20(S)-ginsenoside Rh2 noncompetitively inhibits P-glycoprotein in vitro and in vivo: A case for herb-drug interactions

Drug Metabolism and Disposition

Volumn 38, Issue 12, 2010, Pages 2179-2187

  Zhang, Jingwei ^a   Zhou, Fang ^a   Wu, Xiaolan ^a   Gu, Yi ^a,b   Ai, Hua ^a   Zheng, Yuanting ^a   Li, Yannan ^a   Zhang, Xiaoxuan ^a   Hao, Gang ^a   Sun, Jianguo ^a   Peng, Ying ^a   Wang, Guangji ^a  

^a CHINA PHARMACEUTICAL UNIVERSITY   (China)

^b Hutchison Medipharma Ltd   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATASE; DIGOXIN; ETOPOSIDE; FEXOFENADINE; GINSENOSIDE RH 2; GLYCOPROTEIN P; RHODAMINE 123; VERAPAMIL;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG ELIMINATION; DRUG HALF LIFE; DRUG TRANSPORT; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME SUBSTRATE; FLUORESCENCE; HERB DRUG INTERACTION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INHIBITION KINETICS; INTESTINE; INTESTINE ABSORPTION; INTESTINE PERFUSION; LONG TERM CARE; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SINGLE DRUG DOSE;

ANIMALS; CACO-2 CELLS; DIGOXIN; ETOPOSIDE; GINSENOSIDES; HERB-DRUG INTERACTIONS; HUMANS; ILEUM; MALE; P-GLYCOPROTEIN; RATS; RATS, SPRAGUE-DAWLEY; RHODAMINE 123; TERFENADINE; VERAPAMIL;

RATTUS;

EID: 78649580065     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.110.034793     Document Type: Article

References (41)

