title: Metabonomic identification of the effects of the Zhimu-Baihe saponins on a chronic unpredictable mild stress-induced rat model of depression.
abstract: The herbal pair Zhimu-Baihe (Zhimu: Anemarrhena asphodeloides; Baihe: Lilium brownii var. viridulum) is a traditional Chinese medicament used for the treatment of depression. However, the relevant mechanisms of action has not been clarified. This study investigated the anti-depressant activity of the total saponins from Zhimu and Baihe and the mechanisms underlying using a chronic unpredictable mild stress (CUMS)-induced rat model of depression. High performance liquid chromatography with electrochemical detection (HPLC-ECD) was applied to determine the levels of three monoamine neurotransmitters, 5-hydroxytryptamine (5-HT), noradrenaline (NE) and dopamine (DA), in the rat hippocampus. Optimized pretreatment of samples and mass spectrometry conditions were used to analyse the metabonomic profile of the hippocampus. The 5-HT and NE levels in the CUMS group were reduced compared with the control group, whereas all groups had similar DA levels. The metabonomic profile of the hippocampus revealed 32 differential metabolites between the CUMS and control group, among which 18 metabolites were significantly recovered in the Anemarrhena saponins and Lilium saponins (AL) combination intervention group. These results suggested an anti-depressant effect of AL. Moreover, 24 metabolites in AL group were better recovered compared with the Anemarrhena saponins (AS) or Lilium saponins (LS) intervention groups, suggesting a synergetic effect of AS and LS in the treatment of depression. The anti-depressant effect might be related to the regulation of several metabolic pathways, including monoamine neurotransmitter synthesis (especially 5-HT and NE), and amino acid, fatty acid, and phospholipid metabolism in rats.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Du
authors.affiliation: SZYY Group Pharmaceutical Limited, Jiangsu 225500, China.
authors.forename: Keqing
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Proteomics/Mass Spectrometry Facility, Center for Functional Genomics, State University of New York at Albany, NY 12144, USA.
authors.forename: Qishan
authors.initials: Q
authors.lastname: Lin
authors.affiliation: SZYY Group Pharmaceutical Limited, Jiangsu 225500, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Ma
authors.affiliation: SZYY Group Pharmaceutical Limited, Jiangsu 225500, China.
authors.forename: Baokang
authors.initials: B
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: dongxinsmmu@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: ziyanglou@163.com.
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Lou
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D003863:Depression / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D055432:Metabolomics; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012503:Saponins / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D004365:Drugs, Chinese Herbal; D012503:Saponins; C060637:zhi-mu saponin; C000618711:zhimu-baihe; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine
keywords: Chronic unpredictable mild stress; Hippocampus; Intervention; Metabonomics; Zhimu-Baihe saponins