Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
Planta Med. 2010 Nov;76(16):1859-63. doi: 10.1055/s-0030-1250053. Epub 2010 Jun 14.
Coptidis Rhizoma has been used as a traditional Chinese herbal medicine to treat typhoid, pharyngolaryngitis, diabetes mellitus, gastroenteritis and secretory diarrhea for more than a thousand years in China. However, there is little information on the IN VIVO chemical constituents of Coptidis Rhizoma following oral administration. In this paper, the alkaloid constituents in urine were studied in humans following oral administration of Coptidis Rhizoma decoction. Using macroporous adsorption resin chromatography, open ODS column chromatography, and preparative high-performance liquid chromatography, twelve protoberberine alkaloid constituents were isolated. Their structures were elucidated by chemical evidence, enzymatic deconjugation and analyses of mass, (1)H-NMR and NOESY spectra. The identified alkaloid constituents include berberine ( P1), groenlandicine 3-O- β-D-glucuronide (M1), dehydrocheilanthifoline 2-O-β-D-glucuronide (M2), thalifendine 10-O-β-D-glucuronide (M3), jatrorrhizine 3-O-β-D-glucuronide (M4), columbamine 2-O-β-D-glucuronide (M5), berberrubine 9-O-β-D-glucuronide (M6), jatrorrhizine 3-O-sulfate (M7), demethyleneberberine 2-O-sulfate (M8), dehydrocorydalmine 10-O-sulfate (M9), 3,10-demethylpalmatine 10-O-sulfate (M10) and 2,3,10-trihydroxyberberine 2-O-sulfate ( M11). No other parent protoberberine alkaloids from Coptidis Rhizoma except for a trace of berberine were found in the urine. These findings suggested that the protoberberine alkaloids, which were absorbed in vivo following oral administration of Coptidis Rhizoma decoction, were mainly conjugated with glucuronic acid or sulfuric acid to form phase II metabolites directly or after biotransformation to phase I metabolites, and finally excreted in urine.
黄连作为一种传统中药，在中国已有一千多年的历史，用于治疗伤寒、咽喉炎、糖尿病、肠胃炎和分泌性腹泻。然而，关于口服黄连后体内的化学成分知之甚少。本文研究了口服黄连汤后尿液中的生物碱成分。采用大孔吸附树脂色谱、开放 ODS 柱色谱和制备高效液相色谱法，从黄连中分离得到 12 种原小檗碱类生物碱成分。根据化学证据、酶解和质谱、(1)H-NMR 和 NOESY 图谱分析，确定了它们的结构。鉴定出的生物碱成分包括小檗碱（P1）、小檗红碱 3-O-β-D-葡萄糖醛酸苷（M1）、脱氢千金藤啶碱 2-O-β-D-葡萄糖醛酸苷（M2）、唐松草定 10-O-β-D-葡萄糖醛酸苷（M3）、延胡索乙素 3-O-β-D-葡萄糖醛酸苷（M4）、小檗碱 2-O-β-D-葡萄糖醛酸苷（M5）、黄连碱 9-O-β-D-葡萄糖醛酸苷（M6）、延胡索乙素 3-O-硫酸盐（M7）、二氢小檗碱 2-O-硫酸盐（M8）、脱氢刻叶紫堇灵 10-O-硫酸盐（M9）、3,10-二甲基黄连碱 10-O-硫酸盐（M10）和 2,3,10-三羟基小檗碱 2-O-硫酸盐（M11）。在尿液中除了微量的小檗碱外，没有发现黄连中原小檗碱类的其他母体生物碱。这些发现表明，口服黄连汤后，体内吸收的原小檗碱类生物碱主要与葡萄糖醛酸或硫酸结合，直接或经生物转化为 I 相代谢物后形成 II 相代谢物，最终从尿液中排出。
