PMID- 28228044 OWN - NLM STAT- MEDLINE DCOM- 20170309 LR - 20201209 IS - 1744-5116 (Electronic) IS - 1388-0209 (Print) IS - 1388-0209 (Linking) VI - 55 IP - 1 DP - 2017 Dec TI - Withaferin A protects against spinal cord injury by inhibiting apoptosis and inflammation in mice. PG - 1171-1176 LID - 10.1080/13880209.2017.1288262 [doi] AB - CONTEXT: 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). MATERIALS AND 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-1beta (11.20 +/- 1.96 ng/mL vs. 17.59 +/- 1.42 ng/mL) and TNF-alpha (57.38 +/- 3.57 pg/mL vs. 95.06 +/- 9.13 pg/mL). The anti-inflammatory cytokines including TGF-beta1 (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. DISCUSSION AND CONCLUSION: This study demonstrated that WFA has a neuroprotective role by inhibition of apoptosis and inflammation after SCI in mice. FAU - Yan, Xianlei AU - Yan X AD - a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China. FAU - Huang, Guangxiang AU - Huang G AD - b Department of Neurosurgery , The First Affiliated Hospital of Guangxi Medical University , Nanning , China. FAU - Liu, Quan AU - Liu Q AD - a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China. FAU - Zheng, Jiemin AU - Zheng J AD - a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China. FAU - Chen, Hongmou AU - Chen H AD - a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China. FAU - Huang, Qidan AU - Huang Q AD - a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China. FAU - Chen, Jiakang AU - Chen J AD - a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China. FAU - Huang, Heqing AU - Huang H AD - a Department of Neurosurgery , the Fourth Affiliated Hospital of Guangxi Medical University , Liuzhou , China. LA - eng PT - Journal Article PL - England TA - Pharm Biol JT - Pharmaceutical biology JID - 9812552 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Inflammation Mediators) RN - 0 (Neuroprotective Agents) RN - 0 (Nogo Proteins) RN - 0 (Rtn4 protein, mouse) RN - 0 (Withanolides) RN - EC 3.6.5.2 (RhoA protein, mouse) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) RN - L6DO3QW4K5 (withaferin A) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Apoptosis/*drug effects MH - Apoptosis Regulatory Proteins/metabolism MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/metabolism MH - Disease Models, Animal MH - Glial Cell Line-Derived Neurotrophic Factor/metabolism MH - Inflammation/metabolism/pathology/physiopathology/*prevention & control MH - Inflammation Mediators/metabolism MH - Mice, Inbred BALB C MH - Motor Activity/drug effects MH - Neuroprotective Agents/*pharmacology MH - Nogo Proteins/metabolism MH - Signal Transduction/drug effects MH - Spinal Cord/*drug effects/metabolism/pathology/physiopathology MH - Spinal Cord Injuries/*drug therapy/metabolism/pathology/physiopathology MH - Time Factors MH - Withanolides/*pharmacology MH - rho GTP-Binding Proteins/metabolism MH - rhoA GTP-Binding Protein PMC - PMC6130570 OTO - NOTNLM OT - Central nervous system OT - anti-inflammatory cytokine OT - natural product OT - pro-inflammatory cytokine EDAT- 2017/02/24 06:00 MHDA- 2017/03/10 06:00 PMCR- 2017/02/23 CRDT- 2017/02/24 06:00 PHST- 2017/02/24 06:00 [entrez] PHST- 2017/02/24 06:00 [pubmed] PHST- 2017/03/10 06:00 [medline] PHST- 2017/02/23 00:00 [pmc-release] AID - 1288262 [pii] AID - 10.1080/13880209.2017.1288262 [doi] PST - ppublish SO - Pharm Biol. 2017 Dec;55(1):1171-1176. doi: 10.1080/13880209.2017.1288262.