Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; College of Integrative Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China; Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Shijiazhuang, Hebei, 050091, China.
Science and Technology Office, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China.
Eur J Pharmacol. 2024 Dec 5;984:177063. doi: 10.1016/j.ejphar.2024.177063. Epub 2024 Oct 18.
Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with brain inflammation and neuronal damage. Derived from the Aesculus chinensis Bunge fruit, escin has shown anti-inflammatory and neuroprotective effects. However, its potential as a treatment for MDD is unclear. This study investigates the antidepressant properties of escin using in vivo experimentation. The chronic unpredictable mild stress (CUMS) model was used to analyze the potential antidepressant effects and underlying mechanisms of escin. Wistar rats were exposed to CUMS for 35 consecutive days to induce MDD. The rats were then given either escin (1, 3, and 10 mg/kg) or fluoxetine (2 mg/kg) on a daily basis. Notably, escin significantly alleviated the depressive behaviors induced by CUMS, as evaluated through a series of behavioral assessments. Moreover, escin administration reduced TNF-α, IL-1β, and IL-6 levels in the hippocampus. It also decreased serum adrenal cortical hormone (ACTH) and corticosterone (CORT) levels while increasing 5-HT and Brain-derived neurotrophic factor (BDNF) levels in the CUMS rats, as measured by the enzyme-linked immunosorbent assay (ELISA). Pathological changes in the hippocampal regions were identified through Nissl staining, and Western blotting was used to quantify the protein levels of BDNF, TrkB, CREB, TLR4, MyD88, and NF-κB. Escin mitigated neuronal injury, elevated TrkB, BDNF, and CREB, and reduced TLR4, MyD88, and NF-κB protein levels in CUMS rats. The data from this study suggest that escin holds the potential for alleviating depression-like symptoms induced by CUMS. This effect may be mediated through the modulation of two signaling pathways, BDNF/TrkB/CREB and TLR4/MyD88/NF-κB.
重度抑郁症（MDD）是一种常见的精神疾病，与大脑炎症和神经元损伤有关。从七叶树果实中提取的七叶皂苷具有抗炎和神经保护作用。然而，其作为 MDD 治疗药物的潜力尚不清楚。本研究通过体内实验研究七叶皂苷的抗抑郁作用。采用慢性不可预测轻度应激（CUMS）模型分析七叶皂苷的潜在抗抑郁作用及其机制。将 Wistar 大鼠连续 35 天暴露于 CUMS 中以诱导 MDD。然后，大鼠每天给予七叶皂苷（1、3 和 10mg/kg）或氟西汀（2mg/kg）。值得注意的是，七叶皂苷显著缓解了 CUMS 诱导的抑郁行为，通过一系列行为评估进行评估。此外，七叶皂苷给药降低了海马体中的 TNF-α、IL-1β 和 IL-6 水平。通过酶联免疫吸附试验（ELISA）测量，它还降低了 CUMS 大鼠血清肾上腺皮质激素（ACTH）和皮质酮（CORT）水平，同时增加了 5-HT 和脑源性神经营养因子（BDNF）水平。通过尼氏染色鉴定海马区的病理变化，并用 Western blot 定量分析 BDNF、TrkB、CREB、TLR4、MyD88 和 NF-κB 的蛋白水平。七叶皂苷减轻了 CUMS 大鼠的神经元损伤，增加了 TrkB、BDNF 和 CREB 的水平，并降低了 TLR4、MyD88 和 NF-κB 的蛋白水平。本研究的数据表明，七叶皂苷具有缓解 CUMS 诱导的抑郁样症状的潜力。这种作用可能是通过调节 BDNF/TrkB/CREB 和 TLR4/MyD88/NF-κB 两条信号通路实现的。
