Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
권호 표지
DOI QR코드

DOI QR Code

Improvement of Hydrolysis and Bioavailability of Coprecipitated Products of Coptidis Rhizoma and Scutellariae Radix by β-Glucuronidase

베타-글루쿠로니다제에 의한 황련.황금 공침물의 가수분해 및 생체이용률 증가

  • Published : 2003.06.20
Download PDF
⟨ Previous Next ⟩

Abstract

During the preparation of decoction from the mixture of Coptidis Rhizoma and Scutellariae Radix, insoluble copreciptate was formed. The coprecipitated product (COP) was composed of berberine and baicalin which was the active ingredient of Coptidis Rhizoma and Scutellariae Radix, respectively. COP was slightly soluble in water and could not be well absorbed after oral administration. This poor bioavailibility might be associated with its poor aqueous solubility. With the purpose of increasing the solubility and bioavailibility of COP, hydrolysis of COP by ${\beta}-glucuronidase$ was carried out. Hydrolyzed products (HOP) of COP were identified and assayed for active ingredients. The partition coefficient study, in situ absorption test, and pharmacokinetic study after oral administration were also performed. COP was found to be consisted of berberine and baicalin with molecular ratio of 1 to 1. This compound was hydrolyzed to berberine and baicalin by ${\beta}-glucuronidase$. The rate of hydrolysis was higher at higher temperature up to $50^{\circ}C$ and higher concentration of ${\beta}-glucuronidase$ up to 2500 unit under our experimental conditions. Baicalein, which is more liphophilic than baicalin, showed greater absorption in small intestine than baicalin did. The plasma concentrations of berberine and baicalein after oral administration of HOP were significantly higer than those of COP. The possible mechanism of increased bioavailibility of berberine and baicalein could be the hydrolysis of COP by ${\beta}-glucuronidase$. On the basis of the above results, it might be said that HOP should be a suitable preparation for increasing the bioavailibility of Coptidis Rhizoma and Scutellariae Radix.

