title: Two novel creatinine adducts of andrographolide in human urine.
abstract: Andrographolide is a major labdane diterpenoid of the traditional Chinese and Ayurvedic medicine. Andrographis paniculate (Burm) Nees, is used in clinical situations in China mainly to treat fever, cold, and inflammation. In our previous study, fifteen metabolites of andrographolide were identified in human urine. However, there are still two other unknown metabolites. The aim of this study was to elucidate the structures of these two metabolites. 3. The two metabolites which are probably epimers were identified as creatinine adducts, and their structures were determined to be 14-deoxy-12-(creatinine-5-yl)-andrographolide-19-O-β-D-glucuronide A (Metabolite 1) and 14-deoxy-12-(creatinine-5-yl)-andrographolide-19-O-β-D-glucuronide B (Metabolite 2) by means of spectroscopic evidences. 4. It is for the first time that the formation of creatinine adducts as a novel metabolic pathway is reported. The mechanism was presumed that β-carbon (C-12) of α, β-unsaturated carbonyl was attacked by a 5-anion intermediate of creatinine formed through elimination of a proton, followed by the double bond migration from 12(13) to 13(14) and elimination of the hydroxyl group at C-14.
authors.affiliation: Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang, People's Republic of China. fengqiu20070118@163.com
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.forename: Liang
authors.initials: L
authors.lastname: Cui
authors.forename: Lixia
authors.initials: L
authors.lastname: Chen
authors.forename: Jiawen
authors.initials: J
authors.lastname: Sun
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Yao
mesh_terms: D002855:Chromatography, Thin Layer; D003404:Creatinine / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D004224:Diterpenes / Q000378:metabolism*; D020719:Glucuronides / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D006801:Humans; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D004224:Diterpenes; D020719:Glucuronides; C030419:andrographolide; D003404:Creatinine