The traditional Chinese medicine, Chaihu-Shugan-San, alleviates post-stroke depression in mice through exosome-mediated signaling and regulation of miR-146.
The active compounds in Chaihu-Shugan-San (CSS) were identified from rat serum using liquid chromatography-mass spectrometry and analyzed via network pharmacology. In laboratory conditions, an oxygen-glucose deprivation/reperfusion BV2 microglia model was used to gauge the effects of CSS-containing serum. Exosomes from this model were isolated and analyzed using transmission electron microscopy and nanoparticle tracking analysis. In live test, a photothrombotic stroke model alongside chronic unpredictable mild stress induced post-stroke depression in mice. Behavior assessments, histological analysis and different test methods were used to measure key protein and miR-146 expressions in the mice's hippocampus.
The CSS treatment was found to notably relieve depressive-like behaviors in the mouse model. Increased sucrose preference, reduced immobility and enhanced exploratory activity were observed in mice treated with a high dose of CSS. The treatment improved brain tissue integrity, alleviated neuronal damage, and reduced neuroinflammation. It was found that CSS increased the expression of microglia-derived exosomes in the hippocampus which carried miR-146. Moreover, this treatment also adjusted the expression of miR-146 isoforms by reversing abnormal miRNA expression. This indicates a potential mechanism for its neuroprotective effects. CSS also successfully reduced key inflammatory cytokines while rejuvenating angiogenic factors. Notably, the calcium signaling pathway was also implicated.
