Shi Xuqin, Tang Yuping, Zhu Huaxu, Li Weixia, Li Wei, Li Zhenhao, Luo Niancui, Duan Jin-ao
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engeering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engeering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
J Ethnopharmacol. 2014 Apr 11;153(1):169-77. doi: 10.1016/j.jep.2014.02.004. Epub 2014 Feb 26.
Blood deficiency is commonly encountered among women, and is the root of many gynecological disorders. Danggui Buxue Decoction (DBD), a classical traditional Chinese formula which is composed of Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) at the ratio of 5:1 (w/w), is widely used in TCM clinics for treatment of blood deficiency syndrome. This study is to compare the in vivo pharmacokinetic properties of seven major bio-active components in normal and blood deficiency rats after oral administration of DBD.
Blood deficiency rats were induced by bleeding from orbit at the dosages of 5.0mL/kg each day for 12 days. Normal and blood deficiency rats were administrated of DBD on the 12th day at the dosage of 20g/kg, and blood was collected at different time points after then. Concentrations of ferulic acid, caffeic acid, butylphthalide, ligustilide, calycosin-7-O-β-glucoside, ononin, and astragaloside IV in plasma were quantified by UPLC-TQ/MS, and the main pharmacokinetic parameters were calculated by DAS 2.0.
It was found that Cmax, Tmax and MRT0T of astragaloside IV, Cmax, T1/2Z, AUC0T and MRT0T of calycosin-7-O-β-glucoside, T1/2Z and AUC0T of ferulic acid, T1/2Z, AUC0T and MRT0T of ononin, and MRT0~T of ligustilide, butylphthalide, and caffeic acid in blood deficiency rats was significantly different (P<0.05) from normal rats.
This study was the first report about pharmacokinetic investigation in blood deficiency animals which was conducted by bleeding. And the results demonstrated that the seven DBD constituents in normal and blood deficiency rats had obvious differences in some pharmacokinetic characteristics, suggesting that the rate and extent of drug metabolism were altered in blood deficiency animals.
血虚在女性中较为常见,是许多妇科疾病的根源。当归补血汤(DBD)是一种经典的中药方剂,由黄芪(AR)和当归(ASR)按5:1(w/w)的比例组成,在中医临床中广泛用于治疗血虚证。本研究旨在比较正常大鼠和血虚大鼠口服DBD后七种主要生物活性成分的体内药代动力学特性。
通过每天眼眶放血5.0mL/kg,连续放血12天诱导血虚大鼠。在第12天,正常大鼠和血虚大鼠按20g/kg的剂量给予DBD,随后在不同时间点采集血液。采用超高效液相色谱-串联质谱法(UPLC-TQ/MS)测定血浆中阿魏酸、咖啡酸、丁基苯酞、藁本内酯、毛蕊异黄酮-7-O-β-葡萄糖苷、芒柄花苷和黄芪甲苷的浓度,并使用DAS 2.0计算主要药代动力学参数。
发现血虚大鼠中黄芪甲苷的Cmax、Tmax和MRT0T,毛蕊异黄酮-7-O-β-葡萄糖苷的Cmax、T1/2Z、AUC0T和MRT0T,阿魏酸的T1/2Z和AUC0T,芒柄花苷的T1/2Z、AUC0T和MRT0T,以及藁本内酯、丁基苯酞和咖啡酸的MRT0~T与正常大鼠相比有显著差异(P<0.05)。
本研究是首次关于通过放血诱导血虚动物进行药代动力学研究的报道。结果表明,正常大鼠和血虚大鼠中DBD的七种成分在某些药代动力学特征上存在明显差异,提示血虚动物的药物代谢速率和程度发生了改变。