Traumatic brain injury (TBI) is a major cause of death and disability around the world with no effective treatments currently. The present study was aimed to investigate the neuroprotective effect of licoricidin, one of the major components of licorice extract, on TBI mice and further explore the underlying mechanism. Male C57BL/6 mice were modeled by a modified weight-drop method to mimic TBI. All animals received treatment 30 min after TBI. The modified Neurological Severity Score (NSS) tests were performed at 2 h and 1–3 days after TBI. The brain edema was analyzed by dry–wet weight method. The malonaldehyde (MDA) levels and the activities of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT) were determined by Elisa. Apoptotic neurons were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunofluorescence and the expression of apoptotic proteins were measured by western blot. Activation of the FoxO3/Wnt/β-catenin was evaluated by western blot. The results showed that treatment with licoricidin could significantly decline the NSS scores and reduce the brain edema, hence promote the recovery of neurological function in TBI mice. It also elevated the phosphorylation of p66^shc, brought down the levels of MDA, as well as antagonized the decrement in activities of GSH-PX, SOD and CAT induced by TBI. Moreover, licoricidin decreased the TUNEL positive neurons, downregulated the expression of Cyt-C, cleaved-Caspase-3, cleaved-Caspase-9 and Bax and upregulated the Bcl-2, attenuated cellular apoptosis. Licoricidin decreased the expression of FoxO3 and increased the Wnt/β-catenin in TBI mice. In conclusion, Licoricidin exerted neuroprotective effect on TBI model and the effect was possibly due to its antioxidative effect and antiapoptotic effect via regulating the FoxO3/Wnt/β-catenin pathway. Licoricidin may be a candidate drug for TBI therapy.

中文翻译：

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Licoricidin通过调节FoxO3 / Wnt /β-catenin途径改善小鼠颅脑损伤后的神经功能障碍。

创伤性脑损伤（TBI）是全球范围内导致死亡和残疾的主要原因，目前尚无有效的治疗方法。本研究旨在探讨甘草提取物的主要成分之一甘草苦素对TBI小鼠的神经保护作用，并进一步探讨其潜在机制。雄性C57BL / 6小鼠通过改良的减肥方法模拟TBI。TBI后30分钟，所有动物均接受治疗。改良的神经系统严重程度评分（NSS）测试在TBI后2小时和1-3天进行。用干湿重法分析脑水肿。Elisa测定了丙二醛（MDA）的水平以及谷胱甘肽过氧化物酶（GSH-PX），超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性。使用末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）免疫荧光检测凋亡神经元，并通过Western印迹检测凋亡蛋白的表达。通过蛋白质印迹评估FoxO3 / Wnt /β-catenin的激活。结果表明，用licoricidin处理可显着降低NSS评分并减轻脑水肿，从而促进TBI小鼠神经功能的恢复。它还提高了p66的磷酸化^shc降低了MDA的水平，并且对抗了TBI诱导的GSH-PX，SOD和CAT活性的降低。此外，licoricidin减少TUNEL阳性神经元，下调Cyt-C，Caspase-3裂解，Caspase-9裂解和Bax的表达，并上调Bcl-2，减弱细胞凋亡。Licoricidin降低TBI小鼠中FoxO3的表达并增加Wnt /β-catenin。总之，Licoricidin对TBI模型具有神经保护作用，其作用可能是由于其通过调节FoxO3 / Wnt /β-catenin途径的抗氧化作用和抗凋亡作用。Licoricidin可能是TBI治疗的候选药物。