title: 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.
authors.affiliation: College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of TCM Resource and Apitherapy, Bee Science College, Fujian Agriculture and Forestry University, Fuzhou, China.
authors.forename: Peiying
authors.initials: P
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China.
authors.forename: Meifeng
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China.
authors.forename: Shaoguang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China.
authors.forename: Youjia
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D044946:Biflavonoids / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007408:Intestinal Absorption; D010936:Plant Extracts / Q000493:pharmacokinetics*; D010946:Plants, Medicinal / Q000737:chemistry*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D032503:Selaginellaceae / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044946:Biflavonoids; D010936:Plant Extracts; C000611561:chrysocauloflavone I