Qiu Feng, Cui Liang, Chen Lixia, Sun Jiawen, Yao Xinsheng
Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
Xenobiotica. 2012 Sep;42(9):911-6. doi: 10.3109/00498254.2012.680619. Epub 2012 May 9.
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.
穿心莲内酯是传统中药和印度草药中的一种主要半日花烷二萜类化合物。穿心莲（爵床科）在中国临床上主要用于治疗发热、感冒和炎症。在我们之前的研究中，在人尿液中鉴定出了15种穿心莲内酯代谢物。然而，仍有另外两种未知代谢物。本研究的目的是阐明这两种代谢物的结构。3. 这两种可能为差向异构体的代谢物被鉴定为肌酐加合物，通过光谱证据确定它们的结构分别为14-脱氧-12-（肌酐-5-基）-穿心莲内酯-19-O-β-D-葡萄糖醛酸苷A（代谢物1）和14-脱氧-12-（肌酐-5-基）-穿心莲内酯-19-O-β-D-葡萄糖醛酸苷B（代谢物2）。4. 首次报道了肌酐加合物作为一种新的代谢途径的形成。推测其机制为，α,β-不饱和羰基的β-碳（C-12）受到通过消除一个质子形成的肌酐5-阴离子中间体的攻击，随后双键从12(13)迁移至13(14)，并消除C-14处的羟基。
