A comparative study of the main constituents and antidepressant effects of raw and vinegar-baked Bupleuri Radix in rats subjected to chronic unpredictable mild stress

Bupleuri Radix (BR) is a traditional Chinese medicine (TCM) widely used in Asian nations, which originates from Bupleurum chinense DC or Bupleurum scorzonerifolium Willd. It can be baked with vinegar to obtain vinegar-baked Bupleuri Radix (VBBR). It has been reported that VBBR exhibits more potential activity for relieving the effects of a depressed liver than BR. However, the antidepressant effects and underlying pharmacological mechanisms of BR and VBBR remain unclear. The present study identified the main chemical compositions in BR and VBBR. Furthermore, behavioral studies along with biochemical assessments, as well as 1H NMR analysis of the hippocampus and liver were employed to systematically assess the pathology of depression and therapeutic effects of BR and VBBR using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. Behavioral studies demonstrated that treatment with VBBR resulted in better antidepressant effects than BR. And VBBR significantly regulated the levels of neurotransmitters in the hippocampus and frontal cortex. Additionally, twelve and ten metabolites from the hippocampus and liver were identified as potential biomarkers associated with depression. Such biomarkers are primarily involved in energy metabolism, amino acid metabolism, glycolysis, inositol phosphate metabolism, lipid metabolism and the TCA cycle. The results presented here showed that VBBR significantly reversed the pathological process of CUMS-induced depression, partially via regulation of the disturbed metabolic pathways. The comparative study facilitated a better understanding of the antidepressant mechanisms of BR and VBBR.