Identification of a rare sulfonic acid metabolite of andrographolide in rats
Identification of a rare sulfonic acid metabolite of andrographolide in rats
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DOI：
10.1124/dmd.31.8.983
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发表时间：
2003-08-01
影响因子：
3.9
通讯作者：
Yao, XS
中科院分区：
文献类型：
--
作者：
He, XG;Li, JK;Yao, XS
穿心莲内酯作为抗炎和抗生素药物广泛应用于临床。本文研究了大鼠单次口服120 mg/kg穿心莲内酯后的代谢物。通过与合成标准品进行比较，通过高分辨率质谱、NMR 光谱（包括 H-1 NMR、C-13 NMR 和二维 NMR）阐明了代谢物的结构。穿心莲内酯在大鼠体内的主要代谢物是14-脱氧-12(R)-磺基穿心莲内酯。在所提出的机制中，α，β-不饱和羰基的β-碳被磺酸攻击，形成磺酸盐化合物。这是一种罕见的代谢反应。它可能是穿心莲内酯在大鼠体内的主要代谢途径。磺酸盐代谢物的极性大大增加，很容易从体内排出。
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 H-1 NMR, C-13 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.