Zhang Wei, Li Nian-Guang, Tang Yu-Ping, Dong Ze-Xi, Gu Ting, Wu Wen-Yu, Zhang Peng-Xuan, Yu Shao-Peng, Duan Jin-Ao, Shi Zhi-Hao
a Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine , Nanjing University of Chinese Medicine , Nanjing , P.R. China ;
b Department of Organic Chemistry , China Pharmaceutical University , Nanjing , P.R. China.
Pharm Biol. 2016 Oct;54(10):2158-67. doi: 10.3109/13880209.2016.1149495. Epub 2016 Mar 9.
Context Scutellarin (1) has been widely used in China to treat acute cerebral infarction and paralysis induced by cerebrovascular diseases. However, scutellarin (1) has unstable metabolic characteristics. Objective The metabolic profile of 6-O-scutellarein was studied to determine its metabolic stability in vivo. Materials and methods In this study, a method of UFLC/Q-TOF MS was used to study the 6-O-methyl-scutellarein metabolites in rat plasma, urine, bile and faeces after oral administration of 6-O-methyl-scutellarein (3). One hour after oral administration of 6-O-methyl-scutellarein (3) (34 mg/kg), approximately 1 mL blood samples were collected in EP tubes from all groups. Bile, urine and faeces samples were collected from eight SD rats during 0-24 h after oral administration. The mass defect filtering, dynamic background subtraction and information dependent acquisition techniques were also used to identify the 6-O-methyl-scutellarein metabolites. Results The parent compound 6-O-methyl-scutellarein (3) was found in rat urine, plasma, bile and faeces. The glucuronide conjugate of 6-O-methyl-scutellarein (M1, M2), diglucuronide conjugate of 6-O-methyl-scutellarein (M3), sulphate conjugate of 6-O-methyl-scutellarein (M4), glucuronide and sulphate conjugate of 6-O-methyl-scutellarein (M5), methylated conjugate of 6-O-methyl-scutellarein (M6) were detected in rat urine. M1, M2 and M3 were detected in rat bile. M1 was found in rat plasma and M7 was detected in faeces. Discussion and conclusion Because the parent compound 6-O-methyl-scutellarein (3) was found in rat urine, plasma, bile and faeces, we speculate that 6-O-methyl-scutellarein (3) had good metabolic stability in vivo. This warrants further study to develop it as a promising candidate for the treatment of ischemic cerebrovascular disease.
背景 灯盏花素（1）在中国已被广泛用于治疗急性脑梗死和脑血管疾病引起的瘫痪。然而，灯盏花素（1）具有不稳定的代谢特性。目的 研究6-O-灯盏花乙素的代谢谱，以确定其在体内的代谢稳定性。材料与方法 在本研究中，采用超高效液相色谱/四极杆飞行时间质谱联用（UFLC/Q-TOF MS）方法，研究大鼠口服6-O-甲基灯盏花乙素（3）后血浆、尿液胆汁和粪便中的6-O-甲基灯盏花乙素代谢产物。口服6-O-甲基灯盏花乙素（3）（34 mg/kg）1小时后，从所有组的大鼠中收集约1 mL血样于EP管中。在口服给药后的0至24小时内，从8只SD大鼠收集胆汁、尿液和粪便样本。还采用质量亏损过滤、动态背景扣除和信息依赖采集技术鉴定6-O-甲基灯盏花乙素代谢产物。结果 在大鼠尿液、血浆、胆汁和粪便中均发现母体化合物6-O-甲基灯盏花乙素（3）。在大鼠尿液中检测到6-O-甲基灯盏花乙素的葡萄糖醛酸结合物（M1、M2）、6-O-甲基灯盏花乙素的二葡萄糖醛酸结合物（M3）、6-O-甲基灯盏花乙素的硫酸结合物（M4）、6-O-甲基灯盏花乙素的葡萄糖醛酸和硫酸结合物（M5）、6-O-甲基灯盏花乙素的甲基化结合物（M6）。在大鼠胆汁中检测到M1、M2和M3。在大鼠血浆中发现M1，在粪便中检测到M7。讨论与结论 由于在大鼠尿液、血浆、胆汁和粪便中均发现母体化合物6-O-甲基灯盏花乙素（3），我们推测6-O-甲基灯盏花乙素（3）在体内具有良好的代谢稳定性。这值得进一步研究，以将其开发成为治疗缺血性脑血管疾病的有前景的候选药物。
