Department of Neurosurgery, The Sixth People's Hospital of Nantong, Nantong, Jiangsu, China.
Department of Burns and Plastic Surgery, Taizhou People's Hospital, The Fifth Affiliated Hospital of Nantong University, Taizhou, Jiangsu, China.
Int J Neuropsychopharmacol. 2018 Aug 1;21(8):764-776. doi: 10.1093/ijnp/pyy028.
Current antidepressants in clinical use always take weeks or even months to exert full therapeutic effects, and sometimes have serious side effects. Thus, it is very necessary to develop novel antidepressants with better efficacy and fewer adverse effects. The present study focused on investigating the antidepressant potential of matrine and its possible mechanisms of action.
The forced swim test, tail suspension test, and chronic unpredictable mild stress model of depression were used to reveal the antidepressant-like effects of matrine on mice. Western blotting, immunohistochemistry, and lentivirus were further used together to explore the antidepressant mechanism of matrine.
It was found that matrine exhibited significant antidepressant actions in the forced swim test and tail suspension test without affecting the locomotor activity of mice. Chronic matrine administration fully reversed the chronic unpredictable mild stress-induced depressive-like symptoms in forced swim test, tail suspension test, and sucrose preference test. After that, western blotting analysis revealed that chronic matrine treatment restored the decreasing effects of chronic unpredictable mild stress on the PI3K/Akt/mammalian target of rapamycin signaling in hippocampus, but not prefrontal cortex. Furthermore, pharmacological and genetic blockade of the PI3K/Akt/mammalian target of rapamycin signaling in hippocampus abolished the antidepressant actions of matrine on mice.
Taken together, matrine produces antidepressant-like effects on mice via promoting the hippocampal PI3K/Akt/ mammalian target of rapamycin signaling.
目前临床使用的抗抑郁药通常需要数周甚至数月才能发挥完全的治疗效果，而且有时会产生严重的副作用。因此，开发疗效更好、副作用更少的新型抗抑郁药是非常必要的。本研究旨在研究苦参碱的抗抑郁作用及其可能的作用机制。
采用强迫游泳试验、悬尾试验和慢性不可预知性轻度应激抑郁模型，揭示苦参碱对小鼠的抗抑郁样作用。进一步采用Western blot、免疫组织化学和慢病毒共转染技术，探讨苦参碱的抗抑郁机制。
发现苦参碱在强迫游泳试验和悬尾试验中表现出显著的抗抑郁作用，而不影响小鼠的运动活性。慢性苦参碱给药完全逆转了慢性不可预知性轻度应激在强迫游泳试验、悬尾试验和蔗糖偏好试验中引起的抑郁样症状。随后，Western blot 分析显示，慢性苦参碱处理恢复了慢性不可预知性轻度应激对海马 PI3K/Akt/哺乳动物雷帕霉素靶蛋白信号的下调作用，但对前额叶皮质没有影响。此外，在海马中阻断 PI3K/Akt/哺乳动物雷帕霉素靶蛋白信号的药理学和遗传学阻断消除了苦参碱对小鼠的抗抑郁作用。
综上所述，苦参碱通过促进海马 PI3K/Akt/哺乳动物雷帕霉素靶蛋白信号产生抗抑郁样作用。