1. Bai J, Lai L, Yeo HC, Goh BC, and Tan TM (2004) Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol 36:247-257.
2. Bardelmeijer HA, Beijnen JH, Brouwer KR, Rosing H, Nooijen WJ, Schellens JH, and van Tellingen O (2000) Increased oral bioavailability of paclitaxel by GF120918 in mice through selective modulation of P-glycoprotein. Clin Cancer Res 6:4416-4421.
3. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248-254.
4. Chan E, Tan M, Xin J, Sudarsanam S, and Johnson DE (2010) Interactions between traditional Chinese medicines and Western therapeutics. Curr Opin Drug Discov Devel 13:50-65.
5. Chang C, Bahadduri PM, Polli JE, Swaan PW, and Ekins S (2006) Rapid identification of P-glycoprotein substrates and inhibitors. Drug Metab Dispos 34:1976-1984.
6. Dantzig AH, Shepard RL, Cao J, Law KL, Ehlhardt WJ, Baughman TM, Bumol TF, and Starling JJ (1996) Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res 56:4171-4179.
7. Fei XF, Wang BX, Tashiro S, Li TJ, Ma JS, and Ikejima T (2002) Apoptotic effects of ginsenoside Rh2 on human malignant melanoma A375-S2 cells. Acta Pharmacol Sin 23:315-322. (Pubitemid 34266588)
8. Fu LW, Zhang YM, Liang YJ, Yang XP, and Pan QC (2002) The multidrug resistance of tumour cells was reversed by tetrandrine in vitro and in xenografts derived from human breast adenocarcinoma MCF-7/adr cells. Eur J Cancer 38:418-426.
9. Gu Y, Wang GJ, Sun JG, Jia YW, Wang W, Xu MJ, Lv T, Zheng YT, and Sai Y (2009) Pharmacokinetic characterization of ginsenoside Rh2, an anticancer nutrient from ginseng, in rats and dogs. Food Chem Toxicol 47:2257-2268.
10. Gu Y, Wang GJ, Sun JG, Jia YW, Xie HT, and Wang W (2006) Quantitative determination of ginsenoside Rh2 in rat biosamples by liquid chromatography electrospray ionization mass spectrometry. Anal Bioanal Chem 386:2043-2053.
11. Gu Y, Wang GJ, Wu XL, Zheng YT, Zhang JW, Ai H, Sun JG, and Jia YW (2010) Intestinal absorption mechanisms of ginsenoside Rh2: stereoselectivity and involvement of ABC transporters. Xenobiotica doi:10.3109/00498254.2010.500744.
12. Hasegawa H, Sung JH, Matsumiya S, Uchiyama M, Inouye Y, Kasai R, and Yamasaki K (1995) Reversal of daunomycin and vinblastine resistance in multidrug-resistant P388 leukemia in vitro through enhanced cytotoxicity by triterpenoids. Planta Med 61:409-413.
13. Hou XL, Takahashi K, Tanaka K, Tougou K, Qiu F, Komatsu K, Takahashi K, and Azuma J (2008) Curcuma drugs and curcumin regulate the expression and function of P-gp in Caco-2 cells in completely opposite ways. Int J Pharm 358:224-229.
14. Jia WW, Bu X, Philips D, Yan H, Liu G, Chen X, Bush JA, and Li G (2004) Rh2, a compound extracted from ginseng, hypersensitizes multidrug-resistant tumor cells to chemotherapy. Can J Physiol Pharmacol 82:431-437.
15. Kikuchi Y, Sasa H, Kita T, Hirata J, Tode T, and Nagata I (1991) Inhibition of human ovarian cancer cell proliferation in vitro by ginsenoside Rh2 and adjuvant effects to cisplatin in vivo. Anticancer Drugs 2:63-67.
16. Kim HS, Lee EH, Ko SR, Choi KJ, Park JH, and Im DS (2004) Effects of ginsenosides Rg3 and Rh2 on the proliferation of prostate cancer cells. Arch Pharm Res 27:429-435.
17. Kitagawa I, Yoshikawa M, Yoshihara M, Hayashi T, and Taniyama T (1983) Chemical studies of crude drugs (1). Constituents of Ginseng radix rubra. Yakugaku Zasshi 103:612-622.
18. Kwak JO, Lee SH, Lee GS, Kim MS, Ahn YG, Lee JH, Kim SW, Kim KH, and Lee MG (2010) Selective inhibition of MDR1 (ABCB1) by HM30181 increases oral bioavailability and therapeutic efficacy of paclitaxel. Eur J Pharmacol 627:92-98.
19. Lancet JE, Baer MR, Duran GE, List AF, Fielding R, Marcelletti JF, Multani PS, and Sikic BI (2009) A phase I trial of continuous infusion of the multidrug resistance inhibitor zosuquidar with daunorubicin and cytarabine in acute myeloid leukemia. Leuk Res 33:1055-1061.
20. Liu H, Yang J, Du F, Gao X, Ma X, Huang Y, Xu F, Niu W, Wang F, Mao Y, et al. (2009) Absorption and disposition of ginsenosides after oral administration of Panax notoginseng extract to rats. Drug Metab Dispos 37:2290-2298.
