ABSTRACT
CAT3 is a promising anti-brain tumor agent that has significant anti-tumor activity on Daoy or U87MG orthotopic xenograft in nude mice. This study was carried out to investigate the metabolic profiles of CAT3 in mouse/dog/human blood and microsome as well as in humanized recombinant enzymes. All animal care and experimental procedures were reviewed and approved by the Animal Ethics Committee of Chinese Academy of Medical Sciences. Our findings showed that CAT3 could be hydrolyzed to active metabolite PF403 by carboxylesterase, butyrylcholinesterase and serine hydrolase in mouse/dog/ human blood. PF403 could be further metabolized to M1 oxidative dehydration product, M2 double oxidation dehydration product, M3 methylation oxidative dehydration product, M4 oxidation product and M5 demethylation product, which were mainly catalyzed by CYP1A2, 1A1, 2C9 and 3A4, and slightly by CYP2B6, 2C8, 2C19 and 2D6. Besides oxidative metabolism, PF403 also was transformed into glucuronylation metabolites GLU-PF403 by Phase II enzymes UGT1A1, 1A3 and 1A9. Taken together, the metabolism of CAT3 was a multiple enzyme catalytic reaction. These results could provide valuable information for potential enzyme-mediated DDI in clinic studies.
ABSTRACT
Objective: To design and evaluate Tiandi Zhenchan Instant Powder (TZIP) by promoting the new concept of “taking drugs without water”. Methods: The self-designed formula was used to prepare TZIP. Compared with self-made fine powder, TZIP was evaluated by using taste evaluation, powder properties and solubility evaluation as indicators. Results: The powder had the properties of good taste, short oral retention time and good powder properties. Conclusion: Instant powder is an excellent new dosage form. In this paper, TZIP is taken as an example to provide a new dosage form and evaluation reference for promoting the new concept of “taking drugs without water”.
ABSTRACT
Nobiletin is a kind of polymethoxyflavonoid with many pharmacological effects, such as antiinflammatory and antioxidation activities. This study was carried out to investigate the inhibitory effects of nobiletin on P-glycoprotein (P-gp) in vitro and in vivo. The molecular mechanism for structure-inhibition relationships of nobiletin with P-gp was investigated. Nobiletin exhibited significant inhibition (IC50=2.21 μmol·L-1) on P-gp in MDR1-MDCKⅡ cells. In the cell toxicity test, the paraquat-treated cell viability was decreased with nobiletin by inhibiting P-gp activity. In the rats PK study, the AUC0-t of digoxin was increased 2.02 folds while the Cmax of digoxin was increased 3.29 folds, when nobiletin was used in the pretreatment of SD rats. Molecular docking analysis elucidated that the formation of Pi-Pi bonds with Phe974 was the key factor for P-gp inhibition. The research findings provide important guideline for prediction of potential interaction between nobiletin and P-gp.
ABSTRACT
Taste design and taste masking evaluation is an important part of Chinese materia medica (CMM) preparations design. From the traditional volunteers’ evaluation, animal preference experiments to chemical composition quantitative analysis and electronic tongue intelligent taste evaluation, the sensitivity and resolution of the analysis method are getting higher and higher, however, the correlation with the real feeling of the human body is getting lower and lower. How to satisfy the objective authenticity, high sensitivity, and real-time dynamic quantification of the detection method is an important direction in the development of taste masking technology of CMM preparations. In recent years, functional magnetic resonance imaging (fMRI) technology has been widely used in the clinical diagnosis, acupuncture effect study, and food industry, etc. The basic conditions of fMRI used to taste masking evaluation of CMM preparation tend to mature. In this paper, the basic principle, experimental design and data processing methods of fMRI were introduced, and the influence factors of the experiment were analyzed from the human body and the samples. On this basis, the author puts forward the standard substance concentration-the sensory level of volunteers-brain signal intensity correlation research ideas. It will provide new methods for product optimization and taste improvement of CMM preparations, and also promote the quality evaluation of CMM preparations from experience to scientific evidence.