title: Determination of depression biomarkers in rat plasma by liquid chromatography-mass spectrometry for the study of the antidepressant effect of Zhi-Zi-Hou-Po decoction on rat model of chronic unpredictable mild stress.
abstract: Zhi-Zi-Hou-Po decoction (ZZHPD), a traditional Chinese medicine (TCM) formula, has been used for treatment of depressive-like symptoms for centuries. However, studies of its antidepressant effect and mechanism are challenging, owing to the complex pathophysiology of depression and complexity of ZZHPD with multiple constituents acting on different metabolic pathways. The present study was designed to develop a liquid chromatography-mass spectrometry (LC-MS) method for simultaneous determination of depression biomarkers: tryptophan (Trp), phenylalanine (Phe), tyrosine (Tyr), indole-3-acetic acid (IAA), hippuric acid (HA), phenaceturic acid (PA), creatinine (Cr), glutamic acid (Glu), succinic acid (SA) and γ-aminobutyric acid (GABA), as well as to study the antidepressant effect and potential mechanism of ZZHPD based on holistic view of an organism. The analysis was performed on a CAPCELL PAK C18 column with methanol and 0.01% formic acid in water using gradient elution. The method showed a good linearity (r(2)>0.99) with the other validation parameters were within acceptance range. The results demonstrated Trp, Phe, Tyr, IAA, HA, Cr, Glu and SA levels were significant lower in model group, while PA and GABA were significant higher than those in control group. The rats with ZZHPD treatment showed a tendency of bringing the levels of all these biomarkers to normal except Cr and Glu. It could be a powerful manner to provide mechanistic insights into the therapeutic effects of complex prescriptions and further understand pathophysiology of depression to assist in clinical diagnosis.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xing
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Medicine and Health Sciences, University of North Dakota, 501 North Columbia Rd., Grand Forks, ND 58202 USA.
authors.forename: Ruowen
authors.initials: R
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Gu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Shi
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Kaishun
authors.initials: K
authors.lastname: Bi
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: cxh_syphu@hotmail.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D003863:Depression / Q000097:blood* / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000494:pharmacology; D039823:Iridoids / Q000008:administration & dosage* / Q000494:pharmacology; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D039823:Iridoids; C581916:Zhi-Zi-Hou-Pu decoction
keywords: Chronic unpredictable mild stress; Depression biomarkers; Liquid chromatography-mass spectrometry; Rat plasma; Zhi-Zi-Hou-Po decoction