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Role of metabolism by intestinal microbiota in pharmacokinetics of oral baicalin

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Abstract

Baicalin (baicalein-7-glucuronide) is a flavonoid purified from Scutellaria baicalensis Georgi that has traditionally been used for treatment of hypertension, cardiovascular diseases, and viral hepatitis. In this study, the effects of intestinal microbiota on the pharmacokinetics of baicalin were investigated in normal and antibiotic-pretreated rats following p.o. administration of 100 mg/kg baicalin by using liquid chromatography/ion trap mass spectrometry. When rats were pretreated orally with cefadroxil, oxytetracycline and erythromycin for 3 days to control the number of intestinal bacteria, the pharmacokinetic parameters of oral baicalin were significantly affected by antibiotics: Cmax, T1/2(β), Kel and AUC values were significantly changed compared to those in normal rats. These results indicate that intestinal microbiota might play a key role in the oral pharmacokinetics of baicalin.

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References

  • Abe, K., O. Inoue, and E. Yumioka. 1990. Biliary excretion of metabolites of baicalin and baicalein in rats. Chemical and Pharmaceutical Bulletin (Tokyo) 38: 209–211.

    CAS  Google Scholar 

  • Blaut, M. 2002. Relationship of prebiotics and food to intestinal microflora. European Journal of Nutrition 41(Suppl 1): 11–16.

    Google Scholar 

  • Chen, X., H. Wang, Y. Du, and D. Zhong. 2002. Quantitation of the flavonoid wogonin and its major metabolite wogonin-7β-D-glucuronide in rat plasma by liquid chromatography-tandem mass spectrometry. Journal of Chromatography B Analytical Technologies in the Biomedical and Life Sciences 775: 169–178.

    Article  CAS  Google Scholar 

  • Chiou, W.L. 1978. Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level–time curve. Journal of Pharmacokinetics and Biopharmaceutics 6: 539–546.

    Article  CAS  PubMed  Google Scholar 

  • Feng, N.P., B. Di, and W.Y. Liu. 2005. Comparison of the metabolism of baicalin in rats orally administered with Radix scutellariae extract and Shuang-Huang-Lian extract. Chemical and Pharmaceutical Bulletin (Tokyo) 53: 978–983.

    Article  CAS  Google Scholar 

  • Guo, H.X., D.H. Liu, Y. Ma, J.F. Liu, Y. Wang, Z.Y. Du, X. Wang, J.K. Shen, and H.L. Peng. 2009. Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet. Acta Pharmacologica Sinica 30: 1505–1512.

    Article  CAS  PubMed  Google Scholar 

  • Ikemoto, S., K. Sugimura, N. Yoshida, R. Yasumoto, S. Wada, K. Yamamoto, and T. Kishimoto. 2000. Antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines. Urology 55: 951–955.

    Article  CAS  PubMed  Google Scholar 

  • Jeong, H.G., M.J. Kang, H.G. Kim, G. Oh Do, J.S. Kim, S.K. Lee, and T.C. Jeong. 2013. Role of intestinal microflora in xenobiotic-induced toxicity. Molecular Nutrition and Food Research 57: 84–99.

    Article  CAS  PubMed  Google Scholar 

  • Jin, M.J., U. Kim, I.S. Kim, Y. Kim, D.H. Kim, S.B. Han, O.S. Kwon, and H.H. Yoo. 2010. Effects of gut microflora on pharmacokinetics of hesperidin: a study on non-antibiotic and pseudo-germ-free rats. Journal of Toxicology and Environmental Health A 73: 1441–1450.

    Article  CAS  Google Scholar 

  • Kakimoto, K., A. Toriba, T. Ohno, M. Ueno, T. Kameda, N. Tang, and K. Hayakawa. 2008. Direct measurement of the glucuronide conjugate of 1-hydroxypyrene in human urine by using liquid chromatography with tandem mass spectrometry. Journal of Chromatography B Analytical Technologies in the Biomedical and Life Sciences 867: 259–263.

    Article  CAS  Google Scholar 

  • Kang, M.J., H.W. Ha, H.G. Kim, D.H. Lee, M.J. Kong, Y.T. Ahn, D.H. Kim, B.S. Shin, W. Kang, H.G. Jeong, and T.C. Jeong. 2011. Role of metabolism by intestinal bacteria in arbutin-induced toxicity in vitro. Archives of Pharmacal Research 34: 687–693.

    Article  CAS  PubMed  Google Scholar 

  • Kim, D.H., E.A. Jung, I.S. Sohng, J.A. Han, T.H. Kim, and M.J. Han. 1998. Intestinal bacterial metabolism of flavonoids and its relation to some biological activities. Archives of Pharmacal Research 21: 17–23.

    Article  CAS  PubMed  Google Scholar 

  • Kim, Y.S., J.J. Kim, K.H. Cho, W.S. Jung, S.K. Moon, E.K. Park, and D.H. Kim. 2008. Biotransformation of ginsenoside Rb1, crocin, amygdalin, geniposide, puerarin, ginsenoside Re, hesperidin, poncirin, glycyrrhizin, and baicalin by human fecal microflora and its relation to cytotoxicity against tumor cells. Journal of Microbiology and Biotechnology 18: 1109–1114.

