Inchinkoto, a herbal medicine, and its ingredients dually exert Mrp2/MRP2-mediated choleresis and Nrf2-mediated antioxidative action in rat livers

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 292, Issue 5, 2007, Pages

  Okada, Kosuke ^a   Shoda, Junichi ^a   Kano, Masahito ^a   Suzuki, Sachiko ^b   Ohtake, Nobuhiro ^b   Yamamoto, Masahiro ^b   Takahashi, Hiroshi ^a   Utsunomiya, Hirotoshi ^c   Oda, Koji ^d   Sato, Kimi ^a   Watanabe, Ayaka ^a   Ishii, Tetsuro ^a   Itoh, Ken ^a   Yamamoto, Masayuki ^a   Yokoi, Tsuyoshi ^e   Yoshizato, Katsutoshi ^f,g   Sugiyama, Yuichi ^h   Suzuki, Hiroshi ⁱ  

^a UNIVERSITY OF TSUKUBA   (Japan)

^b TSUMURA AND CO   (Japan)

^c WAKAYAMA MEDICAL UNIVERSITY   (Japan)

^d NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^e KANAZAWA UNIVERSITY   (Japan)

^f HIROSHIMA UNIVERSITY   (Japan)

^g HIROSHIMA UNIVERSITY   (Japan)

^h UNIVERSITY OF TOKYO   (Japan)

ⁱ UNIVERSITY OF TOKYO HOSPITAL   (Japan)

Author keywords

Bilirubin; Chimeric mice with humanized liver; Gluthathione; Heme oxygenase 1; Multidrug resistance associated proteins; Nuclear factor E2 related factor

Indexed keywords

BILIRUBIN; GENIPIN; GLUTATHIONE; HEME OXYGENASE 1; HERBACEOUS AGENT; INCHINKO TO; MESSENGER RNA; MULTIDRUG RESISTANCE PROTEIN 2; TRANSCRIPTION FACTOR NRF2; UNCLASSIFIED DRUG; ABC TRANSPORTER; ABCC2 PROTEIN, RAT; ANTIOXIDANT; CHOLAGOGUE; HEME OXYGENASE; HMOX1 PROTEIN, RAT; INCHINKO-TO; IRIDOID; NFE2L2 PROTEIN, RAT; ORGANIC ANION TRANSPORTER;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIOXIDANT ACTIVITY; ARTICLE; BILE FLOW; BILIARY EXCRETION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; DRUG POTENCY; EMBRYO; HERBAL MEDICINE; INTRAHEPATIC BILE DUCT; KIDNEY PROXIMAL TUBULE; LIVER; LIVER CELL; LIVER LEVEL; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN SYNTHESIS; RAT; ANIMAL; BILE; BIOSYNTHESIS; CELL CULTURE; KIDNEY; METABOLISM; PHYSIOLOGY; SECRETION; SPRAGUE DAWLEY RAT;

ANIMALS; ANTIOXIDANTS; ATP-BINDING CASSETTE TRANSPORTERS; BILE; CELLS, CULTURED; CHOLAGOGUES AND CHOLERETICS; DRUGS, CHINESE HERBAL; GLUTATHIONE; HEME OXYGENASE (DECYCLIZING); IRIDOIDS; KIDNEY; LIVER; MALE; MICE; NF-E2-RELATED FACTOR 2; ORGANIC ANION TRANSPORTERS; RATS; RATS, SPRAGUE-DAWLEY;

EID: 34347377398     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00302.2006     Document Type: Article

References (59)

