Download PDF
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
› Author Affiliations
Further Information

Publication History

received 10 February 2015
revised 16 September 2015

accepted 19 September 2015

Publication Date:
17 November 2015 (online)

Also available at
    Permissions and Reprints

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

 

  • References

  • 1 Siegel R, Ma JM, Zou ZH, Jemal A. Cancer statistics. CA Cancer J Clin 2014; 64: 9-29
    CrossrefPubMedSearch in Google Scholar
  • 2 Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 2010; 19: 1893-1907
    CrossrefPubMedSearch in Google Scholar
  • 3 Li SG, Yao H, Zhao MF, Li YX, Huang LY, Lin XH. Determination of seven biflavones of Selaginella doederleinii by high performance liquid chromatography. Anal Lett 2013; 46: 2835-2845
    CrossrefPubMedSearch in Google Scholar
  • 4 Li SG, Zhao MF, Li YX, Sui YX, Yao H, Huang LY, Lin XH. Preparative isolation of six anti-tumour biflavonoids from Selaginella Doederleinii Hieron by high-speed counter-current chromatography. Phytochem Anal 2014; 25: 127-133
    CrossrefPubMedSearch in Google Scholar
  • 5 Liu HH, Peng H, Ji ZH, Zhao SW, Zhang YF, Wu J, Fan JP, Liao JC. Reactive oxygen species-mediated mitochondrial dysfunction is involved in apoptosis in human nasopharyngeal carcinoma CNE cells induced by Selaginella doederleinii extract. J Ethnopharmacol 2011; 138: 184-191
    CrossrefPubMedSearch in Google Scholar
  • 6 Talbi A, Zhao D, Liu QW, Li JX, Fan AL, Yang W, Han X, Chen XJ. Pharmacokinetics, tissue distribution, excretion and plasma protein binding studies of wogonin in rats. Molecules 2014; 19: 5538-5549
    CrossrefPubMedSearch in Google Scholar
  • 7 Lin R, Peyroux J, Seguin E, Koch M. Hypertensive effect of glycosidic derivatives of hordenine isolated from Selaginella doederleinii Hieron and structural analogues in rats. Phytother Res 1991; 5: 188-190
    CrossrefPubMedSearch in Google Scholar
  • 8 Lee CW, Choi HJ, Kim HS, Kim DH, Chang IS, Moon HT, Lee SY, Oh WK, Woo ER. Biflavonoids isolated from Selaginella tamariscina regulate the expression of matrix metalloproteinase in human skin fibroblasts. J Med Chem 2008; 16: 732-738
    PubMedSearch in Google Scholar
  • 9 Lee NY, Min HY, Lee J, Nam JW, Lee YJ, Han AR, Wiryawan A, Suprapto W, Lee SK, Seo EK. Identification of a new cytotoxic biflavanone from Selaginella doederleinii . Chem Pharm Bull 2008; 56: 1360-1361
    CrossrefPubMedSearch in Google Scholar
  • 10 Li S, Zhu RH, Zhong M, Zhang YP, Huang KL, Zhi X, Fu S. Effects of ultrasonic-assistant extraction parameters on total flavones yield of Selaginella doederleinii and its antioxidant activity. J Med Plants Res 2010; 4: 1743-1750
    PubMedSearch in Google Scholar
  • 11 Swamy RC, Kunert O, Schühly W, Bucar F, Ferreira D, Rania VS, Kumara BR, Appa Rao AV. Structurally unique biflavonoids from Selaginella chrysocaulos and Selaginella bryopteris . Chem Biodivers 2006; 3: 405-413
    CrossrefPubMedSearch in Google Scholar
  • 12 Liu HF, Yang JL, Du FF, Gao XM, Ma XT, Huang YH, Xu F, Niu W, Wang FQ, Mao Y, Sun Y, Lu T, Liu CX, Zhang BL, Li C. Absorption and disposition of ginsenosides after oral administration of Panax notoginseng extract to rats. Drug Metab Dispos 2009; 37: 2290-2298