21. Maki N, Hafkemeyer P, and Dey S (2003) Allosteric modulation of human P-glycoprotein. Inhibition of transport by preventing substrate translocation and dissociation. J Biol Chem 278:18132-18139.
22. Maki N, Moitra K, Ghosh P, and Dey S (2006) Allosteric modulation bypasses the requirement for ATP hydrolysis in regenerating low affinity transition state conformation of human P-glycoprotein. J Biol Chem 281:10769-10777.
23. Marchetti S, Mazzanti R, Beijnen JH, and Schellens JH (2007) Concise review: Clinical relevance of drug-drug and herb-drug interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein). Oncologist 12:927-941.
24. Mechetner EB, Schott B, Morse BS, Stein WD, Druley T, Davis KA, Tsuruo T, and Roninson IB (1997) P-glycoprotein function involves conformational transitions detectable by differential immunoreactivity. Proc Natl Acad Sci USA 94:12908-12913.
25. Mistry P, Stewart AJ, Dangerfield W, Okiji S, Liddle C, Bootle D, Plumb JA, Templeton D, and Charlton P (2001) In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576. Cancer Res 61:749-758.
26. Nishimura T, Kato Y, Amano N, Ono M, Kubo Y, Kimura Y, Fujita H, and Tsuji A (2008) Species difference in intestinal absorption mechanism of etoposide and digoxin between cynomolgus monkey and rat. Pharm Res 25:2467-2476.
27. Ozvegy C, Litman T, Szakács G, Nagy Z, Bates S, Váradi A, and Sarkadi B (2001) Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem Biophys Res Commun 285:111-117.
28. Petri N, Tannergren C, Rungstad D, and Lennernäs H (2004) Transport characteristics of fexofenadine in the Caco-2 cell model. Pharm Res 21:1398-1404.
29. Pires MM, Hrycyna CA, and Chmielewski J (2006) Bivalent probes of the human multidrug transporter P-glycoprotein. Biochemistry 45:11695-11702.
30. Qiu J (2007) 'Back to the future' for Chinese herbal medicines. Nat Rev Drug Discov 6:506-507.
31. Rengelshausen J, Banfield M, Riedel KD, Burhenne J, Weiss J, Thomsen T, Walter-Sack I, Haefeli WE, and Mikus G (2005) Opposite effects of short-term and long-term St John's wort intake on voriconazole pharmacokinetics. Clin Pharmacol Ther 78:25-33.
32. Sun M, Xu X, Lu Q, Pan Q, and Hu X (2007) Schisandrin B: a dual inhibitor of P-glycoprotein and multidrug resistance-associated protein 1. Cancer Lett 246:300-307.
33. Takeuchi T, Yoshitomi S, Higuchi T, Ikemoto K, Niwa S, Ebihara T, Katoh M, Yokoi T, and Asahi S (2006) Establishment and characterization of the transformants stably-expressing MDR1 derived from various animal species in LLC-PK1. Pharm Res 23:1460-1472.
34. Thomas H and Coley HM (2003) Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein. Cancer Control 10:159-165.
35. Ujie K, Oda M, Kobayashi M, and Saitoh H (2008) Relative contribution of absorptive and secretory transporters to the intestinal absorption of fexofenadine in rats. Int J Pharm 361:7-11.
36. Wang X and Morris ME (2007) Effects of the flavonoid chrysin on nitrofurantoin pharmacokinetics in rats: potential involvement of ABCG2. Drug Metab Dispos 35:268-274.
37. Wang Z, Zheng Q, Liu K, Li G, and Zheng R (2006) Ginsenoside Rh2 enhances antitumour activity and decreases genotoxic effect of cyclophosphamide. Basic Clin Pharmacol Toxicol 98:411-415.
38. Xie HT, Wang GJ, Chen M, Jiang XL, Li H, Lv H, Huang CR, Wang R, and Roberts M (2005) Uptake and metabolism of ginsenoside Rh2 and its aglycon protopanaxadiol by Caco-2 cells. Biol Pharm Bull 28:383-386.
39. Xie X, Eberding A, Madera C, Fazli L, Jia W, Goldenberg L, Gleave M, and Guns ES (2006) Rh2 synergistically enhances paclitaxel or mitoxantrone in prostate cancer models. J Urol 175:1926-1931.
40. Xu WL, Shen HL, Ao ZF, Chen BA, Xia W, Gao F, and Zhang YN (2006) Combination of tetrandrine as a potential-reversing agent with daunorubicin, etoposide and cytarabine for the treatment of refractory and relapsed acute myelogenous leukemia. Leuk Res 30:407-413.
41. Zhao Y, Bu L, Yan H, and Jia W (2009) 20S-protopanaxadiol inhibits P-glycoprotein in multidrug resistant cancer cells. Planta Med 75:1124-1128.