESULTS
  WFA significantly improved neurobehavioural function and alleviated histological alteration of spinal cord tissues in traumatized mice. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) significantly increased in WFA-treated mice. Meanwhile, the expression of Nogo-A and RhoA remarkably decreased in the presence of WFA. Furthermore, the apoptotic cell death was attenuated in mice treated with WFA (31.48 ± 2.50% vs. 50.08 ± 2.08%) accompanied by decreased bax and increased bcl-2. In addition, WFA decreased the expression of pro-inflammatory mediators such as IL-1β (11.20 ± 1.96 ng/mL vs. 17.59 ± 1.42 ng/mL) and TNF-α (57.38 ± 3.57 pg/mL vs. 95.06 ± 9.13 pg/mL). The anti-inflammatory cytokines including TGF-β1 (14.32 ± 1.04 pg/mL vs. 9.37 ± 1.17 pg/mL) and IL-10 (116.80 ± 6.91 pg/mL vs. 72.33 ± 9.35 pg/mL) were elevated after WFA administration.
  
  
  CONCLUSIONS
  This study demonstrated that WFA has a neuroprotective role by inhibition of apoptosis and inflammation after SCI in mice.
authors.affiliation: a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China.
authors.forename: Xianlei
authors.initials: X
authors.lastname: Yan
authors.affiliation: b Department of Neurosurgery , The First Affiliated Hospital of Guangxi Medical University , Nanning , China.
authors.forename: Guangxiang
authors.initials: G
authors.lastname: Huang
authors.affiliation: a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China.
authors.forename: Jiemin
authors.initials: J
authors.lastname: Zheng
authors.affiliation: a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China.
authors.forename: Hongmou
authors.initials: H
authors.lastname: Chen
authors.affiliation: a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China.
authors.forename: Qidan
authors.initials: Q
authors.lastname: Huang
authors.affiliation: a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China.
authors.forename: Jiakang
authors.initials: J
authors.lastname: Chen
authors.affiliation: a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China.
authors.forename: Heqing
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000070798:Nogo Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D054358:Withanolides / Q000494:pharmacology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: D000893:Anti-Inflammatory Agents; D051017:Apoptosis Regulatory Proteins; D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse; D054358:Withanolides; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C009684:withaferin A
keywords: Central nervous system; anti-inflammatory cytokine; natural product; pro-inflammatory cytokine