Pharmacokinetics, Tissue Distribution and Protein Binding Studies of Chrysocauloflavone I in Rats

Abstract

Chrysocauloflavone I, an unfrequent biflavonoid, was purified from Selaginella doederleinii in this study. It showed cytotoxic effects on three human cancer cells, NCI-H1975, A549, and HepG-2, in vitro. In silico assessment of the physicochemical properties was performed for predicting the permeability and intestinal absorption of the tested compound. Subsequently, a rapid, sensitive, and specific high-performance liquid chromatography method was developed for determination of the compound in different biological samples to ascertain the pharmacokinetics, tissue distribution, and protein binding profiles of this active ingredient in rats. After intravenous dosing of chrysocauloflavone I at different levels (10 and 20 mg/kg), the elimination half-life was approximately 85 min, and the AUC0-∞ increased with the dose from 148.52 mg/L × min for 10 mg/kg to 399.01 mg/L × min for 20 mg/kg. After single intravenous dosing (20 mg/kg), chrysocauloflavone I was detected in all tissues studied with higher levels in the heart, blood, and lungs. The results of equilibrium dialysis indicated a very high protein binding degree (over 97%) for chrysocauloflavone I. After intragastric administration of 100 mg/kg chrysocauloflavone I to rats, no parent drug was detected in the rat plasma. This is the first report of the favorable bioactivities, plasma pharmacokinetics, tissue distribution, and protein binding profiles of the rare biflavone chrysocauloflavone I.

Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects

“…Methanolic stock solutions containing biflavonoid reference compounds with known concentrations (about 20 μg/mL) were prepared and stored in a refrigerator (4 °C) until they were required for use. The extract was prepared according to the protocols in the literature [ 8 , 10 ] with slight modification. Described briefly, the dried whole plants of S. doederleinii were pulverized into powder (20–40 mesh).…”

“…The in vivo anticancer effect of the total biflavonoids extract was evaluated according to previous method with slight modification [ 10 , 11 ]. Described briefly, the mouse xenograft model was established by injection of 2 × 10 6 LLC cells s.c. into the right armpit of six to eight-week old C57BL/6 male mice (18–22 g, obtained from the National Rodent Laboratory Animal Resource, Shanghai, China).…”

“…A few components have been isolated from this plant genus, including flavonoids, lignans, polysaccharides, and so on [ 2 ], some of which have been reported to possess anti-diabetic, anti-inflammation, anti-oxidative, and anti-cancer activities [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Modern pharmacological studies showed that the ethanol extract of S. doederleinii could induce human nasopharyngeal carcinoma cell (CNE) apoptosis [ 5 ] and because of abundant biflavonoids, the ethyl acetate extract had more powerful anti-cancer activities than the ethanol extract for S. doederleinii [ 6 , 7 , 8 , 9 , 10 , 11 ]. Our recent studies demonstrated that the biflavonoids in S. doederleinii were concentrated mostly in the ethyl acetate extract, and the total biflavonoids could reduce the expression of antigen Ki67, decrease tumor microvessel density (MVD), and significantly inhibit the tumor growth, and did not show apparent oral acutetoxicity in healthy mice [ 9 ].…”

Therapeutic Applications of Solid Dispersions for Drugs and New Molecules: In Vitro and In Vivo Activities

“…Selaginella doederleinii Hieron is a widely distributed medicinal herb in southern China that has traditionally been used as a folk medicine for cancer, especially lung cancer. However, its total biflavonoid extract (TBESD) has low water solubility, gastrointestinal permeability and oral absorption that limit its use in therapeutic formulations [ 51 , 52 ].…”

A strategy for integrated pharmacokinetic study of cardiovascular herbal medicines based on chemiluminescence and HPLC-MS/MS assays: a case using Danshen injection

“…The extraction recovery, matrix effect and stability of the phenolic acids DSS, PCAL, RA, SAB and SAA were determined by the above-mentioned QC samples according to previous reports. 11,12 FI-CL assay for integrated PK study Firstly, 400 mg of Danshen freeze-dried powder injection was dissolved and diluted into 200 ng mL À1 in water according to the labeled content, 400 mg total phenolic acids/bottle and quantied with SAA as the standard reference (1, 5, 10, 50, 100, 500 and 1000 ng mL À1 ). The result was expressed as SAA equivalent content with the developed FI-CL method.…”