Escin ameliorates CUMS-induced depressive-like behavior via BDNF/TrkB/CREB and TLR4/MyD88/NF-κB signaling pathways in rats

• Published in: European journal of pharmacology 2024-12, Vol.984, p.177063, Article 177063
• Main Authors: Liu, Fengjiao, Jia, Yaxin, Zhao, Liwei, Xiao, Li-na, Cheng, Xizhen, Xiao, Yingying, Zhang, Ying, Zhang, Yuling, Yu, Huimin, Deng, Qiao-en, Zhang, Yuanyuan, Feng, Yimeng, Wang, junfang, Gao, Yonggang, Zhang, Xuan, Geng, Yunyun
• Format: Article
• Language: English
• Subjects: Animals; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; BDNF/TrkB/CREB; Behavior, Animal - drug effects; Behavioral tests; Brain-Derived Neurotrophic Factor - metabolism; Cyclic AMP Response Element-Binding Protein - metabolism; Depression - drug therapy; Depression - etiology; Depression - metabolism; Disease Models, Animal; Escin; Escin - pharmacology; Escin - therapeutic use; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Major depressive disorder; Male; Membrane Glycoproteins - metabolism; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B - metabolism; Rats; Rats, Wistar; Receptor, trkB - metabolism; Signal Transduction - drug effects; Stress, Psychological - complications; Stress, Psychological - drug therapy; TLR4/MyD88/NF-κB; Toll-Like Receptor 4 - metabolism
• ISSN: 0014-2999; 1879-0712; 1879-0712
• DOI: 10.1016/j.ejphar.2024.177063

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. •Escin treatment alleviated depression-like behaviors in CUMS rats.•Escin treatment reduced CUMS-induced inflammation in the hippocampus.•Escin treatment attenuated neuronal damage induced by CUMS.•Escin decreased pro-inflammatory factor expression via the TLR4/MyD88/NF-κB pathway.•Escin relieves depressive behavior by modulating the BDNF/TRKB/CREB signaling pathway.