Intestinal absorption of aloin, aloe-emodin, and aloesin; A comparative study using two in vitro absorption models

  • Park, Mi-Young (Department of Food and Nutrition, Sookmyung Women's University) ;
  • Kwon, Hoon-Jeong (Department of Food and Nutrition, Seoul National University) ;
  • Sung, Mi-Kyung (Department of Food and Nutrition, Sookmyung Women's University)
  • Published : 2009.03.31

Abstract

Aloe products are one of the top selling health-functional foods in Korea, however the adequate level of intake to achieve desirable effects are not well understood. The objective of this study was to determine the intestinal uptake and metabolism of physiologically active aloe components using in vitro intestinal absorption model. The Caco-2 cell monolayer and the everted gut sac were incubated with $5-50{\mu}M$ of aloin, aloe-emodin, and aloesin. The basolateral appearance of test compounds and their glucuronosyl or sulfated forms were quantified using HPLC. The % absorption of aloin, aloe-emodin, and aloesin was ranged from 5.51% to 6.60%, 6.60% to 11.32%, and 7.61% to 13.64%, respectively. Up to 18.15%, 18.18%, and 38.86% of aloin, aloe-emodin, and aloesin, respectively, was absorbed as glucuronidated or sulfated form. These results suggest that a significant amount is transformed during absorption. The absorption rate of test compounds except aloesin was similar in two models; more aloesin was absorbed in the everted gut sac than in the Caco-2 monolayer. These results provide information to establish adequate intake level of aloe supplements to maintain effective plasma level.

