Develop a stepwise integrated method to screen biomarkers of Baihe‐Dihuang Tang on the treatment of depression in rats applying with composition screened, untargeted, and targeted metabolomics analysis

Abstract

Baihe‐Dihuang Tang is a commonly prescribed remedy for depression. In this study, component screening with untargeted and targeted metabolomics was used to identify potential biomarkers for depression in chronic unpredictable mildly stressed rats. Using this novel identification method, the screening of organic acids, lily saponins, iridoids, and other ingredients formed the basis for subsequent metabolomics research. Baihe‐Dihuang Tang supplementation in chronic unpredictable mild‐stress‐induced depression models, increased their body weight, sucrose preference, brain‐derived neurotrophic factor deposition, and spatial exploring. Untargeted metabolomics revealed that Baihe‐Dihuang Tang exerts its antidepressant effects by regulating the levels of lipids, organic acids, and its derivatives, and benzenoids in the brain, plasma, and urine of the depressed rats. Moreover, it also modulates the d‐glutamine and d‐glutamate metabolism and purine metabolism. Targeted metabolomics demonstrated significant reduction in l‐glutamate levels in the brains of depressed rats. This could be a potential biomarker for depression. Baihe‐Dihuang Tang alleviated depression by regulating the levels of l‐glutamate, xanthine, and adenine in the brains of depressed rats. Together, these findings conclusively established the promising therapeutic effect of Baihe‐Dihuang Tang on depression and also unraveled the underlying molecular mechanism of its potential antidepressant function.

Research progress on classical traditional Chinese medicine formula Baihe Zhimu (Lilium lancifolium bulb and Anemarrhena asphodeloides rhizome) decoction in the treatment of depression

“…There are research results demonstrated that mangiferin possessed antidepressant and anti-anxiety properties due to its ability to attenuate IL-1β level and oxidative stress (including increasing reduced glutathione concentration and related enzyme activities) evoked by intraperitoneal administration of lipopolysaccharide [ 94 ]. Gu screened out Lilium lancifolium bulb saponins through untargeted and targeted metabolomics, found that it can not only effectively increase BDNF deposition but also modulates the glutamine and glutamate metabolism, restoring reduced glutamate levels in the brains of depressed rats; revealed the glutamatergic system was involved in the antidepressant activity of Lilium lancifolium bulb saponins (LS) [ 102 , 103 ]. Du used the CUMS rat depression model and found that Anemarrhena saponins (AS) could significantly restore monoamine neurotransmitter levels in the hippocampus of depressed rats, the metabonomic profile revealed the anti-depressant effect might be related to the regulation of several metabolic pathways, including amino acid, fatty acid, and phospholipid metabolism in rats, suggesting a synergetic effect of AS and LS in the treatment of depression [ 103 ].…”