PMID:
Phytomedicine. 2024 Jun ;128:155433. Epub 2024 Feb 7. PMID: 38547621
Abstract Title:
Echinacoside ameliorates post-stroke depression by activating BDNF signaling through modulation of Nrf2 acetylation.
Abstract:
BACKGROUND: Post-stroke depression (PSD) affects approximately one-third of stroke survivors, leading to adverse outcomes in rehabilitation, reduced quality of life, and increased mortality rates. Despite these implications, the underlying causes of PSD remain unclear, posing challenges for prevention and treatment. Echinacoside (ECH), a natural compound with known neuroprotective and antidepressant properties, holds significant therapeutic potential for PSD. However, the precise mechanism of its action remains unknown.PURPOSE: To unravel the specific mechanism through which ECH alleviates PSD by exploring the intricate interplay between ECH and Nrf2, as well as its impact on the BDNF/TrkB signaling axis.STUDY DESIGN AND METHODS: A rat PSD model was established though middle cerebral artery occlusion coupled with chronic unpredictable mild stress, followed by ECH treatment. The rats' depressive state was evaluated using the sucrose preference test and force swimming test. Brain damage was assessed through TTC staining, Nissl staining, and TUNEL assay. The multifaceted mechanism of ECH in PSD was investigated using immunofluorescence, immunohistochemistry, RT-qPCR, dual-luciferase assay, and western blotting. Additionally, the interaction between ECH and Nrf2 was explored through molecular docking and microscale thermophoresis.RESULTS: Our findings unveiled a novel facet of ECH action, demonstrating its unique ability to upregulate Nrf2 through acetylation within the hippocampus of PSD-affected rats (p