    CrossrefPubMedSearch in Google Scholar
  • 13 Markham KR, Sheppard C, Geiger H. 13 C NMR studies of some naturally occurring amentoflavone and hinokiflavone biflavonoids. Phytochem 1987; 26: 3335-3337
    CrossrefPubMedSearch in Google Scholar
  • 14 He K, Timmermann BN, Aladesanmi AJ, Zeng L. A biflavonoid from Dysoxylum lenticellare Gillespie. Phytochem 1996; 42: 1199-1201
    CrossrefPubMedSearch in Google Scholar
  • 15 Cheng XL, Ma SC, Yu JD, Yang SY, Xiao XY, Hu JY, Lu Y, Shaw PC, But PP, Lin RC. Selaginellin A and B, two novel natural pigments isolated from Selaginella tamariscina . Chem Pharm Bull 2008; 56: 982-984
    CrossrefPubMedSearch in Google Scholar
  • 16 Seeger T, Geiger H, Zinsmeister HD, Frahm JP, Witte L. Biflavonoids from the moss Homalothecium lutescens . Phytochem 1993; 34: 295-296
    CrossrefPubMedSearch in Google Scholar
  • 17 Silva GL, Chai H, Gupta MP, Farnsworth NR, Cordell GA, Pezzuto JM, Beecher CW, Kinghorn AD. Cytotoxic biflavonoids from Selaginella willdenowii . Phytochemistry 1995; 40: 129-134
    CrossrefPubMedSearch in Google Scholar
  • 18 Yang F, Xu KP, Shen J, Li FS, Zou H, Zhou MC, Tan GS. Anthraquinones and biflavonoids from Selaginella delicatula . Chem Nat Compd 2011; 47: 627-629
    CrossrefPubMedSearch in Google Scholar
  • 19 Beckmann S, Geiger H, Pfleiderer WG. Biflavone und 2, 3-dihydrobiflavone aus Metasequoia glyptostroboides . Phytochem 1971; 10: 2465-2474
    CrossrefPubMedSearch in Google Scholar
  • 20 Sobha Rani M, Venkata Rao C, Gunasekar D, Blond A, Bodo B. A biflavonoid from Cycas beddomei . Phytochemistry 1998; 47: 319-321
    CrossrefPubMedSearch in Google Scholar
  • 21 Liao S, Ren QX, Yang CP, Zhang TH, Li JL, Wang XY, Qu XY, Zhang XJ, Zhang ZQ, Wang SQ. Liquid chromatography-tandem mass spectrometry determination and pharmacokinetic analysis of amentoflavone and its conjugated metabolites in rats. J Agric Food Chem 2015; 63: 1957-1966
    CrossrefPubMedSearch in Google Scholar
  • 22 Colovic M, Fracasso C, Caccia S. Brain-to-plasma distribution ratio of the biflavone amentoflavone in the mouse. Drug Metab Lett 2008; 2: 90-94
    CrossrefPubMedSearch in Google Scholar
  • 23 Tetko IV, Gasteiger J, Todeschini R, Mauri A, Livingstone D, Ertl P, Palyulin VA, Radchenko EV, Zefirov NS, Makarenko AS, Tanchuk VY, Prokopenko VV. Virtual computational chemistry laboratory – design and description. J Comput Aided Mol Des 2005; 19: 453-463
    CrossrefPubMedSearch in Google Scholar
  • 24 VCCLAB (Virtual Computational Chemistry Laboratory). Available at. http://www.vcclab.org Accessed September 16, 2015
    PubMed
  • 25 Molinspiration Cheminformatics web services. Available at. http://www.molinspiration.com Accessed September 16, 2015
    PubMed
  • 26 Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 1997; 46: 3-26
    PubMedSearch in Google Scholar
  • 27 Wu X, Sun JG, Peng Y, Liang Y, Wang GJ, Chen H, Wu JZ, Zhang P. Pharmacokinetics, tissue distribution and excretion of verticinone from F. hupehensis in rats. Molecules 2014; 19: 20613-20626
    CrossrefPubMedSearch in Google Scholar