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A comparison of the pharmacokinetics of three different preparations of total flavones of Hippophae rhamnoides in beagle dogs after oral administration

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Abstract

Pharmacokinetic properties of isorhamnetin, quercetin, and kaempferol in three different total flavones of Hippophae rhamnoides (TFH) preparations were compared after oral administration to beagle dogs by a UPLC–MS method. The pharmacokinetic results showed that C max of isorhamnetin and quercetin in TFH solid dispersion (TFH-SD) and TFH self-emulsifying (TFH-SE) preparations was significantly enhanced than that in TFH preparations (p < 0.05). The AUCs of isorhamnetin and quercetin in TFH-SD were 5.9- and 3.1-fold higher than that of TFH, while the AUCs of isorhamnetin and quercetin in TFH-SE were 3.4- and 2.4-fold higher than that of TFH. These findings suggested that the oral bioavailability of isorhamnetin and quercetin in beagle dogs can be significantly increased in TFH-SD and TFH-SE preparations compared to TFH preparations, which was helpful to explore the new forms for oral administration TFH and explain their in vivo processes.

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References

  • Alexopoulou E, Georgopoulos A, Kagkadis KA, Demetzos C (2006) Preparation and characterization of lyophilized liposomes with incorporated quercetin. J Liposome Res 16:17–25

    Article  CAS  PubMed  Google Scholar 

  • Basu M, Prasad R, Jayamurthy P, Pal K, Arumughan C, Sawhney RC (2007) Anti-atherogenic effects of seabuckthorn (Hippophaea rhamnoides) seed oil. Phytomedicine 14:770–777

    Article  CAS  PubMed  Google Scholar 

  • Bose S, Michniak-Kohn B (2012) Preparation and characterization of lipid based nanosystems for topical delivery of quercetin. Eur J Pharm Sci 48:442–452

    Article  PubMed  Google Scholar 

  • Cermak R, Landgraf S, Wolffram S (2003) The bioavailability of quercetin in pigs depends on the glycoside moiety and on dietary factors. J Nutr 133:2802–2807

    CAS  PubMed  Google Scholar 

  • Chauhan AS, Negi PS, Rarnteke RS (2007) Antioxidant and antibacterial activities of aqueous extract of Seabuckthorn (Hippophae rhamnoides) seeds. Fitoterapia 78:590–592

    Article  PubMed  Google Scholar 

  • Cornaire G, Woodley J, Hermann P, Cloarec A, Arellano C, Houin G (2004) Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo. Int J Pharm 278:119–131

    Article  CAS  PubMed  Google Scholar 

  • Costa ARD, Marquiafavel FS, Vaz MMDLL, Rocha BA, Bueno PCP, Amaral PLM, Barud HD, Berreta-Silva AA (2011) Quercetin-PVP K25 solid dispersions: preparation, thermal characterization and antioxidant activity. J Therm Anal Calorim 104:273–278

    Article  CAS  Google Scholar 

  • Gugler R, Leschik M, Dengler HJ (1975) Disposition of quercetin in man after single oral and intravenous doses. Eur J Clin Pharmacol 9:229–234

    Article  CAS  PubMed  Google Scholar 

  • Hsu YW, Tsai CF, Chen WK, Lu FJ (2009) Protective effects of seabuckthorn (Hippophae rhamnoides L.) seed oil against carbon tetrachloride-induced hepatotoxicity in mice. Food Chem Toxicol 47:2281–2288

    Article  CAS  PubMed  Google Scholar 

  • Iosio T, Voinovich D, Perissutti B, Serdoz F, Hasa D, Grabnar I, Acqua SD, Zara GP, Muntoni E, Pinto JF (2011) Oral bioavailability of silymarin phytocomplex formulated as self-emulsifying pellets. Phytomedicine 18:505–512

    Article  CAS  PubMed  Google Scholar 

  • Kakran M, Shegokar R, Sahoo NG, Shaal LA, Li L, Muller RH (2012) Fabrication of quercetin nanocrystals: comparison of different methods. Eur J Pharm Biopharm 80:113–121

    Article  CAS  PubMed  Google Scholar 

  • Khaled KA, El-Sayed YM, Al-Hadiya BM (2003) Disposition of the flavonoid quercetin in rats after single intravenous and oral doses. Drug Dev Ind Pharm 29:397–403

    Article  CAS  PubMed  Google Scholar 

  • Li W, Yi S, Wang Z, Chen S, **n S, **e J, Zhao C (2011) Self-nanoemulsifying drug delivery system of persimmon leaf extract: optimization and bioavailability studies. Int J Pharm 420:161–171

