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Planta Med 2013; 79(03/04): 275-280
DOI: 10.1055/s-0032-1328202
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Single Oral Dose Pharmacokinetics of Decursin, Decursinol Angelate, and Decursinol in Rats

Li Li   *
1   Department of Biomedical Sciences, Texas Tech University Health Sciences Center (TTUHSC), School of Pharmacy, Amarillo, Texas, USA
,
Jinhui Zhang   *
1   Department of Biomedical Sciences, Texas Tech University Health Sciences Center (TTUHSC), School of Pharmacy, Amarillo, Texas, USA
,
Chengguo Xing
2   Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA
,
Sung-Hoon Kim
3   Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyunghee University, Seoul, Republic of Korea
,
Junxuan Lü
1   Department of Biomedical Sciences, Texas Tech University Health Sciences Center (TTUHSC), School of Pharmacy, Amarillo, Texas, USA
› Author Affiliations
Further Information

Publication History

received 02 November 2012
revised 08 January 2013

accepted 09 January 2013

Publication Date:
30 January 2013 (online)

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Abstract

Decursin and decursinol angelate are the major components in the alcoholic extract of the root of Angelica gigas Nakai. Our previous work convincingly demonstrated that both decursin and decursinol angelate were rapidly converted to decursinol in mice after administration by either oral gavage or i. p. injection. In the current study, we compared for the first time the plasma profiles of decursinol, when equal moles of decursin/decursinol angelate or decursinol were given to rats by oral gavage, and investigated the effect of different formulas and other chemicals in Angelica gigas extract on the bioavailability of decursinol. Our results show that gavage of decursinol led to a faster attainment of plasma decursinol peak (Tmax ~ 0.7 h) and much higher peak levels than an equal molar amount administered as decursin/decursinol angelate mixture or as Angelica gigas ethanol extract, resulting in 2–3 fold higher bioavailability as estimated by the area under the curve of the respective regimens (65 012 vs. 27 033 h · ng/mL for decursinol and decursin/decursinol angelate treatment groups, respectively). Compared to a formula based on ethanol-PEG400-Tween80, carboxyl methyl cellulose was a less optimized vehicle. In addition, we detected peak levels of decursin and decursinol angelate in the plasma of rats administered with decursin/decursinol angelate or Angelica gigas extract in the nM range (Tmax ~ 0.5 h) with a newly established sensitive UHPLC-MS/MS method. Furthermore, our data support the liver, instead of intestine, as a major organ site where decursin and decursinol angelate were hydrolyzed to decursinol with a S9 microsomal in vitro metabolism assay. Taken together, our study provided important PK, LC-MS/MS methodology, formulation and metabolism insights in a rodent model for the rational design of in vivo efficacy studies of the corresponding chemicals in the future.

Key words

decursin - decursinol angelate - decursinol - Angelica gigas - Apiaceae - LC-MS/MS

* These authors contributed equally to this work and should be considered co-first authors.


Supporting Information

 

