Abstract
BackgroundDepression is a long-term complex psychiatric disorder, and its etiology remains largely unknown. Valeriana jatamansi Jones ex Roxb (V. jatamansi) is used in the clinic for the treatment of depression, but there are insufficient reports of its antidepressive mechanisms and a poor understanding of its endogenous substance-related metabolism. The objective of this study was to identify biomarkers related to depression in serum samples and evaluate the antidepressive effects of the iridoid-rich fraction of V. jatamansi (IRFV) in a chronic unpredictable mild stress (CUMS) mouse model.MethodsHere, CUMS was used to establish a mouse model of depression. Behavioral and biochemical indicators were investigated to evaluate the pharmacodynamic effects. A comprehensive serum metabolomics study by nuclear magnetic resonance (NMR) approach was applied to investigate the pharmacological mechanism of IRFV in CUMS mouse. Subsequently, we used multivariate statistical analysis to identify metabolic markers, such as principal component analysis (PCA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA), to distinguish between the CUMS mouse and the control group.ResultsAfter IRFV treatment, the immobility time, sucrose preference, and monoamine neurotransmitter were improved. PCA scores showed clear differences in metabolism between the CUMS group and control group. The PLS-DA or OPLS-DA model exhibited 26 metabolites as biomarkers to distinguish between the CUMS mice and the control mouse. Moreover, IRFV could significantly return 21 metabolites to normal levels.ConclusionThe results confirmed that IRFV exerted an antidepressive effect by regulating multiple metabolic pathways, including the tricarboxylic acid cycle, the synthesis of neurotransmitters, and amino acid metabolism. These findings provide insights into the antidepressive mechanisms of IRFV.
Highlights
Depression, a common mental illness characterized by sadness, severely affects a patient's quality of life (Gong et al, 2019)
The 1st, 2nd, 3rd, and 4th weeks after chronic unpredictable mild stress (CUMS) intervention and two weeks after drug administration, the body weights of all mice treated with CUMS were slightly lower than the mice in the control group
The body weights in the control group showed a natural increase, while the body weights in the iridoid-rich fraction of V. jatamansi (IRFV) dosage and Flu groups significantly increased compared to the model group (p < 0.05 or p < 0.01)
Summary
Depression, a common mental illness characterized by sadness, severely affects a patient's quality of life (Gong et al, 2019). The etiology of depression is assumed to be associated with genetics, the noradrenergic, dopaminergic, and serotoninergic systems, and stress (Drago et al, 2011). One suffering from depression would have been primarily treated by synthetic antidepressants with emerging adverse effects, such ascardiotoxicity, hypertensive crisis, and sleep disorders (Read et al, 2014). Valeriana jatamansi Jones ex Roxb (V. jatamansi) is used in the clinic for the treatment of depression, but there are insufficient reports of its antidepressive mechanisms and a poor understanding of its endogenous substance-related metabolism. The objective of this study was to identify biomarkers related to depression in serum samples and evaluate the antidepressive effects of the iridoid-rich fraction of V. jatamansi (IRFV) in a chronic unpredictable mild stress (CUMS) mouse model
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