    Article  CAS  PubMed  Google Scholar 

  • Maheshwari DT, Kumar MSY, Verma SK, Singh VK, Singh SN (2011) Antioxidant and hepatoprotective activities of phenolic rich fraction of Seabuckthorn (Hippophae rhamnoides L.) leaves. Food Chem Toxicol 49:2422–2428

    Article  CAS  PubMed  Google Scholar 

  • Martignoni M, Groothuis GM, de Kanter R (2006) Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin Drug Metab Toxicol 2:875–894

    Article  CAS  PubMed  Google Scholar 

  • Moon YJ, Wang L, DiCenzo R, Morris ME (2008) Quercetin pharmacokinetics in humans. Biopharm Drug Dispos 29:205–217

    Article  CAS  PubMed  Google Scholar 

  • Morand C, Manach C, Crespy V, Remesy C (2000) Quercetin 3-O-beta-glucoside is better absorbed than other quercetin forms and is not present in rat plasma. Free Radic Res 33:667–676

    Article  CAS  PubMed  Google Scholar 

  • Ofer M, Wolffram S, Koggel A, Spahn-Langguth H, Langguth P (2005) Modulation of drug transport by selected flavonoids: involvement of P-gp and OCT? Eur J Pharm Sci 25:263–271

    Article  CAS  PubMed  Google Scholar 

  • Piskula MK (2000) Factors affecting flavonoids absorption. BioFactors 12:175–180

    Article  CAS  PubMed  Google Scholar 

  • Plotas P, Anastasopoulos C, Makri OE, Leotsinidis M, Georgakopoulos CD (2014) A UPLC–MS method for the determination of ofloxacin concentrations in aqueous humor. Anal Chem Insights 9:27–32

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rangel-Ordonez L, Noldner M, Schubert-Zsilavecz M, Wurglics M (2010) Plasma levels and distribution of flavonoids in rat brain after single and repeated doses of standardized Ginkgo biloba extract EGb 761®. Planta Med 76:1683–1690

    Article  CAS  PubMed  Google Scholar 

  • Reinboth M, Wolffram S, Abraham G, Ungemach FR, Cermak R (2010) Oral bioavailability of quercetin from different quercetin glycosides in dogs. Br J Nutr 104:198–203

    Article  CAS  PubMed  Google Scholar 

  • Shi R, Qiao S, Yu DQ, Shi XW, Liu M, Jiang XJ, Wang Q, Zhang LT (2011) Simultaneous determination of five flavonoids from Scutellaria Barbata extract in rat plasma by LC-MS/MS and its application to pharmacokinetic study. J Chromatogr B Anal Technol Biomed Life Sci 879:1625–1632

    Article  CAS  Google Scholar 

  • Shukla SK, Chaudhary P, Kumar IP, Samanta N, Afrin F, Gupta ML, Sharma UK, Sinha AK, Sharma YK, Sharma RK (2006) Protection from radiation-induced mitochondrial and genomic DNA damage by an extract of Hippophae rhamnoides. Environ Mol Mutagen 47:647–656

    Article  CAS  PubMed  Google Scholar 

  • Smith AJ, Kavuru P, Wojtas L, Zaworotko MJ, Shytle RD (2011) Cocrystals of quercetin with improved solubility and oral bioavailability. Mol Pharm 8:1867–1876

    Article  CAS  PubMed  Google Scholar 

  • Sun B, Sun GB, **ao J, Chen RC, Wang X, Wu Y, Cao L, Yang ZH, Sun XB (2012) Isorhamnetin inhibits H(2)O(2)-induced activation of the intrinsic apoptotic pathway in H9c2 cardiomyocytes through scavenging reactive oxygen species and ERK inactivation. J Cell Biochem 113:473–485

    Article  CAS  PubMed  Google Scholar 

  • Tian S, He G, Song J, Wang S, **n W, Zhang D, Du G (2012) Pharmacokinetic study of baicalein after oral administration in monkeys. Fitoterapia 83:532–540

    Article  CAS  PubMed  Google Scholar 

  • Vo CL, Park C, Lee BJ (2013) Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Biopharm 85:799–813

    Article  CAS  PubMed  Google Scholar 

  • Walle T, Otake Y, Walle UK, Wilson FA (2000) Quercetin glucosides are completely hydrolyzed in ileostomy patients before absorption. J Nutr 130:2658–2661

    CAS  PubMed  Google Scholar 

  • Wang Y, Cao J, Zeng S (2005) Involvement of P-glycoprotein in regulating cellular levels of Ginkgo flavonols: quercetin, kaempferol, and isorhamnetin. J Pharm Pharmacol 57:751–758

    Article  CAS  PubMed  Google Scholar 

  • Wang XD, **a HJ, **ng F, Deng GF, Shen Q, Zeng S (2009) A highly sensitive and robust UPLC-MS with electrospray ionization method for quantitation of taxifolin in rat plasma. J Chromatogr B Anal J Mol Biol 877:1778–1786

