Wang Hai-Qiao,Gong Xiao-Mei,Lan Fen,Zhang Yi-Han,Xia Jin-Er,Zhang Hai,Guo Jia-Lin,Liu Min
Background: Timosaponin A-III is one of the most promising active saponins from Anemarrhena asphodeloides Bge. As an oral chemotherapeutic agent, there is an urgent need to clarify its biopharmaceutics and pharmacokinetics to improve its development potential. Objective: This research
explores the bioavailability of timosaponin A-III and clarifies its absorption and metabolism mechanisms by a sensitive and specific HPLC-MS/MS method. Methods: Pharmacokinetics and bioavailability studies of timosaponin A-III were performed in Sprague- Dawley rats by oral (20 mg/kg)
and intravenous administration (2 mg/kg). Control group was given the same volume of normal saline. The absorption of timosaponin A-III was investigated in a rat intestinal perfusion model in situ and a Caco-2 cell transport model in vitro. The metabolic rate of timosaponin A-III was determined
in a rat liver microsome incubation system. Results: After the oral administration, timosaponin A-III reached Cmax of 120.90 ± 24.97 ng/mL at 8 h, and the t1/2 was 9.94 h. The absolute oral bioavailability of timosaponin A-III was 9.18%.
The permeability coefficients of timosaponin A-III in four intestinal segments ranged from 4.98 to 5.42 10-7 cm/s, indicating a difficult absorption. A strikingly high efflux transport of timosaponin A-III was found, PappBA 3.27 ± 0.64 10−6
cm/s, which was abolished by a P-gp inhibitor. Rat liver microsome incubation studies showed that timosaponin A-III could hardly be metabolized, with a t1/2 of over 12 h. In addition, the solubility test showed a low solubility in PBS solution, i.e. 30.58 μg/mL.
Conclusion: Timosaponin A-III exhibited low oral bioavailability by oral and intravenous administration, which was probably caused by its low permeability and solubility. This study may provide a reference for its rational clinical use and further study on the pharmacology or toxicology of
timosaponin A-III.
Wenying Zhou,Xue Han,Yanjun Wu,Guochao Shi,Shiqi Xu,Mingli Wang,Wenzhi Yuan,Jiahao Cui,Zelong Li
An effective SERS-based detection method assisted by machine learning algorithm has been developed to intelligently identify the pharmacodynamic substances in traditional Chinese medicine (TCM) which aided in the quality control and identification of TCM. In this work, the ultrasensitive grating-like core-shell Ag@SiO2@Cu@moth wing (Ag@SiO2@Cu@MW) SERS platform was explored which can precisely control the intergap distances by adjusting the thickness of the SiO2 layer. This SERS platform demonstrated reproducibility and reliability, with a low relative standard deviation (RSD) of 7.38% and an enhancement factor (EF) of 2.49 × 107. The optimized Ag30@SiO2(4)@Cu20@MW substrate were then applied in the accurately analyzing pharmacodynamic substances. Specifically, the label-free SERS analysis showed the distinct spectral features for Jujuboside A, Saikosaponin A and Timosaponin A-III. Machine learning algorithms, such as principal component analysis (PCA), decision tree (DT), support vector machine (SVM), k-nearest neighbors (kNN) were employed and further in differentiating with the three pharmacodynamic substances Raman spectrum groups. These results indicate that SERS technology in combination with machine learning algorithms can not only achieve rapid and accurate detection of different types of pharmacodynamic substances, but also promote the modernization and international application of TCM.
危险品化学品经营许可证（带存储）