Identification of a rare sulfonic acid metabolite of andrographolide in rats.
Andrographolide is widely used in clinic as an anti-inflammatory and antibiotic drug. In this paper, the metabolites of andrographolide in rats after single oral doses of 120 mg/kg were investigated. The structures of the metabolites were elucidated by high-resolution mass spectra, NMR spectroscopy including 1H NMR, 13C NMR, and two-dimensional NMR, through comparison to a synthetic standard. The main metabolite of andrographolide in rats was 14-deoxy-12(R)-sulfo andrographolide. In the proposed mechanism, the beta-carbon of alpha, beta-unsaturated carbonyl was attacked by sulfonic acid, to form the sulfonate compound. This was a rare metabolic reaction. It may be the main metabolic pathway of andrographolide in rats. The polarity of the sulfonate metabolite increased greatly and could be easily eliminated from body.
He
Xiangjiu
X
Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang, China, 110016.
Li
Jiankuan
J
Gao
Hao
H
Qiu
Feng
F
Hu
Ke
K
Cui
Xiangmin
X
Yao
Xinsheng
X
D000284:Administration, Oral; D000818:Animals; D002247:Carbon Isotopes; D004224:Diterpenes / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D007421:Intestine, Small / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D015394:Molecular Structure; D051381:Rats / Q000378:metabolism*; D017208:Rats, Wistar; D013451:Sulfonic Acids / Q000737:chemistry* / Q000302:isolation & purification* / Q000652:urine
C487001:14-deoxy-12-sulfoandrographolide; D002247:Carbon Isotopes; D004224:Diterpenes; D013451:Sulfonic Acids; C030419:andrographolide