DOI QR코드

DOI QR Code

Metabolism of Wogonoside by Human Fecal Microflora and Its Anti-pruritic Effect

  • Trinh, Hien-Trung (Department of Pharmaceutical Science and Department of Life and Pharmaceutical Sciences, Kyung Hee University) ;
  • Jang, Seo-Young (Department of Food and Nutrition, Kyung Hee University) ;
  • Han, Myung-Joo (Department of Food and Nutrition, Kyung Hee University) ;
  • Kawk, Ho-Young (Graduate School of Biotechnology and PMRC, Kyung Hee University) ;
  • Baek, Nam-In (Graduate School of Biotechnology and PMRC, Kyung Hee University) ;
  • Kim, Dong-Hyun (Department of Pharmaceutical Science and Department of Life and Pharmaceutical Sciences, Kyung Hee University)
  • Published : 2009.04.30

Abstract

To understand the relationship between the metabolism of wogonoside from the rhizome of Scutellaria baicalensis, and its anti-pruritic effect, we anaerobically incubated it with human fecal microflora, identified its metabolite identified, and investigated its anti-pruritic effect in compound 48/80 or histamineinduced pruritic mice. Wogonoside was metabolized to wogonin, with metabolic activity of $6.9{\pm}5.1\;nmol/h/mg$ wet weight of fecal microflora. Orally administered wogonoside had more potent anti-scratching behavioral effect in compound 48/80 or histamine-treated mice than intraperitoneally treated one, apart from orally administered its metabolite, wogonin, which was more potent than the orally administered one. Wogonoside showed more potent anti-pruritic effects when administered at 5 h prior to the pruritic agent treatment than when administered at 1 h before. However, wogonin orally administered 1 h before the treatment with pruritic agents showed a more potent anti-pruritic effect than when treated at 5 h before. Orally administered wogonoside may be metabolized to wogonin in the intestine and its anti-scratching behavioral effect may be dependent on its metabolism by intestinal microflora.

