Advertisement

Inchinkoto and Jaundice

  • Junichi ShodaEmail author
  • Eiji Warabi
  • Kosuke Okada
  • Masahiro Yamamoto
Protocol
Part of the Methods in Pharmacology and Toxicology book series (MIPT)

Abstract

Patients suffering from cholestasis and jaundice are frequently encountered in daily clinical practice. Cholestasis is a pathological condition characterized by impaired bile formation and secretion in livers. The accompanying oxidative stress may damage hepatocytes and thereby result in severe jaundice (hyperbilirubinemia), leading to liver fibrosis. Kampo formulation inchinkoto (IKCT) has been recognized as a “magic bullet” for the treatment of jaundice. Although the potent hepatoprotective and choleretic actions and main active ingredients of IKCT have long been known, the recent advances in research of bile formation and hepatic transporters have opened a road to the understanding of the action mechanism. In this chapter, the molecular mechanism of the clinically useful actions induced by ICKT is described in detail.

Key words

Jaundice Cholestasis Bilirubin Inchikoto Genipin Abcc2 (Mrp2) Nrf2 

References

  1. 1.
    Kullak-Ublick GA, Beuers U, Paumgartner G (2000) Hepatobiliary transport. J Hepatol 32:3–18CrossRefPubMedGoogle Scholar
  2. 2.
    Trauner M, Meier PJ, Boyer JL (1998) Molecular pathogenesis of cholestasis. N Engl J Med 339:1217–1227CrossRefPubMedGoogle Scholar
  3. 3.
    Shoda J, Kano M, Oda K et al (2001) The expression levels of plasma membrane transporters in the cholestatic liver of patients undergoing biliary drainage and their association with the impairment of biliary secretory function. Am J Gastroenterol 96:3368–3378CrossRefPubMedGoogle Scholar
  4. 4.
    Aburada M, Sasaki H, Harada M (1976) Pharmacological studies of gardeniae fructus. II. Contribution of the constituent crude drugs to choleretic activity of Inchin-ko-to in rats [English abstract]. Yakugaku Zasshi 96:147–153PubMedGoogle Scholar
  5. 5.
    Shoda J, Miura T, Yamamoto M et al (2004) Genipin, an active metabplite of a herbalmedicine Inchinko-To, enhances multidrug resistance-associated protein 2-mediated bile formation in rats. Hepatology 39:167–178CrossRefPubMedGoogle Scholar
  6. 6.
    Anwer MS (2004) Cellular regulation of hepatic bile acid transport in health and cholestasis. Hepatology 39:581–590CrossRefPubMedGoogle Scholar
  7. 7.
    Beuers U, Bilzer M, Chittattu A et al (2001) Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic liver. Hepatology 33:1206–1216CrossRefPubMedGoogle Scholar
  8. 8.
    Roelofsen H, Soroka CJ, Keppler D et al (1998) Cyclic AMP stimulates sorting of the canalicular organic anion transporter (Mrp2/cMOAT) to the apical domain in hepatocyte couplets. J Cell Sci 111:1137–1145PubMedGoogle Scholar
  9. 9.
    Okada K, Shoda J, Kano M et al (2007) Inchinkoto, a herbal medicine, and its ingredients dually exert Mrp2/MRP2-mediated choleresis and Nrf2-mediated antioxidative action in rat livers. Am J Physiol 292:G1450–G1463Google Scholar
  10. 10.
    Takeda S, Endo T, Aburada M (1981) Pharmacological studies on iridoid compounds. III. The choleretic mechanism of iridoid compounds. J Pharmacobiodyn 4:612–623CrossRefPubMedGoogle Scholar
  11. 11.
    Huang W, Zhang J, Moore DD (2004) A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR. J Clin Invest 113:137–143CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Komiya T, Tsukui M, Oshio H (1976) Studies on “Inchinko”. I. Capillarisin, a new choleretic substance [abstract in English]. Yakugaku Zasshi 96:841–854PubMedGoogle Scholar
  13. 13.
    Kagawa K, Okuno I, Noro Y (1984) Colorimetric determination of capillarisin. Shoyakugaku Zasshi 38:133–137Google Scholar
  14. 14.
