Effect of Cryptotanshinone on BDNF/TrkB Pathway in Hippocampus of Chronic Stress-induced Depression Rats

Abstract

Background: Cryptotanshinone (CTS) is a monomer possessing a diverse array of pharmacological properties, primarily derived from Salvia miltiorrhiza. CTS was examined for its impact on rats with depression subjected to chronic unpredictable mild stress (CUMS) in this study. Materials and methods: Depression-like behavior of rats was established by isolated feeding combined with CUMS for 28 days, with CTS (7/14/21 mg/kg) or fluoxetine (5 mg/kg) administered once daily during this time. A comprehensive evaluation was performed, including body weight assessment, sucrose preference test, forced swimming test, and open field test. Hematoxylin-eosin staining was conducted to detect pathological changes in hippocampal CA1 neurons. Western blot analysis was employed to assess the brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), Ras-related C3 botulinum toxin substrate 1 (Rac1), and Cofilin expression levels in the hippocampus. Results: The depression rat model was successfully constructed. CTS can significantly improve impaired neurons in the hippocampal CA1 area, depression-like behaviors, and weight loss in CUMS-induced rats. Moreover, CTS reversed the down-regulation of BDNF/TrkB and Rac1/Cofilin in the CUMS-induced rats’ hippocampus. Conclusion: CTS demonstrates the therapeutic potential for depression by improving depression-like behaviors and ameliorating impaired neurons in the hippocampal CA1 area, and the mechanisms may involve the up-regulation of BDNF/TrkB and related signaling proteins Rac1/Cofilin.