Zhu Na, Cheng Li-Yuan, Zhang Xiao-Ying, Zhang Yue, Zhou Kun
Center of Drug Safety Evaluation, Tianjin University of Traditional Chinese Medicine Tianjin 301617, China Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine Tianjin 301617, China.
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine Tianjin 301617, China.
Zhongguo Zhong Yao Za Zhi. 2024 Mar;49(5):1369-1377. doi: 10.19540/j.cnki.cjcmm.20231207.201.
A total of 11 active ingredients including psoralen, isopsoralen, bakuchiol, bavachalcone, bavachinin, corylin, coryfolin, isobavachalcone, neobavaisoflavone, bakuchalcone, and corylifol A from Psoraleae Fructus in the plasma samples of diabetic and normal rats were simultaneously determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated to elucidate the pharmacokinetic profiles of coumarins, flavonoids, and monoterpene phenols in normal and diabetic rats. The rat model of type 2 diabetes mellitus(T2DM) was induced by a high-sugar and high-fat diet combined with injection of 1% streptozotocin every two days. The plasma samples were collected at different time points after the rats were administrated with Psoraleae Fructus. The proteins in the plasma samples were precipitated by ethyl acetate, and the plasma concentrations of the 11 components of Psoraleae Fructus were determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated by DAS 3.0. The results showed that the pharmacokinetic beha-viors of 8 components including psoralen, isopsoralen, bakuchiol, and bavachinin from Psoraleae Fructus in both female and male mo-del rats were significantly different from those in normal rats. Among them, the coumarins including psoralen, isopsoralen, and corylin showed lowered levels in the blood of both female and male model rats. The flavonoids(bavachinin, corylifol A, and bakuchalcone) and the monoterpene phenol bakuchiol showed decreased levels in the female model rats but elevated levels in the male model rats. It is suggested that the dosage of Psoraleae Fructus should be reasonably adjusted for the patients of different genders at the time of clinical administration.
采用超高效液相色谱-串联质谱法（UHPLC-MS/MS）同时测定糖尿病大鼠和正常大鼠血浆样品中补骨脂果实的11种活性成分，包括补骨脂素、异补骨脂素、毛蕊异黄酮、补骨脂查尔酮、补骨脂宁、紫花前胡苷、紫花前胡素、异补骨脂查尔酮、新补骨脂异黄酮、补骨脂查尔酮和补骨脂酚。计算药代动力学参数以阐明正常大鼠和糖尿病大鼠中香豆素、黄酮类化合物和单萜酚的药代动力学特征。通过高糖高脂饮食联合每两天注射1%链脲佐菌素诱导2型糖尿病（T2DM）大鼠模型。大鼠给予补骨脂果实后，在不同时间点采集血浆样品。血浆样品中的蛋白质用乙酸乙酯沉淀，采用UHPLC-MS/MS测定补骨脂果实11种成分的血浆浓度。药代动力学参数由DAS 3.0计算得出。结果表明，补骨脂果实中的补骨脂素、异补骨脂素、毛蕊异黄酮和补骨脂宁等8种成分在雌性和雄性模型大鼠中的药代动力学行为与正常大鼠显著不同。其中，补骨脂素、异补骨脂素和紫花前胡苷等香豆素在雌性和雄性模型大鼠血液中的含量均降低。黄酮类化合物（补骨脂宁、补骨脂酚和补骨脂查尔酮）和单萜酚毛蕊异黄酮在雌性模型大鼠中的含量降低，但在雄性模型大鼠中的含量升高。提示临床给药时应针对不同性别的患者合理调整补骨脂果实的用量。