1. Aburada M, Sasaki H, Harada M. Pharmacological studies of Gardeniae fructus. II. Contribution of the constituent crude drugs to choleretic activity of Inchin-ko-to in rats. Yakugaku Zasshi 96: 147-153, 1976.
2. Akao T, Kobayashi K, Aburada M. Enzymic studies on the animal and intestinal bacterial metabolism of geniposide. Biol Pharm Bull 17: 1573-1576, 1994.
3. Amersi F, Buelow R, Kato H, Ke B, Coito AJ, Shen XD, Zhao D, Zaky J, Melinek J, Lassman CR, Kolls JK, Alam J, Ritter T, Volk HD, Farmer DG, Ghobrial RM, Busuttil RW, Kupiec-Weglinski JW. Upregulation of heme oxygenase-1 protects genetically fat zucker rat livers from ischemia/reperfusion injury. J Clin Invest 104: 1631-1639, 1999.
4. Anwer MS. Cellular regulation of hepatic bile acid transport in health and cholestasis. Hepatology 39: 581-590, 2004.
5. Beaver JP, Waring P. A decrease in intracellular glutathione concentration precedes the onset of apoptosis in murine thymocytes. Eur J Cell Biol 68: 47-54, 1995.
6. Belinsky MG, Dawson PA, Shchaveleva I, Bain LJ, Wang R, Ling V, Chen ZS, Grinberg A, Westphal H, Klein-Szanto A, Lerro A, Kruh GD. Analysis of the in vivo functions of Mrp3. Mol Pharmacol 68: 160-168, 2005.
7. Bolder U, Ton-Nu HT, Schteingart CD, Frick E, Hofmann AF. Hepatocyte transport of bile acids and organic anions in endotoxemic rats: impaired uptake and secretion. Gastroenterology 112: 214-225, 1997.
8. Bossard R, Strieger B, O'Neill B, Fricker G, Meier PJ. Ethinylestradiol treatment induces multiple canalicular membrane transport alterations in rat liver. J Clin Invest 91: 2714-2720, 1993.
9. Bossard R, Strieger B, O'Neill B, Fricker G, Meier PJ. Ethinylestradiol treatment induces multiple canalicular membrane transport alterations in rat liver. J Clin Invest 91: 2714-2720, 1993.
10. Buchler M, Konig J, Brom M, Kartenbeck J, Spring H, Horie T, Keppler D. cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic rats. J Biol Chem 271: 15091-15098, 1996.
11. Cao J, Stieger B, Meier PJ, Vore M. Expression of rat hepatic multidrug resistance-associated proteins and organic anion transporters in pregnancy. Am J Physiol Gastrointest Liver Physiol 283: G757-G766, 2002.
12. Chiang JY. Bile acid regulation of hepatic physiology. III. Bile acids and nuclear receptors. Am J Physiol Gastrointest Liver Physiol 284: G349-G356, 2003.
13. Chu CY, Tseng TH, Hwang JM, Chou FP, Wang CJ. Protective effects of capillarisin on tert-butylhydroperoxide-induced oxidative damage in rat primary hepatocytes. Arch Toxicol 73: 263-268, 1999.
14. Fickert P, Zollner G, Fuchsbichler A, Stumtner C, Pojer C, Zwnz R, Lammert F, Stieger B, Meier PJ, Zatloukal H, Trauner M. Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. Gastroenterology 121: 170-183, 2001.
15. Goldfarb S, Singer EJ, Popper H. Experimental cholangitis due to alpha-naphthylisothiocyanate (ANIT). Am J Pathol 40: 685-698, 1962.
16. Hayashi A, Suzuki H, Itoh K, Yamamoto M, Sugiyama Y. Transcriptional factor Nrf2 is required for the constitutive and inducible expression of multidrug resistance-associated protein 1 in mouse embryo fibroblasts. Biochem Biophys Res Commun 310: 824-829, 2003.
17. Hayes JD, McMahon M. Molecular basis for the combination of the antioxidant responsive element to cancer chemoprevention. Cancer Lett 174: 103-113, 2001.
18. Hirohashi T, Suzuki H, Ito K, Ogawa K, Kume K, Shimizu T, Sugiyama Y. Hepatic expression of multidrug resistance-associated protein-like proteins maintained in Esai hyperbilirubinemic rats. Mol Pharmacol 53: 1068-1075, 1998.
19. Huang W, Zhang J, Moore DD. A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR. J Clin Invest 113: 137-143, 2004.
