title: Dose-response characteristics of Clematis triterpenoid saponins and clematichinenoside AR in rheumatoid arthritis rats by liquid chromatography/mass spectrometry-based serum and urine metabolomics.
abstract: Clematidis Radix et Rhizoma is a traditional Chinese medicine widely used for treating arthritic disease. Clematis triterpenoid saponins (TS) and clematichinenoside AR (C-AR) have been considered to be responsible for its antiarthritic effects. However, the underling mechanism is still unclear because of their low bioavailability. To address of this issue, metabolomics tools were performed to determine metabolic variations associated with rheumatoid arthritis (RA) and responses to Clematis TS, C-AR and positive drug (Triptolide, TP) treatments. This metabolomics investigation of RA was conducted in collagen-induced arthritis (CIA) rats. Liquid chromatography/mass spectrometry and multivariate statistical tools were used to identify the alteration of serum and urine metabolites associated with RA and responses to drug treatment. As a result, 45 potential metabolites associated with RA were identified. After treatment, a total of 24 biomarkers were regulated to normal like levels. Among these, PC(18:0/20:4), 9,11-octadecadienoic acid, arachidonic acid, 1-methyladenosine, valine, hippuric acid and pantothenic acid etc, were reversed in Clematis TS and C-AR groups. Tetrahydrocortisol was regulated to normal levels in Clematis TS and TP groups, while 3,7,12-trihydroxycholan-24-oic acid was regulated in C-AR and TP groups. Biomarkers like citric acid, p-cresol glucuronide, creatinine, cortolone were reversed in TP group.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lin-Xiu
authors.initials: LX
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wen-Qi
authors.initials: WQ
authors.lastname: Chang
authors.affiliation: Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, No. 818 Xingwan Road, Nanchang 330004, Jiangxi Province, China.
authors.forename: Jian-Qun
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, China. Electronic address: liulifang69@126.com.
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xingz@cpu.edu.cn.
authors.forename: Gui-Zhong
authors.initials: GZ
authors.lastname: Xin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002853:Chromatography, Liquid; D039324:Clematis / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005260:Female; D013058:Mass Spectrometry; D055442:Metabolome / Q000187:drug effects*; D017208:Rats, Wistar; D012503:Saponins / Q000302:isolation & purification / Q000627:therapeutic use*; D014315:Triterpenes / Q000302:isolation & purification / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D012503:Saponins; D014315:Triterpenes; C000599570:clematichinenoside AR
keywords: Biomarkers; Clematichinenoside AR; Clematidis Radix et Rhizoma; Clematis triterpenoid saponins; Metabolomics; Rheumatoid arthritis