Shin Jihwan, Lee Jeonghun, Choi Junhyuk, Ahn Byung-Taek, Jang Sang Chul, You Seung-Won, Koh Do-Yeon, Maeng Sungho, Cha Seung-Yun
Graduate School of East-West Medical Science, Kyung Hee University, Yong-in 17104, Republic of Korea.
AgeTech-Service Convergence Major, Graduated School of East-West Medical Science, Kyung Hee University, Young-in 17104, Republic of Korea.
Evid Based Complement Alternat Med. 2022 May 29;2022:6897359. doi: 10.1155/2022/6897359. eCollection 2022.
Depression is a disease with increasing prevalence worldwide, and it is necessary to develop a therapeutic agent with better efficacy than existing antidepressant drugs. Antidepressants that act on the glutamatergic nervous system, such as ketamine, have a rapid-onset antidepressant effect and are effective against treatment-resistant depression. However, because of the addictive potential of ketamine, alternative substances without psychological side effects are recommended. In particular, many natural compounds have been tested for their antidepressant effects. The antidepressant effects of (NS) have been tested in many studies, along with the various actions of NS on the glutamatergic system. Thus, it was expected that NS might have a rapid-onset antidepressant effect. To test the antidepressant potential, despair and anhedonic behaviors were measured after administering NS to mice exposed to social hierarchy stress (SHS), and biochemical changes in the prefrontal cortex and hippocampus were analyzed. NS reduced despair-like responses in the forced swim test and tail suspension test. Mice exposed to SHS showed depression-like responses such as increased despair, reduced hedonia, and an anxiety-like response in the novelty suppressed feeding test. NS, but not fluoxetine, improved those depression-like behaviors after acute treatment, and NBQX, an AMPA receptor blocker, inhibited the antidepressant-like effects of NS. The antidepressant-like effect of NS was related to enhanced phosphorylation of mTOR in the prefrontal cortex and dephosphorylation of GluR1 S845 in the hippocampus. Since NS has shown antidepressant-like potential in a preclinical model, it may be considered as a candidate for the development of antidepressants in the future.
抑郁症是一种在全球范围内患病率不断上升的疾病，因此有必要开发一种疗效优于现有抗抑郁药物的治疗剂。作用于谷氨酸能神经系统的抗抑郁药，如氯胺酮，具有快速起效的抗抑郁作用，对难治性抑郁症有效。然而，由于氯胺酮具有成瘾潜力，因此推荐使用无心理副作用的替代物质。特别是，许多天然化合物已被测试其抗抑郁作用。在许多研究中都测试了（NS）的抗抑郁作用，以及NS对谷氨酸能系统的各种作用。因此，预计NS可能具有快速起效的抗抑郁作用。为了测试其抗抑郁潜力，在对遭受社会等级压力（SHS）的小鼠给予NS后，测量其绝望和快感缺失行为，并分析前额叶皮质和海马体中的生化变化。NS减少了强迫游泳试验和悬尾试验中的绝望样反应。暴露于SHS的小鼠表现出抑郁样反应，如绝望增加、快感缺失减少以及在新奇抑制摄食试验中的焦虑样反应。急性治疗后，NS而非氟西汀改善了这些抑郁样行为，并且AMPA受体阻滞剂NBQX抑制了NS的抗抑郁样作用。NS的抗抑郁样作用与前额叶皮质中mTOR磷酸化增强以及海马体中GluR1 S845去磷酸化有关。由于NS在临床前模型中已显示出抗抑郁样潜力，因此未来可能被视为抗抑郁药开发的候选药物。