20. Ishii T, Itoh K, Takahashi S, Sato H, Yanagawa T, Katoh Y, Bannnai S, Yamamoto M. Transcriptional factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J Biol Chem 275: 16023-16029, 2000.
21. Ito K, Suzuki H, Hirohashi T, Kume K, Shimizu T, Sugiyama Y. Functional analysis of a canalicular multispecific organic anion transporter cloned from rat liver. J Biol Chem 273: 1684-1688, 1998.
22. Itoh K, Chiba S, Takahashi T, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi K, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236: 313-322, 1997.
23. Ji B, Ito K, Sekine S, Tajima A, Horie T. Ethacrynic-acid-induced glutathione depletion and oxidative stress in normal and Mrp2-deficient rat liver. Free Radic Biol Med 37: 1718-1729, 2004.
24. Kanz MF, Dugas TR, Liu H, Santa Cruz V. Glutathione depletion exacerbates methylenedianiline toxicity to biliary epithelial cells and hepatocytes in rats. Toxicol Sci 74: 447-456, 2003.
25. Karpen SJ. Nuclear receptor regulation of hepatic function. J Hepatol 36: 832-850, 2002.
26. Keppler D, König J. Expression and localization of the conjugate export pump encoded by the MRP2 (cMRP/cMOAT) gene in liver. FASEB J 11: 509-516, 1997.
27. Konig J, Nies AT, Cui Y, Leier I, Keppler D. Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance. Biochim Biophys Acta 1461: 377-394, 1999.
28. Kool M, van der Linden M, de Hass M, Scheffer GL, de Vree JML, Smith AJ, Jansen G, Peters GJ, Ponne N, Scheper RJ, Oude Elferink RPJ, Bass F, Boast P. MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc Natl Acad Sci USA 96: 6914-6919, 1999.
29. Kullak-Ublick GA, Beuers U, Paumgartner G. Hepatobiliary transport. J Hepatol 32: 3-18, 2000.
30. Lu SC, Kuhlenkamp J, Garcia-Ruiz C, Kaplowitz N. Hormone-mediated down-regulation of hepatic glutathione synthesis in the rat. J Clin Invest 88: 260-269, 1991.
31. Madon J, Eckhardt U, Gerloff T, Stieger B, Meier PJ. Functional expression of the rat liver canalicular isoform of the multidrug resistance-associated protein. FEBS Lett 406: 75-78, 1997.
32. Maher JM, Cheng X, Slitt AL, Dieter MZ, Klaassen CD. Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver. Drug Metab Dispos 33: 956-962, 2005.
33. Maines MD. Heme oxygenase: multifunction, multiplicity, regulatory mechanisms and clinical application. FASEB J 2: 2557-2568, 1998.
34. Mashige F, Tanaka N, Maki A, Kamei S, Yamanaka M. Direct spectrophotometry of total bile acids in serum. Clin Chim Acta 27: 1352-1356, 1981.
35. Mennone A, Soroka CJ, Cai SY, Harry K, Adachi M, Hagey L, Schuetz JD, Boyer JL. Mrp4-/- mice have an impaired cytoprotective response in obstructive cholestasis. Hepatology 43: 1013-1021, 2006.
36. Ogawa K, Suzuki H, Hirohashi T, Ishikawa T, Meier PJ, Hirose K, Akizawa T, Yoshioka M, Sugiyama Y. Characterization of inducible nature of MRP3 in rat liver. Am J Physiol Gastrointest Liver Physiol 278: G438-G446, 2000.
37. Paulusma CC, Bosma PJ, Zaman GJ, Bakker CT, Otter M, Scheffer GL, Scheper RJ, Borst P, and Oude Elferink RP. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science 271: 1126-1128, 1996.
38. Payen L, Sparfel L, Courtois A, Vernhet L, Guillouzo A, Fardel O. The drug efflux pump MRP2: regulation of expression in physiopathological situations and by endogenous and exogeneous compounds. Cell Biol Toxicol 18: 221-233, 2002.
39. Sasaki H, Sato H, Kuriyama K, Sayo K, Maebara K, Wang H, Tamba M, Itoh K, Yamamoto M, Bannnai S. Electrophilic responsible element-mediated induction of the cystine/glutamate exchanger transporter gene expression. J Biol Chem 277: 44765-44771, 2002.
40. Sass G, Soares MCP, Yamashita K, Seyfried S, Zimmermann WH, Eschenhagen T, Kaczmarek E, Ritter T, Volk HD, Tiegs G. Heme oxygenase-1 and its reaction product, carbon monoxide, prevent inflammation-related apoptotic liver damage in mice. Hepatology 38: 909-918, 2003.