    Okuno I, Kagawa K, Noro Y et al (1983) Pharmacological studies on the crude drug “Inchinko” in Japan (VI). Seasonal variation in chemical constituents of Artemisia capillaris THUNB. Shoyakugaku Zasshi 37:199–203Google Scholar
  15. 15.
    Akahori A, Kagawa K, Okuno I (1978) Determination of scoparone, capillarin and capllin in the crude drug “Inchinko” [abstract in English]. Shoyakugaku Zasshi 32:177–184Google Scholar
  16. 16.
    Wang X, Saito K, Kano Y et al (1993) On the evaluation of the prepa- ration of Chinese medicinal prescriptions (VII). HPLC analysis of the components in “Inchinko-to” and “Inchin-gorei-san”. Shoyakugaku Zasshi 47:243–248Google Scholar
  17. 17.
    Yamahara J, Matsuda H, Sawada T et al (1982) Biologically active principles of crude drugs. Pharmacological evaluation of Artemisiae capillaris FLOS [abstract in English]. Yakugaku Zasshi 102:285–291PubMedGoogle Scholar
  18. 18.
    Okuno I, Uchida K, Nakamura M et al (1988) Studies on choleretic constituents in Artemisia capillaris THUNB. Chem Pharm Bull (Tokyo) 36:769–775CrossRefGoogle Scholar
  19. 19.
    Kitagawa I, Fukuda Y, Yoshihara M et al (1983) Capillartemisin A and B, two new choleretic prin- ciples from Artemisiae capillaris herba. Chem Pharm Bull (Tokyo) 31:352–355CrossRefGoogle Scholar
  20. 20.
    Arab JP, Ramiez C, Munoz P et al (2009) Effects of Japanese herbal medicine Inchin-ko-to on endotoxin-induced cholestasis in the rat. Ann Hepatol 8:228–233PubMedGoogle Scholar
  21. 21.
    Weber-Mzell D, Zaupa P, Petnehazy T et al (2006) The role of nuclear factor-kappa B in bacterial translocation in cholestatic rats. Pediatr Surg Int 22:43–49CrossRefPubMedGoogle Scholar
  22. 22.
    Arai M, Yokosuka O, Fukai K et al (2004) A case of severe acute hepatitis of unknown etiology treated with the Chinese herbal medicine Inchinko-to. Hepatol Res 28:161–165CrossRefPubMedGoogle Scholar
  23. 23.
    Ohwada S, Kobayashi I, Harasawa N et al (2009) Severe acute cholestatic hepatitis of unknown etiology successfully treated with the Chinese herbal medicine Inchinko-to (TJ-135). W J Gastroenterol 15:2927–2929CrossRefGoogle Scholar
  24. 24.
    Ichikawa T, Sato H, Kaira K et al (2008) Prolonged intrahepatic cholestasis after exposure to loxoprofen. Clin Ther 30:2402–2406CrossRefPubMedGoogle Scholar
  25. 25.
    Onji M, Kikuchi T, Michikata K et al (1990) Combined use of ursodeoxycholic acid and Inchin-ko-to in jaundiced patients with primary biliary cirrhosis. J Med Pharm Soc Wakan-Yaku 7:161–167Google Scholar
  26. 26.
    Kobayashi H, Horikoshi K, Yamataka A et al (2001) Beneficial effect of a traditional herbal medicine (Inchin-ko-to) in postoperative biliary atresia patients. Pediatr Surg Int 17:386–389CrossRefPubMedGoogle Scholar
  27. 27.
    Kaiho T, Tsuchiya S, Yanagisawa S et al (2008) Effect of the herbal medicine Inchin-Ko-To for serum bilirubin in hepatectomized patients. Hepatogastroenterology 55:150–154PubMedGoogle Scholar
  28. 28.
    Watanabe S, Yokoyama Y, Oda K et al (2009) Choleretic effect of Inchinkoto, a herbal medicine, on the livers of patients with biliary obstruction due to bile duct carcinoma: a randomized controlled study. Hepatol Res 39:247–255CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Junichi Shoda
    • 1
    Email author
  • Eiji Warabi
    • 2
  • Kosuke Okada
    • 1
  • Masahiro Yamamoto
    • 3
  1. 1.Division of Medical Sciences, Institute of Clinical MedicineUniversity of TsukubaTsukuba, IbarakiJapan
  2. 2.Division of Biomedical Sciences, Faculty of MedicineUniversity of TsukubaTsukuba, IbarakiJapan
  3. 3.Kampo Scientific Strategies Division, Tsumura & Co.Tsumura Research LaboratoriesIbarakiJapan

Personalised recommendations