title: Metabolic profiles revealed synergistically antidepressant effects of lilies and Rhizoma Anemarrhenae in a rat model of depression.
abstract: Depression is a major cause of illness and disability. We applied untargeted metabolomics using mass spectrometry to identify metabolic signatures associated with depression in serum and explored the antidepressant effects of lilies and Rhizoma Anemarrhenae on an experimental model of chronic unpredictable mild stress (CUMS). Meanwhile metabolomics based on UHPLC-Q-TOF-MS was used to study the change in metabolites in CUMS rat serum and to evaluate the effects of Rhizoma Anemarrhenae and lilies (alone and in combination). Partial least squares-discriminant analysis identified 30 metabolites as decisive marker compounds that discriminated the CUMS rats and the control rats. The majority of these metabolites were involved in amino acid metabolism, the tricarboxylic acid cycle, and phosphoglyceride metabolism. The reliability of the metabolites was evaluated by the administration of lilies, Rhizoma Anemarrhenae, fluoxetine and the combination of lilies and Rhizoma Anemarrhenae to the CUMS rats. Behavior studies demonstrated that treatment with the combination of lilies and Rhizoma Anemarrhenae resulted in optimal antidepressant effects. The combination treatment was almost as effective as fluoxetine. Our results suggest that lilies and Rhizoma Anemarrhenae demonstrate synergistically antidepressant effects in CUMS via the regulation of multiple metabolic pathways. These findings provide insight into the pathophysiological mechanisms underlying CUMS and suggest innovative and effective treatments for this disorder.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.|Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Du
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Lai
authors.affiliation: Proteomics/Mass Spec Facility, Center for Functional Genomics, State University of New York at Albany, New York, USA.
authors.forename: Qishan
authors.initials: Q
authors.lastname: Lin
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Chai
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Ziyang
authors.identifier: http://orcid.org/0000-0003-0247-7251
authors.initials: Z
authors.lastname: Lou
mesh_terms: D031403:Anemarrhena; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D003863:Depression / Q000097:blood / Q000628:therapy*; D004195:Disease Models, Animal; D027762:Lilium; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome; D021241:Spectrometry, Mass, Electrospray Ionization
keywords: Rhizoma Anemarrhenae; antidepressant; chronic unpredictable mild stress (CUMS); lilies; metabolomic