Keywords

References

  1. Abe, K., Inoue, O. and Yumioka, E. (1990). Biliary excretion of metabolites of baicalin and baicalein in rats. Chem. Pharm. Bull. 38, 209-211
  2. Akao, T., Kawabata, K. and Yanagisawa, E. (2000). Baicalin, the predominant flavone glucuronide of scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form. J. Pharm. Pharmacol. 52, 1563-1568 https://doi.org/10.1211/0022357001777621
  3. Akao, T., Dakashita, Y., Hanada, M., Goto, H., Shimada, Y. and Terasawa, K. (2004). Enteric excretion of baicalein, a flavone of Scutellariae Radix, via glucuronidation in rat: involvement of multidrug resistance-associated protein 2. Pharm. Res. 21, 2120-2126 https://doi.org/10.1023/B:PHAM.0000048205.02478.b5
  4. Akao, T., Kida, H., Kanaoka, M., Hattori, M. and Kobashi, K. (1998). Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1 from Panax ginseng. J. Pharm. Pharmacol. 50, 1155-1160 https://doi.org/10.1111/j.2042-7158.1998.tb03327.x
  5. Chou, T. C., Chang, L. P., Li, C. Y., Wong, C. S. and Yang, S. P. (2003). The antiinflammatory and analgesic effects of baicalin in carrageenan-evoked thermal hyperalgesia. Anesth. Analq. 17, 1724-1729 https://doi.org/10.1213/01.ANE.0000087066.71572.3F
  6. Hagermark, O. (1955). Itch mediators. Semin. Dermatol. 14, 271-276 https://doi.org/10.1016/S1085-5629(05)80047-1
  7. Inagaki, N., Nagao, M., Kawasaki, H., Kim, J. F. and Nagai, H. (2001). Scratching behavior in various strains of mice. Skin Pharmacol. Appl. Skin Physiol. 14, 87-96 https://doi.org/10.1159/000056338
  8. Jang, S. I., Kim, H. J., Hwang, K. M., Jekal, S. J., Pae, H. O., Choi, B. M., Yun, Y. G., Kwon, T. O., Chung, H. T. and Kim, Y. C. (2003). Hepatoprotective effect of baicalin, a major flavone from Scutellaria radix, on acetaminophen-induced liver injury in mice. Immunopharmacol. Immunotoxicol. 25, 585-594 https://doi.org/10.1081/IPH-120026443
  9. Kim, D. H., Cho, K. H., Moon, S. K., Kim, Y. S., Kim, D. H., Choi, J. S. and Chung, H. Y. (2005). Cytoprotective mechanism of baicalin against endothelial cell damage by peroxynitrite. J. Pharm. Pharmacol. 57, 1581-1590 https://doi.org/10.1211/jpp.57.12.0008
  10. Kobashi, K. and Akao, T. (1997). Relation of intestinal bacteria to pharmacological effects of glycosides. Bioscience Microflora 16, 1-7 https://doi.org/10.12938/bifidus1996.16.1
  11. Koda, A., Nagai, H. and Wada, H. (1970). Pharmacological actions of baicalin and baicalein. 2. On passive anaphylaxis. Nippon Yakurigaku Zasshi 66, 237-247 https://doi.org/10.1254/fpj.66.237
  12. Kuraishi, Y., Nagasawa, T., Hayashi, K. and Satoh, M. (1995). Scratching behavior induced by pruritogenic but not algesiogenic agents in mice. Eur. J. Pharmacol. 275, 229-233 https://doi.org/10.1016/0014-2999(94)00780-B
  13. Lee, D. K., Kim, Y. S., Ko, C. N., Cho, K. H., Bae, H. S., Lee, K. S., JKim. J., Park, E. K. and Kim, D. H. (2003). Fecal metabolic activities of herbal components to bioactive compounds. Arch. Pharm. Res. 25, 165-169 https://doi.org/10.1007/BF02976558
  14. Lerner, E. A. (1994) 'Itch: mechanisms and management of pruritis,' ed. By Berhard J., McGraw-Hill, New York, pp 23-25
  15. Liaw, J., Gau, Y. Y. and Chao, Y. C. (1999). Effect of baicalin on tracheal permeability in ovalbumin (OA)-sensitized guinea pigs. Pharm. Res. 16, 1653-1657 https://doi.org/10.1023/A:1011985427736
  16. Lim, B. O. (2003). Effects of wogonin, wogonoside, and 3,5, 7,2',6'-pentahydroxyflavone on chemical mediator production in peritoneal exduate cells and immunoglobulin E of rat mesenteric lymph node lymphocytes. J. Ethnopharmacol. 84, 23-29 https://doi.org/10.1016/S0378-8741(02)00257-X
  17. Lu, T., Song, J., Huang, F., Deng, Y., Xie, L., Wang, G. and Liu, X. (2007). Comparative pharmacokinetics of baicalin after oral administration of pure baicalin, Radix scutellariae extract and Huang-Lian-Jie-Du-Tang to rats. J. Ethnopharmacol. 110, 412-418 https://doi.org/10.1016/j.jep.2006.09.036
  18. Raiford, D. S. (1995). Pruritus of chronic cholestasis. QJM 88, 603-607
  19. Schmeiz, M., Schmidt, R., Bickel, A., Handerker, H. O. and Torebjork, H. E. (1997). Specific C-receptors for itch in human skin. J. Neurosci. 17, 8003-8008
  20. Sugimoto, Y., Umakoshi, K., Nojiri, N. and Kamei, C. (1998). Effects of histamine H1 receptor antagonists on compound 48/80-induced scratching behavior in mice. Eur. J. Pharmacol. 351, 1-5 https://doi.org/10.1016/S0014-2999(98)00288-X
  21. Taniguchi, C., Homma, M., Takano, O., Hirano, T., Oka, K., Aoyagi, Y., Niitsuma, T. and Hayashi, T. (2000). Pharmacological effects of urinary products obtained after treatment with saiboku-to, a herbal medicine for bronchial asthma, on type IV allergic reaction. Planta Med. 66, 607-611 https://doi.org/10.1055/s-2000-8626
  22. Takido, M., Aimi, M., Takahashi, S., Yamamouchi, S., Torii, H. and Dohi, S. (1975). Studies on the constituents in the water extracts of crude drugs. I. On the roots of Scutellaria baicalensis Georgi (Wogon) (1). Yakhagaku Zasshi 95, 108-113 https://doi.org/10.1248/yakushi1947.95.1_108
  23. Tomimori, T., Miyaichi, Y. and Kizu, H. (1982). On the flavonoid constituents from the roots of Scutellaria baicalensis Georgi. I. Yakugaku Zasshi 102, 388-391 https://doi.org/10.1248/yakushi1947.102.4_388
  24. Wu, S., Sun, A. and Liu, R. (2005). Separation and purification of baicalin and wogonoside from the Chinese medicinal plant Scutellaria baicalensis Georgi by high-speed counter-current chromatography. J. Chromatogr. A. 1066, 243-247 https://doi.org/10.1016/j.chroma.2005.01.054
  25. Xing, J., Chen, X. Y. and Zhong, D. F. (2005a). Absorption and enterohepatic circulation of baicalin in rats. Life Sci. 78, 140-146 https://doi.org/10.1016/j.lfs.2005.04.072
  26. Xing, J., Chen, X. Y., Sun, Y. M., Luan, Y. and Zhong, D. F. (2005b). Interaction of baicalin and baicalein with antibiotics in the gastrointestinal tract. J. Pharm. Pharmacol. 57, 743-750 https://doi.org/10.1211/0022357056244
  27. Yim, J. S., Kim, Y. S., Moon, S. K., Cho, K. H., Bae, H. S., Kim, J. J, Park, E. K. and Kim, D. H. (2004). Metabolic activities of ginsenoside Rb1, baicalin, glycyrrhizin and geniposide to their bioactive compounds by human intestinal microflora. Biol. Pharm. Bull. 27, 1580-1583 https://doi.org/10.1248/bpb.27.1580
  28. Zhu, Y. P. (1998). Chinese Materia Medica. Harwood Academic Publichers, Australia. pp.127-135

