Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea; Center for Neuroscience, Korea Institute of Science & Technology, Seoul 02792, Republic of Korea.
Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Neuropharmacology. 2017 Nov;126:168-178. doi: 10.1016/j.neuropharm.2017.09.014. Epub 2017 Sep 9.
Schizophrenia is a chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Primary treatments for schizophrenia relieve the positive symptoms but are less effective against the negative and cognitive symptoms. In the present study, we investigated whether maslinic acid, isolated from Syzygium aromaticum (clove), can ameliorate schizophrenia-like behaviors in mice induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. After maslinic acid treatment in the MK-801 model, we examined the behavioral alteration and signaling pathways in the prefrontal cortex. Mice were treated with maslinic acid (30 mg/kg), and their behaviors were evaluated through an array of behavioral tests. The effects of maslinic acid were also examined in the signaling pathways in the prefrontal cortex. A single administration of maslinic acid blocked the MK-801-induced hyperlocomotion and reversed the MK-801-induced sensorimotor gating deficit in the acoustic startle response test. In the social novelty preference test, maslinic acid ameliorated the social behavior deficits induced by MK-801. The MK-801-induced attention and recognition memory impairments were also alleviated by a single administration of maslinic acid. Furthermore, maslinic acid normalized the phosphorylation levels of Akt-GSK-3β and ERK-CREB in the prefrontal cortex. Overall, maslinic acid ameliorated the schizophrenia-like symptoms induced by MK-801, and these effects may be partly mediated through Akt-GSK-3β and ERK-CREB activation. These findings suggest that maslinic acid could be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, social interaction deficits, and cognitive impairments.
精神分裂症是一种以阳性、阴性和认知症状为特征的慢性精神病。精神分裂症的主要治疗方法可缓解阳性症状，但对阴性和认知症状的疗效较差。本研究旨在探讨从丁香（Syzygium aromaticum）中分离出的齐墩果酸是否可以改善 MK-801（一种 N-甲基-D-天冬氨酸（NMDA）受体拮抗剂）诱导的精神分裂症样行为。在齐墩果酸治疗 MK-801 模型后，我们检测了前额叶皮质中的行为改变和信号通路。通过一系列行为测试评估了小鼠接受齐墩果酸（30mg/kg）治疗后的行为变化。还研究了齐墩果酸对前额叶皮质信号通路的影响。单次给予齐墩果酸可阻断 MK-801 诱导的过度活跃，并逆转在声发射反应测试中诱导的感觉运动门控缺陷。在社会新颖性偏好测试中，齐墩果酸改善了由 MK-801 引起的社会行为缺陷。单次给予齐墩果酸还减轻了 MK-801 引起的注意力和识别记忆障碍。此外，齐墩果酸使前额叶皮质中 Akt-GSK-3β 和 ERK-CREB 的磷酸化水平正常化。总体而言，齐墩果酸改善了由 MK-801 诱导的精神分裂症样症状，这些作用可能部分通过 Akt-GSK-3β 和 ERK-CREB 的激活介导。这些发现表明，齐墩果酸可能是治疗几种精神分裂症症状的候选药物，包括阳性症状、感觉运动门控障碍、社会互动缺陷和认知障碍。
