He Xiangjiu, Li Jiankuan, Gao Hao, Qiu Feng, Hu Ke, Cui Xiangmin, Yao Xinsheng
Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang, China, 110016.
Drug Metab Dispos. 2003 Aug;31(8):983-5. doi: 10.1124/dmd.31.8.983.
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.
穿心莲内酯作为一种抗炎和抗生素药物在临床上被广泛使用。本文研究了大鼠单次口服120 mg/kg穿心莲内酯后的代谢产物。通过与合成标准品比较，利用高分辨率质谱、核磁共振光谱（包括1H NMR、13C NMR和二维NMR）阐明了代谢产物的结构。大鼠体内穿心莲内酯的主要代谢产物是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。磺酸盐代谢产物的极性大大增加，并且可以很容易地从体内消除。