Cited by

  1. Degradation Kinetics of 6‴-p-Coumaroylspinosin and Identification of Its Metabolites by Rat Intestinal Flora vol.65, pp.22, 2017, https://doi.org/10.1021/acs.jafc.7b01486
  2. In vitro human fecal microbial metabolism of Forsythoside A and biological activities of its metabolites vol.99, 2014, https://doi.org/10.1016/j.fitote.2014.09.018
  3. Simulated gastrointestinal tract metabolism and pharmacological activities of water extract of Scutellaria baicalensis roots vol.152, pp.1, 2014, https://doi.org/10.1016/j.jep.2013.12.056
  4. Intestinal bacterial metabolism and anti-complement activities of three major components of the seeds of Entada phaseoloides vol.69, pp.2, 2015, https://doi.org/10.1007/s11418-014-0874-4
  5. distribution between Kuqin and Ziqin, two commercial specifications of Scutellaria Radix vol.7, pp.86, 2017, https://doi.org/10.1039/C7RA10705F
  6. -Glucuronidase Activity and Biologically Active Flavones-Aglycone Contents in Hairy Roots of Baikal Skullcap vol.15, pp.2, 2018, https://doi.org/10.1002/cbdv.201700409
  7. Bioconversion of Flavones During Fermentation in Milk Containing Scutellaria baicalensis Extract by Lactobacillus brevis vol.23, pp.10, 2009, https://doi.org/10.4014/jmb.1305.05001
  8. Effects of Intestinal Microecology on Metabolism and Pharmacokinetics of Oral Wogonoside and Baicalin vol.12, pp.4, 2009, https://doi.org/10.1177/1934578x1701200412
  9. Effects of dietary supplementation of enzymatic bio-conversion of Scutellaria baicalensis extract as an alternative to antibiotics on the growth performance, nutrient digestibility, fecal microbiota, vol.244, pp.None, 2009, https://doi.org/10.1016/j.livsci.2020.104307