  • References

  • 1 Sarker SD, Nahar L. Natural medicine: the genus Angelica . Curr Med Chem 2004; 11: 1479-1500
    CrossrefPubMedGoogle Scholar
  • 2 Lu J, Kim SH, Jiang C, Lee H, Guo J. Oriental herbs as a source of novel anti-androgen and prostate cancer chemopreventive agents. Acta Pharmacol Sin 2007; 28: 1365-1372
    CrossrefPubMedGoogle Scholar
  • 3 Ahn MJ, Lee MK, Kim YC, Sung SH. The simultaneous determination of coumarins in Angelica gigas root by high performance liquid chromatography-diode array detector coupled with electrospray ionization/mass spectrometry. J Pharm Biomed Anal 2008; 46: 258-266
    CrossrefPubMedGoogle Scholar
  • 4 Zhang J, Li L, Jiang C, Xing C, Kim SH, Lu J. Anti-cancer and other bioactivities of Korean Angelica gigas Nakai (AGN) and its major pyranocoumarin compounds. Anticancer Agents Med Chem 2012; 12: 1239-1254
    CrossrefPubMedGoogle Scholar
  • 5 Lee HJ, Lee EO, Lee JH, Lee KS, Kim KH, Kim SH, Lu J. In vivo anti-cancer activity of Korean Angelica gigas and its major pyranocoumarin decursin. Am J Chin Med 2009; 37: 127-142
    CrossrefPubMedGoogle Scholar
  • 6 Li L, Zhang J, Shaik AA, Zhang Y, Wang L, Xing C, Kim SH, Lu J. Quantitative determination of decursin, decursinol Angelate, and decursinol in mouse plasma and tumor tissue using liquid-liquid extraction and HPLC. Planta Med 2012; 78: 252-259
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Park HS, Kim B, Oh JH, Kim YC, Lee YJ. First-pass metabolism of decursin, a bioactive compound of Angelica gigas, in rats. Planta Med 2012; 78: 909-913
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Lee JK, Choi SS, Lee HK, Han KJ, Han EJ, Suh HW. Effects of ginsenoside Rd and decursinol on the neurotoxic responses induced by kainic acid in mice. Planta Med 2003; 69: 230-234
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Seo YJ, Kwon MS, Park SH, Sim YB, Choi SM, Huh GH, Lee JK, Suh HW. The analgesic effect of decursinol. Arch Pharm Res 2009; 32: 937-943
    CrossrefPubMedGoogle Scholar
  • 10 Song JS, Chae JW, Lee KR, Lee BH, Choi EJ, Ahn SH, Kwon KI, Bae MA. Pharmacokinetic characterization of decursinol derived from Angelica gigas Nakai in rats. Xenobiotica 2011; 41: 895-902
    CrossrefPubMedGoogle Scholar
  • 11 Lee S, Lee YS, Jung SH, Shin KH, Kim BK, Kang SS. Anti-tumor activities of decursinol angelate and decursin from Angelica gigas . Arch Pharm Res 2003; 26: 727-730
    CrossrefPubMedGoogle Scholar
  • 12 Son SH, Park KK, Park SK, Kim YC, Kim YS, Lee SK, Chung WY. Decursin and decursinol from Angelica gigas inhibit the lung metastasis of murine colon carcinoma. Phytother Res 2011; 25: 959-964
    CrossrefPubMedGoogle Scholar
  • 13 Jiang C, Lee HJ, Li GX, Guo JM, Malewicz B, Zhao Y, Lee EO, Lee JH, Kim MS, Kim SH, Lu JX. Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation: Identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer. Cancer Res 2006; 66: 453-463
    CrossrefPubMedGoogle Scholar
  • 14 Jung MH, Lee SH, Ahn EM, Lee YM. Decursin and decursinol angelate inhibit VEGF-induced angiogenesis via suppression of the VEGFR-2-signaling pathway. Carcinogenesis 2009; 30: 655-661
    CrossrefPubMedGoogle Scholar
  • 15 Jiang C, Guo J, Wang Z, Xiao B, Lee HJ, Lee EO, Kim SH, Lu J. Decursin and decursinol angelate inhibit estrogen-stimulated and estrogen-independent growth and survival of breast cancer cells. Breast Cancer Res 2007; 9: R77
    CrossrefPubMedGoogle Scholar
  • 16 Park RJ, Kim NJ, Lee KT, Seo SH. Comparative studies on concentration of decursinol in plasma after oral administration of Angelicae Gigantis Radix extract and combined use of Decursin and Cnidii Rhizoma extract or Bupleuri Radix extract in rats. Kor J Pharmacognosy 2001; 32: 72-78
    PubMedGoogle Scholar
  • 17 Kang SY, Lee KY, Park MJ, Kim YC, Markelonis GJ, Oh TH. Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice. Neurobiol Learn Mem 2003; 79: 11-18
    CrossrefPubMedGoogle Scholar
  • 18 Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995; 12: 413-420
    CrossrefPubMedGoogle Scholar
  • 19 Jia L, Liu X. The conduct of drug metabolism studies considered good practice (II): in vitro experiments. Curr Drug Metab 2007; 8: 822-829
    CrossrefPubMedGoogle Scholar
  • 20 van de Kerkhof EG, de Graaf IA, Groothuis GM. In vitro methods to study intestinal drug metabolism. Curr Drug Metab 2007; 8: 658-675
    CrossrefPubMedGoogle Scholar