Chaihu-Shugan-San and its component ferulic acid, derived from medicinal plants, effectively addresses depression, endothelial dysfunction, and gastrointestinal dysregulation induced by acute forced swimming.
The researchers created a depression-like model in rats using acute forced swimming (AFS) and an oxidative stress model in endothelial cells using hydrogen peroxide treatment. They then studied the effects of Chaihu-Shugan-San (CSS) and ferulic acid (FA) on major depressive disorder, endothelial dysfunction, and gastrointestinal dysregulation evident in the rats and oxidative stress levels in the endothelial cells. The tests involved biochemical assays, behavior studies, and staining techniques. Meanwhile, an intricate analysis of transcriptomics, proteomics, and phosphoproteomics data was completed to discover the underlying mechanisms.
The results display that CSS and FA notably alleviate AFS-induced abnormalities such as gastric emptying and intestinal transit in rats, disrupt symptoms of depression, rectify endothelial and gastrointestinal dysfunctions, as well as control inflammation and oxidative stress-related biomarker levels. Additionally, it was revealed that FA can alter oxidative stress and endothelial function in endothelial cells. A multi-omics analysis shed light on multiple oxidative stress-related pathways involved, such as the Ghrl-Edn1/Mecp2/P-mTOR/Vegfa-associated oxidative stress signaling pathway. This particular pathway is fundamental in tackling AFS-induced multimorbidity, superseding the traditional disease-specific focus.
