Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles

Abstract

The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS) may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS) (with depression) and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC-Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR) produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future.

Xiao‐Yao‐San Formula Improves Cognitive Ability by Protecting the Hippocampal Neurons in Ovariectomized Rats

“…ey also reported that Bupleuri Radix, the principal antidepressant component, could produce more toxic effects in the liver or kidney of healthy rats than in rats with chronic unpredictable mild stress. e toxic effects were associated with increased bile acid concentration, facilitation of lysine degradation, and metabolic disruption of sphingolipid, glycerophospholipid, and fatty acids [60,64]. is result was corroborated in a recent metabolomic study of patients with depression.…”

Enhanced pseudotargeted analysis using a segment data dependent acquisition strategy by liquid chromatography–tandem mass spectrometry for a metabolomics study of liquiritin in the treatment of depression

“…Terpenoid backbone biosynthesis was associated with energy metabolism [5], and the disturbances of energy metabolism might be generated by resisting the unpredictable stressors in depression. Lysine degradation was also reported to be related to depression [26].…”

Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis

“…The cells were then treated with 1% DMSO or SSc (10-20 μg/mL) followed by measurement of the cellular HBV DNA by real-time PCR Despite many advantages of SSc have been found, some issues about SSc's anti-HBV activity are still unsolved. For example, while studies from Tajiri H et al showed that the prescription of 'Xiao-Chai-Hu-Tang' promoted clearance of HBeAg in children with chronic HBV infection, the toxicity of Radix Bupleuri were also be observed [51,52]. Although SSc has been proved with effective anti-HBV activity and little toxicity, the conclusion summarized here was based on in vitro experiments.…”