Keywords

References

  1. K. Yasukawa, M. Takido, T. Lkedawa, F. Shimada, M.Takeuchi and S. Nakagawa, Relative inhibitory activity of berberine-type alkaloids against tetradecanoylphorbol-13acetate-induced inflammation, Pharm. Bull., 39(6), 1462-1465(1991) https://doi.org/10.1248/cpb.39.1462
  2. A.H. Amin, K.M. Abbasi and T.V Subbaiah, Berberine sulfate,antimicrobial activity, bioassay and mode of action, Can. J. Microbiol., 15, 1067-1076 (1976). https://doi.org/10.1139/m69-190
  3. T. Sawada, J. Yamahara, K. Goto and M, Yamamura, Studies on the evaluation of crude drugs by Bioassay(IV), Shoyakugakuzasshi, 25(2), 74-78 (1971).
  4. H. Fuijimura, T. Sawada and M. Goto, Screening test of antiinflammatory action on the constituents of crude drugs and plants, Yakugaku Zasshi, 90(6), 782-783 (1970). https://doi.org/10.1248/yakushi1947.90.6_782
  5. S. Bova, R. Padrini, W.F. Goldman, D.M. Berman and G. Cargnelli, On the mechanism of vasodilating action of berberine:possible inositol liqid signaling system, J. Pharmacol. Exp. Ther. Apr; 261(1), 318-323 (1992)
  6. M.H. Akhter, M. Sabir and W.K. Bhide, Possible mechanism of antidiarrheal effect of berberine, Indian J. Med. Res., 70, 233-241 (1979)
  7. W.A. Creasey, Biochemical effect of berberine, Biochem. pharmacol., 28, 1081-1084 (1979) https://doi.org/10.1016/0006-2952(79)90308-3
  8. M. Noguchi, Studies on the pharmaceutical quality of crude drug precipitations used in orient medicine 'kampoo'(II), Chern. Pharm. Bull., 26(9), 2624-2629 (1971).
  9. N. Mori and T. Toyama, Berberine glycyrrhizinate, Japan, 1394(67), (C1.30)(2). Jan. 23, Appl. 3 (1965).
  10. T. Hayashi, M. Kubo and E. Noguchi, Antiinflammatory and antiulcer berberine glycyrrhizinate, Japan Kokai, 7862. 1871(Ce. Co 7D445/00), 05 (1978).
  11. Sawada, et al. 日本公定書協會會誌, 16, 7 (1966)
  12. J.H. Yang, Studies on bioavailability of berberine pamoate(1), J. Kor. Pharm., Sci., 16(2), 78-84 (1986).
  13. S. Takaki ,M. Yamaki and K. Inoue, Studies on the water soluble constituents of the roots of Scutellaria baicalensis, Yakugaku Zasshi., 100(12), 1220-1224 (1980) https://doi.org/10.1248/yakushi1947.100.12_1220
  14. T. Tomimori, Y. Miyaichi and Y. Imoto, Studies on the constituents of Scutellaria Species (2), Yakugaku Zasshi.,103(6), 607-611 (1983) https://doi.org/10.1248/yakushi1947.103.6_607
  15. T. Tomimori, Y. Miyaichi and Y. Imoto, Studies on the constituents of Scutellaria Species (3), Yakugaku Zasshi.,104(5), 524-528 (1984) https://doi.org/10.1248/yakushi1947.104.5_524
  16. T. Tomimori, Y. Miyaichi and Y. Imoto, Studies on the constituents of Scutellaria Species (3), Yakugaku Zasshi., 104(5), 529-534 (1984) https://doi.org/10.1248/yakushi1947.104.5_529
  17. Y. Takino, T. Miyahara and E. Arichi, Determination of some flavonoids in Scutellariae Radix by HPLC, Chern. Pharm. Bull., 35(8), 3494-3497 (1987) https://doi.org/10.1248/cpb.35.3494
  18. K.J. Choi, S.R. Ko and J.W Yang, Identification. of index components of Scutellariae Radix and quanntative determination of baicalin from crude drug preparation, Kor. J. Pharmcogn., 21(2), 158-162 (1990).
  19. Y. Kimura, M. Kubo and T. Tani, Studies on Scutellariae Radix (3), Effects on lipid metabolism in serum, liver and fat cells of rats, Chern. Pharm. Bull., 29(8), 2308-2312 (1981) https://doi.org/10.1248/cpb.29.2308
  20. Y. Kimura, M. Kubo and T. Tani, Studies on Scutellariae Radix (4), Effects on lipid peroxidation in rat liver, Chern. Pharm. Bull., 29(9), 2610-2617 (1981). https://doi.org/10.1248/cpb.29.2610
  21. Y. Kimura, M. Kubo and K. Kusaka, Studies on .Scutellariae Radix (5), Effects on ethanol-induced hyperlipemia and lipolysis in isolated fat cells, Chern. Pharm. Bull., 30(1), 219222 (1982). https://doi.org/10.1248/cpb.30.219
  22. D.H. Kim, I.S. lang, H.K. Lee, E.A. lung and K.Y. Lee, Metabolism of glycyrrhizin and baicalin by human mtestmal bacteria, Arch. Pharm. Res., 19(4), 292-296 (1996) https://doi.org/10.1007/BF02976243
  23. T. Tanaka, K. Metori S. Mineo, M. Hirotani, T. Furuya and S. Kobayashi, Inhibitory effects of berberine-type alkaloids in elastase, Planta Med., 59(3), 200-2002 (1993) https://doi.org/10.1055/s-2006-959651
  24. T. Higuchi and K.A. Connors, Phase solubility technics, Adv. Anal. Chern. Instr; 117-212 (1965)
  25. W.H. Barr and S. Riegelman, Intestinal drug absorption and metabolism I. Comparison of method and models to study physicological factors of in vitro and in vivo intestinal absorption, J. Pharrn. Sci., 59(2), 154-163 (1970). https://doi.org/10.1002/jps.2600590204
  26. Y. Ozaki, H. Suzuki and M. Satake, Comparative studies on concentration of berberine in plasma after oral administration of Coptis Rhizoma extract, Yakugaku Zasshi., 113(1), 63-69(1996)