    Article  CAS  Google Scholar 

  • Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, Porter CJ (2013) Strategies to address low drug solubility in discovery and development. Pharmacol Rev 65:315–499

    Article  PubMed  Google Scholar 

  • Wu J, **ng H, Tang D, Gao Y, Yin X, Du Q, Jiang X, Yang D (2012) Simultaneous determination of nine flavonoids in beagle dog by HPLC with DAD and application of Ginkgo biloba extracts on the pharmacokinetic. Acta Chromatogr 24:627–642

    Article  CAS  Google Scholar 

  • **e Y, Li G, Yuan X, Cai Z, Rong R (2009a) Preparation and in vitro evaluation of solid dispersions of total flavones of Hippophae rhamnoides L. AAPS PharmSciTech 10:631–640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • **e Y, Rong R, Li G, Yuan X, Wang J (2009b) Studies on self-microemulsifying drug preparations of total flavones of Hippophae rhamnoides. Zhongguo Zhong Yao Za Zhi 34:43–46

    CAS  PubMed  Google Scholar 

  • Xu J, Zhang Q, Zhao L, Wang Y, Xue L, Han T, Zheng C, Qin L (2012) Quantitative determination and pharmacokinetic study of casticin in rat plasma by liquid chromatography–mass spectrometry. J Pharm Biomed Anal 61:242–246

    Article  CAS  PubMed  Google Scholar 

  • Yue ME, Jiang TF, Shi YP (2004) Fast determination of flavonoids in Hippophae rhamnoides and its medicinal preparation by capillary zone electrophoresis using dimethyl-beta-cyclodextrin as modifier. Talanta 62:695–699

    Article  CAS  PubMed  Google Scholar 

  • Zhang Q, Cui H (2005) Simultaneous determination of quercetin, kaempferol, and isorhamnetin in phytopharmaceuticals of Hippophae rhamnoides L. by high-performance liquid chromatography with chemiluminescence detection. J Sep Sci 28:1171–1178

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Lin G, Zuo Z (2004) High-performance liquid chromatographic method for simultaneous determination of baicalein and baicalein 7-glucuronide in rat plasma. J Pharm Biomed Anal 36:637–641

    Article  PubMed  Google Scholar 

  • Zhang QY, Kaminsky LS, Dunbar D, Zhang J, Ding X (2007) Role of small intestinal cytochromes p450 in the bioavailability of oral nifedipine. Drug Metab Dispos 35:1617–1623

    Article  CAS  PubMed  Google Scholar 

  • Zhang HS, Zhang M, Yu LH, Zhao Y, He NW, Yang XB (2012) Antitumor activities of quercetin and quercetin-5′,8-disulfonate in human colon and breast cancer cell lines. Food Chem Toxicol 50:1589–1599

    Article  CAS  PubMed  Google Scholar 

  • Zhao G, Duan J, **e Y, Lin G, Luo H, Li G, Yuan X (2013) Effects of solid dispersion and self-emulsifying formulations on the solubility, dissolution, permeability and pharmacokinetics of isorhamnetin, quercetin and kaempferol in total flavones of Hippophae rhamnoides L. Drug Dev Ind Pharm 39:1037–1045

    Article  CAS  PubMed  Google Scholar 

  • Zuo Z, Zhang L, Zhou L, Chang Q, Chow M (2006) Intestinal absorption of hawthorn flavonoids—in vitro, in situ and in vivo correlations. Life Sci 79:2455–2462

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was sponsored by the National Science Foundation of China (81303304), the Innovation Program of Shanghai Municipal Education Commission (14YZ057), the Specialized Research Fund for the Doctoral Program of Higher Education (20133107120006), and the Medical Program of Hongkou District (1301-01).

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    Authors and Affiliations

    1. Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, People’s Republic of China

      **gze Duan, Yang Dang, Houjun Meng, Huizhen Wang & Yan **e

    2. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

      **gze Duan, Houjun Meng, Guowen Li & Tao Wu

    3. Global Pharmaceutical Research and Development, Hospira Inc., 1776 North Centennial Drive, Mcpherson, KS, 67460, USA

      ** Ma

    4. Pharmacy Department, Shanghai TCM-integrated Hospital, Shanghai, 200082, China

      Guowen Li

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    1. **gze Duan
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    Correspondence to Yan **e.

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    J. Duan and Y. Dang have contributed equally to this work.

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    Duan, J., Dang, Y., Meng, H. et al. A comparison of the pharmacokinetics of three different preparations of total flavones of Hippophae rhamnoides in beagle dogs after oral administration. Eur J Drug Metab Pharmacokinet 41, 239–249 (2016). https://doi.org/10.1007/s13318-015-0254-9

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