Sanggenon C ameliorates chronic stress induced depressive behaviors

Abstract

Purpose: To investigate the effect of Sanggenon C on depression caused by chronic unpredictable mild stress (CUMS) in Wistar rats.
 Methods: The anti-depression effect of Sanggenon C was assessed using a forced swimming test and sucrose preference assay. Open-field test was performed to measure CUMS-induced locomotor alteration while histological analyses of the hippocampus and cortex were performed using hematoxylin and eosin (H & E) stains. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was employed to evaluate apoptosis. In addition, expressions of Bax, Bcl-2, cleaved caspase-3, LC3, Beclin, P62 and brain-derived neurotrophic factor (BDNF), as well as phosphorylation level of AMP-activated protein kinase (AMPK) were evaluated by Western blot.
 Results: Sanggenon C significantly elevated sucrose preference, reduced immobility time in the forced swimming test, and enlarged squares crossed and rearing times in open-field CUMS rats (p < 0.05). Sanggenon C ameliorated nuclear shrinkage and damage in the hippocampus or cortex. Sanggenon C also regulated the expression of apoptosis-related proteins (Bax, Bcl-2 and cleaved caspase-3), as well as autophagy-associated molecules (LC3, Beclin and p62). Furthermore, Sanggenon C enhanced the expression of BDNF and phosphorylation of AMPK.
 Conclusion: Sanggenon C inhibits apoptosis, induces neuronal autophagy, and improves depressive behavior and neuroprotection via activation of AMPK pathway in CUMS rats. However, further research is needed to fully understand the clinical significance of Sanggenon C-mediated AMPK activation in different cellular contexts as potential drug targets.