    CAS  PubMed  Google Scholar 

  • Kitamura, K., M. Honda, H. Yoshizaki, S. Yamamoto, H. Nakane, M. Fukushima, K. Ono, and T. Tokunaga. 1998. Baicalin, an inhibitor of HIV-1 production in vitro. Antiviral Research 37: 131–140.

    Article  CAS  PubMed  Google Scholar 

  • Liu, G., J. Ma, Y. Chen, Q. Tian, Y. Shen, X. Wang, B. Chen, and S. Yao. 2009. Investigation of flavonoid profile of Scutellaria bacalensis Georgi by high performance liquid chromatography with diode array detection and electrospray ion trap mass spectrometry. Journal of Chromatography A 1216: 4809–4814.

    Article  CAS  PubMed  Google Scholar 

  • Muto, R., T. Motozuka, M. Nakano, Y. Tatsumi, F. Sakamoto, and N. Kosaka. 1998. The chemical structure of new substance as the metabolite of baicalin and time profiles for the plasma concentration after oral administration of sho-saiko-to in human. Yakugaku Zasshi 118: 79–87.

    CAS  PubMed  Google Scholar 

  • Shen, Y.C., W.F. Chiou, Y.C. Chou, and C.F. Chen. 2003. Mechanisms in mediating the anti-inflammatory effects of baicalin and baicalein in human leukocytes. European Journal of Pharmacology 465: 171–181.

    Article  CAS  PubMed  Google Scholar 

  • Shieh, D.E., L.T. Liu, and C.C. Lin. 2000. Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. Anticancer Research 20: 2861–2865.

    CAS  PubMed  Google Scholar 

  • Sousa, T., R. Paterson, V. Moore, A. Carlsson, B. Abrahamsson, and A.W. Basit. 2008. The gastrointestinal microbiota as a site for the biotransformation of drugs. International Journal of Pharmaceutics 363: 1–25.

    Article  CAS  PubMed  Google Scholar 

  • Taiming, L., and J. Xuehua. 2006. Investigation of the absorption mechanisms of baicalin and baicalein in rats. Journal of Pharmaceutical Sciences 95: 1326–1333.

    Article  PubMed  Google Scholar 

  • Trinh, H.T., E.H. Joh, H.Y. Kwak, N.I. Baek, and D.H. Kim. 2010. Anti-pruritic effect of baicalin and its metabolites, baicalein and oroxylin A, in mice. Acta Pharmacologica Sinica 31: 718–724.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, L., G. Lin, and Z. Zuo. 2007. Involvement of UDP-glucuronosyltransferases in the extensive liver and intestinal first-pass metabolism of flavonoid baicalein. Pharmaceutical Research 24: 81–89.

    Article  PubMed  Google Scholar 

  • Zuo, F., N. Nakamura, T. Akao, and M. Hattori. 2006. Pharmacokinetics of berberine and its main metabolites in conventional and pseudo germ-free rats determined by liquid chromatography/ion trap mass spectrometry. Drug Metabolism and Disposition 34: 2064–2072.

    Article  CAS  PubMed  Google Scholar 

  • Zuo, F., Z.M. Zhou, M.Z. Yan, M.L. Liu, Y.L. Xiong, Q. Zhang, H.Y. Song, and W.H. Ye. 2002. Metabolism of constituents in Huangqin-Tang, a prescription in traditional Chinese medicine, by human intestinal flora. Biological and Pharmaceutical Bulletin 25: 558–563.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by grants from Korea Food & Drug Administration (09172KFDA996), National Research Foundation of Korea (2010-0026220), and Yeungnam University (211-A-345-014 for Dr. M.J. Kang).

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Authors and Affiliations

  1. College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan, 712-749, South Korea

    Mi Jeong Kang, Gyu Sub Ko, Do Gyeong Oh, Jin Sung Kim, Keumhan Noh, Wonku Kang & Tae Cheon Jeong

  2. Korea Research Institute of Bioscience and Biotechnology, Ochang, South Korea

    Won Ki Yoon & Hyoung Chin Kim

  3. College of Pharmacy, Chungnam National University, Daejeon, South Korea

    Hye Gwang Jeong

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  1. Mi Jeong Kang
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  2. Gyu Sub Ko
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  3. Do Gyeong Oh
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  4. Jin Sung Kim
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  5. Keumhan Noh
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  6. Wonku Kang
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  7. Won Ki Yoon
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  9. Hye Gwang Jeong
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  10. Tae Cheon Jeong
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Correspondence to Tae Cheon Jeong.

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Kang, M.J., Ko, G.S., Oh, D.G. et al. Role of metabolism by intestinal microbiota in pharmacokinetics of oral baicalin. Arch. Pharm. Res. 37, 371–378 (2014). https://doi.org/10.1007/s12272-013-0179-2

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  • DOI: https://doi.org/10.1007/s12272-013-0179-2

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