title: Role of Bai-Shao towards the antidepressant effect of Chaihu-Shu-Gan-San using metabonomics integrated with chemical fingerprinting.
abstract: Chaihu-Shu-Gan-San (CSGS) is a classical traditional Chinese medicine formula for the treatment of depression. As one of the single herbs in CSGS, Bai-Shao displayed antidepressant effect. In order to explore the role of Bai-Shao towards the antidepressant effect of CSGS, the metabolic regulation and chemical profiles of CSGS with and without Bai-Shao (QBS) were investigated using metabonomics integrated with chemical fingerprinting. At first, partial least squares regression (PLSR) analysis was applied to characterize the potential biomarkers associated with chronic unpredictable mild stress (CUMS)-induced depression. Among 46 differential metabolites found in the ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) and (1)H NMR-based urinary metabonomics, 20 were significantly correlated with the preferred sucrose consumption observed in behavior experiments and were considered as biomarkers to evaluate the antidepressant effect of CSGS. Based on differential regulation on CUMS-induced metabolic disturbances with CSGS and QBS treatments, we concluded that Bai-Shao made crucial contribution to CSGS in the improvement of the metabolic deviations of six biomarkers (i.e., glutamate, acetoacetic acid, creatinine, xanthurenic acid, kynurenic acid, and N-acetylserotonin) disturbed in CUMS-induced depression. While the chemical constituents of Bai-Shao contributed to CSGS were paeoniflorin, albiflorin, isomaltopaeoniflorin, and benzoylpaeoniflorin based on the multivariate analysis of the UPLC-Q-TOF/MS chemical profiles from CSGS and QBS extracts. These findings suggested that Bai-Shao played an indispensable role in the antidepressant effect of CSGS.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Chang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Jia
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Hongwu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Junshan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. Electronic address: zmzou@implad.ac.cn.
authors.forename: Zhongmei
authors.initials: Z
authors.lastname: Zou
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use / Q000652:urine; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D029596:Paeonia / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry*; D025341:Principal Component Analysis; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C497000:chaihu-shugan-san
keywords: Active constituents; Bai-Shao; Chaihu-Shu-Gan-San; Chemical fingerprinting; Integrated strategy; Urinary metabonomics