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目的从中药葛根中提取脑内苯并二氮杂卓(BZ)受体活性化合物。方法用体外的放射配体-受体结合法(RRA)和高压液相法(HPLC)提取、分离、纯化BZ受体活性化合物,用核磁共振和质谱仪确定活性化合物的结构。后用GABA比和Scatchardplot分析确定它们的作用特性。结果从葛根中提取、分离到葛根素和大豆甙元2种活性化合物。它们在体外可抑制3H-氟硝西泮和脑细胞膜的结合,IC50值分别为(18.46±2.34)μmol/L和(15.4±31.89)μmol/L。大豆甙元还可抑制3H-呱唑嗪和α1-肾上腺素受体的结合(IC50值为89μmol/L)。2种化合物的GABA比分别为1.11和1.12,提示2种黄酮化合物是BZ受体的拮抗剂或部分激动剂。Scatchardplot分析显示2种化合物对3H-氟硝西泮和脑膜结合的抑制是通过竞争性与非竞争性混合机制而实现的。结论葛根素和大豆甙元是脑内BZ受体的拮抗剂或部分激动剂。它们的抑制作用是通过竞争性与非竞争性混合机制而实现的。
Objective To extract the active compounds of benzodiazepine (BZ) receptors from the pueraria root of traditional Chinese medicine. Methods BZ receptor-reactive compounds were isolated, isolated and purified by in vitro radioligand-receptor binding (RRA) and high pressure liquid chromatography (HPLC). The structures of the active compounds were determined by nuclear magnetic resonance and mass spectrometry. They were then characterized by their GABA ratio and Scatchardplot analysis. Results Two active compounds of puerarin and soybean aglycon were extracted and separated from Radix Puerariae. They inhibited the binding of 3H-flunitrazepam and brain cell membrane in vitro, with IC50 values of (18.46±2.34) μmol/L and (15.4±31.89) μmol/L, respectively. Soybean amaranth also inhibited the binding of 3H-carbazine and α1-adrenergic receptors (IC50 value of 89 μmol/L). The GABA ratios of the two compounds were 1.11 and 1.12, respectively, suggesting that the two flavonoid compounds are antagonists or partial agonists of the BZ receptor. Scatchardplot analysis showed that the inhibition of 3H-flunitrazepam and meningeal binding by both compounds was achieved through a competitive and non-competitive mixing mechanism. Conclusion Puerarin and soy aglycon are antagonists or partial agonists of BZ receptor in brain. Their inhibition is achieved through a mixture of competitive and non-competitive mechanisms.