ABSTRACT
BACKGROUND AND OBJECTIVES: Licorice is the dried roots and rhizomes of Glycyrrhiza uralensis Fisch (Leguminosae), which is often used with paclitaxel to alleviate paclitaxel-induced pain in clinics. However, the herb-drug interaction between licorice and paclitaxel is still unknown. Our study evaluates the effects of oral licorice on the paclitaxel in rats via pharmacokinetic studies. METHODS: A simple and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine paclitaxel in rat. SD rats were randomly divided into 3 groups of 6 animals each as follows: two groups of rats that were pretreated with a daily gavage of licorice (3 g/kg) for 1 or 14 successive days; Control group that was administered distilled water. All rats were then intravenously administered with paclitaxel (3 mg/kg). RESULTS: The results showed that 14 days pretreatment of licorice could decrease the area under the curve (AUC0-t) (from 7483.08 ± 528.78 to 6679.12 ± 266.56 mg/L × h) (P < 0.01), and increase the total clearance (CL) (from 0.36 ± 0.02 to 0.39 ± 0.02 L/h/kg) of paclitaxel (P < 0.01). However, a single co-administration of licorice did not significantly alter the pharmacokinetic parameters of paclitaxel, such as AUC0-t (from 7483.08 ± 528.78 to 7201.24 ± 292.76 mg/L × h) (P > 0.05) and CL (from 0.36 ± 0.02 to 0.36 ± 0.01 L/h/kg) (P > 0.05). CONCLUSIONS: The results will contribute to better use of licorice in the adjunctive therapy and provide information to study the interaction between herbs and chemotherapy.
Subject(s)
Glycyrrhiza/chemistry , Herb-Drug Interactions , Paclitaxel/pharmacokinetics , Plant Extracts/pharmacology , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/analysis , Antineoplastic Agents, Phytogenic/pharmacokinetics , Area Under Curve , Chromatography, High Pressure Liquid , Male , Paclitaxel/administration & dosage , Paclitaxel/analysis , Plant Extracts/administration & dosage , Rats , Rats, Sprague-Dawley , Tandem Mass SpectrometryABSTRACT
OBJECTIVE: To express and purify FOXO1 DNA binding domain (DBD) and to evaluate its DNA binding properties.â© Methods: Gene sequence of FOXO1-DBD was optimized and the recombinant strains were induced at low temperature to obtain soluble protein of FOXO1-DBD. Then, FOXO1-DBD protein was purified through Ni affinity chromatography and cation exchange. Finally, the DNA binding properties of FOXO1-DBD was evaluated by electrophoretic mobility shift assay (EMSA).â© Results: Most of soluble proteins were obtained by optimizing its genes sequence and induction at 21 â. Over 95% purity of FOXO1-DBD protein was obtained through two-steps purification. Purified protein exhibited good binding property to the DNA binding motif (G/ATAAACA) of FOX family.â© Conclusion: An efficient expression and purification method for FOXO1-DBD is established, and the complexity of FOXO1 protein in recognition of DNA is verified.