Chemical component analysis of the traditional Chinese medicine Guipi Tang and its effects on major depressive disorder at molecular level.

Ethnopharmacological relevance: Guipi Tang (GPT) is a widely used traditional Chinese medicine that is used to treat major depressive disorder. However, the molecular mechanisms of its effects remain unclear. Aim of the study: This study aimed to investigate the antidepressant-like effects of GPT and explore its underlying molecular mechanisms. Materials and methods: Male Sprague-Dawley rats were subjected to a chronic unpredictable mild stress (CUMS) procedure and treated with various doses of GPT, with fluoxetine treatment as a positive control. Behavioural tests (including sucrose preference test, novelty-suppressed feeding test, open-field test and forced swim test), terminal deoxynucleotidyl transferase dUTP nick end labeling and enzyme-linked immunosorbent assay were conducted. The levels of Bax, Bcl-2, cleaved caspase-3, PI3K, p-PI3K, AKT, p-AKT, BDNF, TrkB and CREB or p-CREB were assessed at the protein level using western blotting or immunofluorescence. Results: GPT consists of mainly known drugs, such as liquiritin and ginsenosides. It reversed depressive behaviours and decreased cell apoptosis in the hippocampi of CUMS rats. It significantly upregulated the protein level of Bax, p-Akt, p-PI3K, BDNF, TrkB and p-CREB and downregulated the level of cleaved caspase-3 and Bcl-2. Conclusions: GPT had anti-depressive activity as indicated by the amelioration of depression-like behaviour and the inhibition of hippocampal neuronal apoptosis in CUMS rats. This inhibition was mediated partly by modulating the PI3K/Akt and/or BDNF/TrkB/CREB pathway, in which, glycosides, the main components of GPT, might be involved.