Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, China.
Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, China; Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08554, USA.
J Nutr Biochem. 2018 May;55:219-228. doi: 10.1016/j.jnutbio.2018.01.016. Epub 2018 Feb 9.
Human natural killer-1 (HNK-1) cell antigen is a glycan epitope involved in several neural events, such as neuritogenesis, myelination, synaptic plasticity and regeneration of the nervous system after injury. We have recently identified the small organic compound ursolic acid (UA) as a HNK-1 mimetic with the aim to test its therapeutic potential in the central nervous system. UA, a plant-derived pentacyclic triterpenoid, is well known for its multiple biological functions, including neuroprotective, antioxidant and anti-inflammatory activities. In the present study, we evaluated its functions in a mouse model of spinal cord injury (SCI) and explored the molecular mechanisms underlying its positive effects. Oral administration of UA to mice 1 h after SCI and thereafter once daily for 6 weeks enhanced the regaining of motor functions and axonal regrowth, and decreased astrogliosis. UA administration decreased levels of proinflammatory markers, including interleukin-6 and tumor necrosis factor-α, in the injured spinal cord at the acute phase of inflammation and activated the mitogen-activated protein kinase and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways in the injured spinal cord. Taken together, these results suggest that UA may be a candidate for treatment of nervous system injuries.
人自然杀伤细胞-1 (HNK-1) 细胞抗原是一种糖基表位，参与多种神经事件，如神经突生成、髓鞘形成、突触可塑性和神经系统损伤后的再生。我们最近发现，小分子有机化合物熊果酸 (UA) 是一种 HNK-1 模拟物，旨在测试其在中枢神经系统中的治疗潜力。UA 是一种植物来源的五环三萜，以其多种生物学功能而闻名，包括神经保护、抗氧化和抗炎作用。在本研究中，我们评估了 UA 在脊髓损伤 (SCI) 小鼠模型中的作用，并探讨了其积极作用的分子机制。SCI 后 1 小时给予 UA 口服治疗，并在接下来的 6 周内每天一次，可增强运动功能的恢复和轴突再生，并减少星形胶质细胞增生。UA 给药可降低损伤脊髓中炎症急性期的促炎标志物（包括白细胞介素-6 和肿瘤坏死因子-α）的水平，并激活损伤脊髓中的丝裂原活化蛋白激酶和磷酸肌醇 3-激酶/蛋白激酶 B/雷帕霉素哺乳动物靶蛋白途径。综上所述，这些结果表明 UA 可能是治疗神经系统损伤的候选药物。
