Feng Nian-Ping, Di Bin, Liu Wen-Ying
Department of Pharmaceutics, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 PR China.
Chem Pharm Bull (Tokyo). 2005 Aug;53(8):978-83. doi: 10.1248/cpb.53.978.
Shuang-Huang-Lian (SHL) is a traditional Chinese formula containing Flos lonicerae, Radix scutellariae (RS) and Fructus forsythiae, and is commonly used for treating acute upper respiratory tract infection, acute bronchitis and light pneumonia. The aim of the present study is to compare the metabolites of baicalin in rats when orally administered with SHL and Radix scutellariae, and try to explore the principle of SHL compatibility. By using LC-MS(n) and HPLC-DAD, the metabolites of baicalin were analyzed from bile, urine and feces of rats dosed with SHL and RS. Our results showed significant difference of baicalin metabolism between RS and SHL. However, baicalein was found to be the main metabolites of baicalin in intestinal tract after oral administration of RS and SHL, glucuronide, glucoside and methylated products were also found in rat urine after administration of either RS or SHL. Meanwhile, several sulphates were found in rat urine after RS administration, but not found after SHL. Among the metabolites of the SHL, potentially there existed a isomerized baicalin and methylated product: 5,7-dihydroxy-6-methoxyisoflavone-7-O-beta-glucopyranuronoside, but without unidentified metabolite M3. Baicalein-6-O-beta-glucopyranuronoside-7-O-beta-glucopyranuronoside and baicalein-6-O-beta-glucose-7-O-beta-glucopyranuronoside were first reported by this study. The major metabolites of baicalin of RS and SHL in rat bile were the same, including baicalin-6-O-beta-glucopyranuronoside-7-O-beta-glucopyranuronoside, baicalin-6-beta-glucopyranuronoside and 6-O-methyl-baicalin-7-O-beta-glucopyranuronoside. Moreover, baicalein-6-O-beta-glucose-7-O-beta-glucopyranuronoside was also first found in rat bile by this study. Although baicalin-6-O-sulfate-7-O-beta-glucopyranuronoside was found in rat bile after RS administration, no sulphated products were found after oral administration of SHL. These differences of baicalin metabolism between RS and SHL indicated that compatibility of medicines could result in the differences of metabolites.
双黄连（SHL）是一种包含金银花、黄芩（RS）和连翘的传统中药配方，常用于治疗急性上呼吸道感染、急性支气管炎和轻度肺炎。本研究的目的是比较大鼠口服双黄连和黄芩后黄芩苷的代谢产物，并试图探索双黄连配伍的原理。通过使用液相色谱-质谱联用仪（LC-MS(n)）和高效液相色谱-二极管阵列检测器（HPLC-DAD），分析了给予双黄连和黄芩的大鼠胆汁、尿液和粪便中黄芩苷的代谢产物。我们的结果表明，黄芩和双黄连之间黄芩苷代谢存在显著差异。然而，口服黄芩和双黄连后，黄芩素被发现是肠道中黄芩苷的主要代谢产物，给予黄芩或双黄连后大鼠尿液中也发现了葡萄糖醛酸苷、糖苷和甲基化产物。同时，给予黄芩后大鼠尿液中发现了几种硫酸盐，但给予双黄连后未发现。在双黄连的代谢产物中，可能存在一种异构化黄芩苷和甲基化产物：5,7-二羟基-6-甲氧基异黄酮-7-O-β-葡萄糖醛酸苷，但没有未鉴定的代谢产物M3。黄芩素-6-O-β-葡萄糖醛酸苷-7-O-β-葡萄糖醛酸苷和黄芩素-6-O-β-葡萄糖-7-O-β-葡萄糖醛酸苷首次由本研究报道。黄芩和双黄连在大鼠胆汁中黄芩苷的主要代谢产物相同，包括黄芩素-6-O-β-葡萄糖醛酸苷-7-O-β-葡萄糖醛酸苷、黄芩苷-6-β-葡萄糖醛酸苷和6-O-甲基黄芩苷-7-O-β-葡萄糖醛酸苷。此外，本研究还首次在大鼠胆汁中发现了黄芩素-6-O-β-葡萄糖-7-O-β-葡萄糖醛酸苷。虽然给予黄芩后大鼠胆汁中发现了黄芩苷-6-O-硫酸盐-7-O-β-葡萄糖醛酸苷，但口服双黄连后未发现硫酸化产物。黄芩和双黄连之间黄芩苷代谢的这些差异表明药物配伍可能导致代谢产物的差异。
