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Planta Med 2016; 82(03): 217-223
DOI: 10.1055/s-0035-1558159
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

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

Sufang Yang   *
1   College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
,
Peiying Shi   *
2   Department of TCM Resource and Apitherapy, Bee Science College, Fujian Agriculture and Forestry University, Fuzhou, China
,
Xiaomei Huang
3   Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China
,
Meifeng Zhao
3   Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China
,
Shaoguang Li
3   Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China
,
Youjia Wu
3   Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China
,
Xinhua Lin
3   Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China
,
Hong Yao
3   Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, China
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Publikationsverlauf

received 10. Februar 2015
revised 16. September 2015

accepted 19. September 2015

Publikationsdatum:
17. November 2015 (online)

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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.

Key words

Selaginella doederleinii - Selaginellaceae - chrysocauloflavone I - cytotoxicity - pharmacokinetics - plasma protein binding - distribution

* These authors contributed equally to this work.


Supporting Information

 

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