Faculty of Medicine, Department of Pharmacology, Kütahya Health Sciences University, Evliya Çelebi Yerleşkesi, Kütahya, 43000, Türkiye.
Faculty of Engineering and Natural Sciences, Department of Basic Sciences of Engineering, Kütahya Health Sciences University, Evliya Çelebi Yerleşkesi, Kütahya, 43000, Türkiye.
Metab Brain Dis. 2024 Dec;39(8):1523-1541. doi: 10.1007/s11011-024-01416-6. Epub 2024 Aug 22.
Depression is a mental disorder characterised by persistent low mood, anhedonia and cognitive impairment that affects an estimated 3.8% of the world's population, including 5% of adults. Peganum harmala L. (P. harmala) is a medicinal plant and has been reported to be effective against Alzheimer's disease, Parkinson's disease and depression. The present study was aimed to evaluate the behavioral and pharmacological effects of P. harmala seed extract in rats exposed to chronic unpredictable mild stress (CUMS) in vivo and to investigate the mechanism of action. CUMS-exposed rats were treated with P. harmala extract (75 and 150 mg/kg, i.p.) for 2 weeks. HPLC analysis was used to determine the concentration of harmaline and harmine alkaloids in the extract. Heavy metal analysis in seeds was performed by ICP-MS. Our results showed that P. harmala at the dose of 150 mg/kg significantly reduced the depressive-like behaviors in CUMS-exposed rats, as evidenced by increased sucrose consumption in the sucrose preference test (SPT), decreased immobility time in the forced swim test (FST) and plasma corticosterone levels, increased the time spent in open arms in the elevated plus maze (EPM), and improved memory and learning in the passive avoidance test (PAT). In addition, P. harmala decreased monoamine oxidase-A (MAO-A) levels, and increased serotonin (5-HT), dopamine (DA), and noradrenaline (NA) levels in the brains of rats exposed to CUMS. P. harmala decreased the expression of the pro-inflammatory transcription factor nuclear factor-κB (NF-κB), and increased the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) in rat brain. Furthermore, P. harmala improved brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) protein expression in rat brain. In conclusion, P. harmala at a dose of 150 mg/kg is more effective in preventing depressive-like behavior in CUMS-exposed rats by improving neurotransmitter levels, reducing oxidative stress, suppressing neuroinflammation and activating the BDNF/TrkB pathway, all of which are important in the pathogenesis of depression.
抑郁症是一种以持续性情绪低落、快感缺失和认知障碍为特征的精神障碍，据估计影响了全球 3.8%的人口，包括 5%的成年人。骆驼蓬（Peganum harmala L.）是一种药用植物，据报道对阿尔茨海默病、帕金森病和抑郁症有效。本研究旨在评估骆驼蓬种子提取物对慢性不可预测轻度应激（CUMS）暴露大鼠的行为和药理学作用，并探讨其作用机制。CUMS 暴露大鼠用骆驼蓬提取物（75 和 150mg/kg，ip）治疗 2 周。采用 HPLC 分析测定提取物中哈尔明和哈尔碱的浓度。采用 ICP-MS 进行种子重金属分析。我们的结果表明，骆驼蓬在 150mg/kg 剂量下可显著减轻 CUMS 暴露大鼠的抑郁样行为，表现为蔗糖偏好试验（SPT）中蔗糖消耗增加、强迫游泳试验（FST）和血浆皮质酮水平中不动时间减少、高架十字迷宫（EPM）中开放臂时间增加，以及被动回避试验（PAT）中记忆和学习能力提高。此外，骆驼蓬降低了 CUMS 暴露大鼠大脑中单胺氧化酶-A（MAO-A）的水平，并增加了 5-羟色胺（5-HT）、多巴胺（DA）和去甲肾上腺素（NA）的水平。骆驼蓬降低了促炎转录因子核因子-κB（NF-κB）的表达，并增加了大鼠大脑中的抗氧化核因子红细胞 2 相关因子 2（Nrf2）。此外，骆驼蓬改善了大鼠大脑中脑源性神经营养因子（BDNF）和原肌球蛋白受体激酶 B（TrkB）蛋白的表达。总之，骆驼蓬在 150mg/kg 剂量下更有效地预防 CUMS 暴露大鼠的抑郁样行为，通过改善神经递质水平、减少氧化应激、抑制神经炎症和激活 BDNF/TrkB 通路，所有这些都在抑郁症的发病机制中起重要作用。
