title: Urinary metabonomics study of the hepatoprotective effects of total alkaloids from Corydalis saxicola Bunting on carbon tetrachloride-induced chronic hepatotoxicity in rats using1H NMR analysis.
abstract: Chronic liver injury has been shown to cause liver fibrosis due to the sustained pathophysiological wound healing response of the liver, and eventually progresses to cirrhosis. The total alkaloids of Corydalis saxicola Bunting (TACS), a collection of important bioactive ingredients derived from the traditional Chinese folk medicine Corydalis saxicola Bunting (CS), have been reported to have protective effects on the liver. However, the underlying molecular mechanisms need further elucidation. In this study, the urinary metabonomics and the biochemical changes in rats with carbon tetrachloride (CCl4)-induced chronic liver injury due to treatment TACS or administration of the positive control drug-bifendate were studied via proton nuclear magnetic resonance (1H NMR) analysis. Partial least squares-discriminate analysis (PLS-DA) suggested that metabolic perturbation caused by CCl4damage was recovered with TACS and bifendate treatment. A total of seven metabolites including 2-oxoglutarate, citrate, dimethylamine, taurine, phenylacetylglycine, creatinine and hippurate were considered as potential biomarkers involved in the development of CCl4-induced chronic liver injury. According to pathway analysis using identified metabolites and correlation network construction, the tricarboxylic acid (TCA) cycle, gut microbiota metabolism and taurine and hypotaurine metabolism were recognized as the most affected metabolic pathways associated with CCl4chronic hepatotoxicity. Notably, the changes in 2-oxoglutarate, citrate, taurine and hippurate during the process of CCl4-induced chronic liver injury were significantly restored by TACS treatment, which suggested that TACS synergistically mediated the regulation of multiple metabolic pathways including the TCA cycle, gut microbiota metabolism and taurine and hypotaurine metabolism. This study could bring valuable insight to evaluating the efficacy of TACS intervention therapy, help deepen the understanding of the hepatoprotective mechanisms of TACS and enable optimal diagnosis of chronic liver injury.
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning 530021, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
authors.affiliation: The First Affiliated Hospital, Guangxi Traditional Chinese Medicine University, Nanning 530023, China.
authors.forename: Zheng-Teng
authors.initials: ZT
authors.lastname: Yang
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
authors.forename: Bang
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Wu
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
authors.forename: Xu-Wen
authors.initials: XW
authors.lastname: Liu
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
authors.forename: Chao-Ling
authors.initials: CL
authors.lastname: Tang
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
authors.forename: Shi-Yin
authors.initials: SY
authors.lastname: Lu
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
authors.forename: Zhao-Ni
authors.initials: ZN
authors.lastname: Chen
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Song
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
authors.forename: Jun-Xiang
authors.initials: JX
authors.lastname: Ruan
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China; Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Hong-Ye
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Liang
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China. Electronic address: gxsonghui@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Song
authors.affiliation: Pharmaceutical College, Guangxi Medical University, Nanning 530021, China. Electronic address: suzhiheng915@126.com.
authors.forename: Zhi-Heng
authors.initials: ZH
authors.lastname: Su
mesh_terms: D000470:Alkaloids; D000818:Animals; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury; D031311:Corydalis; D008099:Liver; D055432:Metabolomics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000470:Alkaloids; D002251:Carbon Tetrachloride
keywords: (1)H NMR; Carbon tetrachloride; Chronic liver injury; Metabonomics; Total alkaloids of Corydalis saxicola bunting