41. Shoda J, Inada Y, Tsuji A, Kusama H, Ueda T, Ikegami T, Suzuki H, Sugiyama Y, Cohen DE, Tanaka N. Bezafibrate stimulates canalicular localization of NBD-labeled PC in HepG2 cells by PPARalpha-mediated redistribution of ABCB4. J Lipid Res 45: 1813-1825, 2004.
42. Shoda J, Kano M, Oda K, Kamiya K, Nimura Y, Suzuki H, Sugiyama Y, Miyazaki H, Todoroki T, Stengelin S, Kramer W, Matsuzaki Y, Tanaka N. 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: 3368-3378, 2001.
43. Shoda J, Miura T, Utsunomiya H, Oda K, Yamamoto M, Kano M, Ikegami T, Tanaka N, Akita H, Ito K, Suzuki H, Sugiyama Y. Genipin enhances Mrp2 (Abcc2)-mediated bile formation and organic anion transport in rat liver. Hepatology 39: 167-178, 2004.
44. Soroka CJ, Lee JM, Azzaroli F, Boyer JL. Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver. Hepatology 33: 783-791, 2001.
45. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN. Bilirubin is an antioxidant of possible physiological importance. Science 235: 1043-1046, 1987.
46. Suematsu M, Kashiwagi S, Sano T, Goda N, Shinoda Y, Ishimura Y. Carbon monoxide as an endogenous modulator of hepatic vascular perfusion. Biochem Biophys Res Commun 205: 1333-1337, 1994.
47. Takeda S, Endo T, Aburada M. Pharmacological studies on iridoid compounds. III. The choleretic mechanism of iridoid compounds. J Pharmacobio-Dyn 4: 612-623, 1981.
48. Takeda S, Iizuka A, Funo S, Sudo K, Kikuchi N, Yoshida C, Aburada M, Hosoya E. Effect of Chinese prescription "Inchin-ko-to" on experimental hepatobiliary injury induced by α-naphthylisothiocyanate. Wakan-Yaku 1: 230-234, 1984.
49. Tateno C, Yoshizane Y, Saito N, Kataoka M, Tachibana A, Soeno Y, Asahina K, Hino H, Asahara T, Yokoi T, Furukawa T, Yoshizato K. Near completely humanized liver in mice shows human-type metabolic responses to drugs. Am J Pathol 165: 901-912, 2004.
50. Trauner M, Boyer JM. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 83: 633-671, 2003.
51. Trauner M, Arrese M, Soroka CJ, Ananthanarayanan M, Koeppel TA, Schlosser SF, Suchy FJ, Keppler D, Boyer JL. The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis. Gastroenterology 113: 255-264, 1997.
52. Trauner M, Meier PJ, Boyer JL. Molecular pathogenesis of cholestasis. N Engl J Med 339: 1217-1227, 1998.
53. Vina J, Hems R, Krebs HA. Reaction of formiminoglutamate with liver glutamate dehydrogenase. Biochem J 170: 711-713, 1978.
54. Wagner M, Fickert P, Zollner G, Fuchsbichler A, Silbert D, Tsybrovskyy O, Zatloukal K, Guo GL, Schetz JD, Gonzalez FJ, Marschall HU, Denk H, Trauner M. Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice. Gastroenterology 125: 825-839, 2003.
55. Yamada T, Arai T, Iwahashi N, Kamiya J, Nagino M, Oda K, Shoda J, Suzuki H, Sugiyama Y, Nimura Y. Impaired expression of hepatic multidrug resistance protein 2 is associated with posthepatectomy liver failure in patients with biliary tract carcinoma. Langenbeck Arch Surg 390: 421-429, 2005.
56. Yamamoto M, Shoda J. Inchinko-to. Drugs Future 30: 1092-1101, 2005.
57. Yamamoto M, Miura N, Ohtake N, Amagaya S, Ishige A, Sasaki H, Komatsu Y, Fukuda K, Ito T, Terasawa K. Genipin, a metabolite derived from the herbal medicine Inchin-ko-to, and suppression of fas-induced lethal liver apoptosis in mice. Gastroenterology 118: 380-389, 2001.
58. Yamamoto M, Ogawa K, Morita M, Fukuda K, Komatsu Y. The herbal medicine Inchin-ko-to inhibits liver cell apoptosis induced by transforming growth factor beta 1. Hepatology 23: 52-59, 1996.
59. Zelcer N, van de Wetering K, de Waart R, Scheffer GL, Marschall HU, Wielinga PR, Kuil A, Kunne C, Smith A, van der Valk M, Wijinholds J, Oude Elferink R, Borst P. Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides. J Hepatol 44: 768-775, 2006.