Jia Liu1, Changmeng Zhang, Zhi Liu, Jianzheng Zhang, Zimin Xiang, Tiansheng Sun. 1. *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.
Abstract
STUDY DESIGN: 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. SUMMARY OF BACKGROUND DATA: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: NA.
STUDY DESIGN: 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. SUMMARY OF BACKGROUND DATA: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: NA.
Authors: Harlan Barker; Marleena Aaltonen; Peiwen Pan; Maria Vähätupa; Pirkka Kaipiainen; Ulrike May; Stuart Prince; Hannele Uusitalo-Järvinen; Abdul Waheed; Silvia Pastoreková; William S Sly; Seppo Parkkila; Tero Ah Järvinen Journal: Exp Mol Med Date: 2017-05-19 Impact factor: 8.718