Withaferin A protects against spinal cord injury by inhibiting apoptosis and inflammation in mice

• Published in: Pharmaceutical biology 2017-01, Vol.55 (1), p.1171-1176
• Main Authors: Yan, Xianlei, Huang, Guangxiang, Liu, Quan, Zheng, Jiemin, Chen, Hongmou, Huang, Qidan, Chen, Jiakang, Huang, Heqing
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; anti-inflammatory cytokine; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Bcl-2 protein; Behavior, Animal - drug effects; Blood-brain barrier; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cell death; Central nervous system; Cytology; Disease Models, Animal; Gene expression; Glial cell line-derived neurotrophic factor; Glial Cell Line-Derived Neurotrophic Factor - metabolism; IL-1β; Immunohistochemistry; Inflammation; Inflammation - metabolism; Inflammation - pathology; Inflammation - physiopathology; Inflammation - prevention & control; Inflammation Mediators - metabolism; Interleukin 10; Mice, Inbred BALB C; Motor Activity - drug effects; natural product; Neuronal-glial interactions; Neuroprotection; Neuroprotective Agents - pharmacology; Nogo protein; Nogo Proteins - metabolism; pro-inflammatory cytokine; Rheumatoid arthritis; rho GTP-Binding Proteins - metabolism; RhoA protein; Rodents; Signal Transduction - drug effects; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal Cord - physiopathology; Spinal cord injuries; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; Time Factors; Transforming growth factor-b1; Traumatic brain injury; Tumor necrosis factor-α; Withanolides - pharmacology
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2017.1288262

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-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. Discussion and conclusion: This study demonstrated that WFA has a neuroprotective role by inhibition of apoptosis and inflammation after SCI in mice.