LC-MS/MS based studies on the anti-depressant effect of hypericin in the chronic unpredictable mild stress rat model

St John׳s Wort (Hypericum perforatum, SJW) is a widely used herbal medicine in western countries but also an important Uygur drug in China. Hypericin (HY) is the main components in SJW extracts, which is used to treat fatigue, weakness, and mild depression. The aim of this study was to investigate the anti-depression effects of HY on chronic unpredictable mild stress (CUMS) model rats and identify the possible mechanisms.

In this study, the protective effects of HY on CUMS-induced depression in rats were investigated by using a combination of behavioral assessments and urinary metabolites analysis. Urinary metabolites analyses were performed using LC-MS/MS in conjunction with principal components analysis (PCA) after oral administration of either HY or Venlafaxine (VF) for 27 days. During the procedure of experiment, food consumption, body weight, adrenal gland, thymus and spleen indices, behavior scores, sucrose consumption, and stress hormone levels were measured.

Changes in the classic behavioral tests and pharmacological biochemical indices reflected that HY alleviated the symptoms of depression in a shorter period than VF, which was used as positive control for antidepression. Metabolites analysis of urine revealed that HY affected excitatory amino acids and monoamine neurotransmitter metabolites. Remarkably, urinary valine was increased remarkably by HY, even much higher than CUMS group. These results provide important mechanistic insights into the protective effects of HY against CUMS-induced depression and metabolic dysfunction.

As the most important active ingredient in SJW extracts, HY possesses the better protective effect against CUMS-induced depression symptoms and metabolic disturbances.