Xingshen Jieyu Decoction ameliorates post-stroke depression by modulating proBDNF/BDNF signaling via PI3K/Akt pathway

作者：Xiang Chen, Wei Zhao, Zhenzhen Hou, Jian‐Yong Zhu, Zeyu Ren, L. Li, Honglin Wang, Yang Yang, Yu Lou, Hongpu Song, Yue Zhu, Zhenxiang Han · 发表于：Journal of Ethnopharmacology · 年份：2025 · DOI：10.1016/j.jep.2025.120884 · 被引用次数：2 · 研究领域：Traditional Chinese Medicine Analysis、Tryptophan and brain disorders、Metabolomics and Mass Spectrometry Studies

ETHNOPHARMACOLOGICAL RELEVANCE: Xingshen Jieyu Decoction (XSJY), a traditional Chinese herbal formula, is well known for alleviating post-stroke depression(PSD) symptoms and exerting neuroprotective effects. It has been clinically applied for PSD treatment. However, the underlying mechanisms remain insufficiently understood. AIM OF THE STUDY: To investigate the antidepressant effects and molecular mechanisms of XSJY in a PSD rat model, focusing on apoptosis regulation and PI3K/Akt and proBDNF/BDNF signaling pathways. MATERIAL AND METHODS: The chemical profile of XSJY was characterized by HPLC/ESI-MS. A validated PSD model was established by combing middle cerebral artery occlusion(MCAO) with chronic unpredictable mild stress(CUMS). Rats received XSJY at low or high doses(18.72 or 37.44 g/kg/day) or sertraline(5.142 mg/kg/day) for two weeks. Behavior outcomes(body weight, sucrose preference test[SPT], forced swim test[FST], and hippocampal apoptosis(TUNEL staining) were assessed. Western blotting was performed to evaluate PI3K/Akt activity, caspase-3/9,proBDNF, BDNF, p75NTR, TrkB, neurofilament light chain(NF-L) and neurofilament heavy chain(NF-H) expression. To determine pathway specificity, the PI3K inhibitor LY294002 was co-administered. RESULTS: Forty main compounds were identified in XSJY by HPLC/ESI-MS. XSJY significantly alleviated depressive-like phenotypes, as evidenced by reduced immobility in the FST and increased sucrose preference. It also markedly attenuated hipp...