Keywords

References

  1. Alves DS, Perez-Fons L, Estepa A & Micol V (2004). Membranerelated effects underlying the biological activity of the anthraquinones emodin and barbaloin. Biochem Pharmacol 68:549-561 https://doi.org/10.1016/j.bcp.2004.04.012
  2. Azuma K, Ippoushi K, Ito H, Higashio H & Terao J (2002). Combination of lipids and emulsifiers enhances the absorption of orally administered quercetin in rats. J Agric Food Chem 50:1706-1712 https://doi.org/10.1021/jf0112421
  3. Barthe L, Woodley J & Houin G (1999). Gastrointestinal absorption of drugs: methods and studies. Fundam Clin Pharmacol 13:154-168 https://doi.org/10.1111/j.1472-8206.1999.tb00334.x
  4. Chandan BK, Saxena AK, Shukla S, Sharma N, Gupta DK, Suri KA, Suri J, Bhadauria M & Singh B (2007). Hepatoprotective potential of Aloe barbadensis Mill. against carbon tetrachloride induced hepatotoxicity. J Ethnopharmacol 111:560-566 https://doi.org/10.1016/j.jep.2007.01.008
  5. Davis RH, Donato JJ, Hartman GM & Haas RC (1994). Antiinflammatory and wound healing activity of a growth substance in Aloe vera. J Am Podiatr Med Assoc 84:77-81 https://doi.org/10.7547/87507315-84-2-77
  6. Esmat AY, Tomasetto C & Rio MC (2006). Cytotoxicity of a natural anthraquinone (Aloin) against human breast cancer cell lines with and without ErbB-2: topoisomerase IIalpha coamplification. Cancer Biol Ther 5:97-103 https://doi.org/10.1158/1535-7163.MCT-05-0365
  7. Gee JM, DuPont MS, Rhodes MJ & Johnson IT (1998). Quercetin glucosides interact with the intestinal glucose transport pathway. Free Radic Biol Med 25:19-25 https://doi.org/10.1016/S0891-5849(98)00020-3
  8. Hadjeri M, Barbier M, Ronot X, Mariotte AM, Boumendjel A & Boutonnat J (2003). Modulation of P-glycoprotein-mediated multidrug resistance by flavonoid derivatives and analogues. J Med Chem 46: 2125-2131 https://doi.org/10.1021/jm021099i
  9. Hidalgo IJ, Raub TJ & Borchardt RT (1989). Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 96:736-749 https://doi.org/10.1016/S0016-5085(89)80072-1
  10. Ishii Y, Tanizawa H & Takino Y (1994). Studies of aloe. V. Mechanism of cathartic effect. Biol Pharm Bull 17:651-653 https://doi.org/10.1248/bpb.17.651
  11. Kanai Y, Nakai Y, Nakajima N & Tanayama S (1979). Metabolic disposition of 6-ethyl-3-(1H-tetrazol-5-yl)-chromone, a new antiallergic agent, in the rat, guinea-pig, rabbit, dog and monkey. Xenobiotica 9:33-50 https://doi.org/10.3109/00498257909034702
  12. Keller RP & Neville MC (1986). Determination of total protein in human milk: comparison of methods. Clin Chem 32:120-123
  13. Korkina L, Suprun M, Petrova A, Mikhal'chik E, Luci A & De Luca C (2003). The protective and healing effects of a natural antioxidant formulation based on ubiquinol and aloe vera against dextran sulfate-induced ulcerative colitis in rats. J Am Podiatr Med Assoc 84:77-81 https://doi.org/10.1002/biof.5520180228
  14. Lambert N, Kroon PA, Faulds CB, Plumb GW, McLauchlan WR, Day AJ & Williamson G (1999). Purification of cytosolic beta-glucosidase from pig liver and its reactivity towards flavonoid glycosides. Biochim Biophys Acta 1435:110-116 https://doi.org/10.1016/S0167-4838(99)00213-7
  15. Liu X, Tam VH & Hu M (2007). Disposition of flavonoids via enteric recycling: determination of the UDP-glucuronosyltransferase isoforms responsible for the metabolism of flavonoids in intact Caco-2 TC7 cells using siRNA. Mol Pharm 4:873-882 https://doi.org/10.1021/mp0601190
  16. Maenthaisong R, Chaiyakunapruk N, Niruntraporn S & Kongkaew C (2007). The efficacy of aloe vera used for burn wound healing: a systematic review. Burns 33:713-718 https://doi.org/10.1016/j.burns.2006.10.384
  17. Mailleau C, Capeau J & Brahimi-Horn MC (1998). Interrelationship between the Na+/glucose cotransporter and CFTR in Caco-2 cells: relevance to cystic fibrosis. J Cell Physiol 176:472-481 https://doi.org/10.1002/(SICI)1097-4652(199809)176:3<472::AID-JCP4>3.0.CO;2-L
  18. Maurizis JC, Nicolas C, Verny M, Ollier M, Faurie M, Payard M & Veyre A (1991). Biodistribution and metabolism in rats and mice of bucromarone. Drug Metab Dispos 19:94-99
  19. McCarthy TJ & Haynes LJ (1967). The distribution of alosein in some south African aloe species. Planta Med 15:342-344 https://doi.org/10.1055/s-0028-1099992
  20. Miao H & Yang Z (2000). Regiospecific carbonylative annulation of iodophenol acetates and acetylenes to construct the flavones by a new catalyst of palladium-thiourea-dppp complex. Org Lett 2:1765-1768 https://doi.org/10.1021/ol000087t
  21. Moore Z & Cowman S (2008). A systematic review of wound cleansing for pressure ulcers. J Clin Nurs 17:1963-1972 https://doi.org/10.1111/j.1365-2702.2008.02381.x
  22. Muni IA, Leeling JL, Helms RJ & Johnson N (1978). Antiallergic chromones. I. Disposition of 5-(3-p-cyanophenoxy-2-hydroxy-1-propoxy)-2-(1H-tetrazol-5-yl) chromone in four mammalian species. Toxicol Appl Pharmacol 43:527-534 https://doi.org/10.1016/S0041-008X(78)80012-X
  23. Nemeth K, Plumb GW, Berrin JG, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM & Kroon PA (2003). Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42:29-42 https://doi.org/10.1007/s00394-003-0397-3
  24. Ni Y, Turner D, Yates K & Tizard I (2007). Stabilization of growth factors relevant to wound healing by a plant cell wall biomaterial. Planta Med 73:1260-1266 https://doi.org/10.1055/s-2007-990225
  25. Ollila F, Halling K, Vuorela P, Vuorela H & Slotte JP (2002). Characterization of flavonoid--biomembrane interactions. Arch Biochem Biophys 399:103-108 https://doi.org/10.1006/abbi.2001.2759
  26. Olthof MR, Hollman PC, Vree TB & Katan MB (2000). Bioavailabilities of quercetin-3-glucoside and quercetin-4'-glucoside do not differ in humans. J Nutr 130:1200-1203 https://doi.org/10.1093/jn/130.5.1200
  27. Paine MF & Fisher MB (2000). Immunochemical identification of UGT isoforms in human small bowel and in caco-2 cell monolayers. Biochem Biophys Res Commun 14:1053-1057 https://doi.org/10.1006/bbrc.2000.3064
  28. Park YG, Park MY, Sung MK & Kwon H (2005). Study on the intake pattern of health intended foods depending on inclusion of proclaimed health functional food materials. Journal of the Korean Society of Food Science and Nutrition 34:374-379 https://doi.org/10.3746/jkfn.2005.34.3.374
  29. Saccu D, Bogoni P & Procida G (2001). Aloe exudate: characterization by reversed phase HPLC and headspace GC-MS. J Agric Food Chem 49:4526-4530 https://doi.org/10.1021/jf010179c
  30. Speranza G, Morelli CF, Tubaro A, Altinier G, Durì L & Manitto P (2005). Aloeresin I, an anti-inflammatory 5-methylchromone from cape aloe. Planta Med 71:79-81 https://doi.org/10.1055/s-2005-837756
  31. Tammela P, Laitinen L, Galkin A, Wennberg T, Heczko R, Vuorela H, Slotte JP & Vuorela P (2004). Permeability characteristics and membrane affinity of flavonoids and alkyl gallates in Caco-2 cells and in phospholipid vesicles. Arch Biochem Biophys 425:193-199 https://doi.org/10.1016/j.abb.2004.03.023
  32. Teng ZH, Zhou SY, Ran YH, Liu XY, Yang RT, Yang X, Yuan CJ & Mei QB (2007). Cellular absorption of anthraquinones emodin and chrysophanol in human intestinal Caco-2 cells. Biosci Biotechnol Biochem 71:1636-1643 https://doi.org/10.1271/bbb.70025
  33. Vaidyanathan JB & Walle T (2002). Glucuronidation and sulfation of the tea flavonoid (-)-epicatechin by the human and rat enzymes. Drug Metab Dispos 30:897-903 https://doi.org/10.1124/dmd.30.8.897
  34. Vereczkey L, Jemnitz K, Monostory K, Veres Z & Kóbori L (2005). The role of drug metabolizing enzymes in the effect and side-effect of the drugs. Orv Hetil 146:947-952
  35. Walgren RA, Lin JT, Kinne RK & Walle T (2000). Cellular uptake of dietary flavonoid quercetin 4'-beta-glucoside by sodium-dependent glucose transporter SGLT1. J Pharmacol Exp Ther 294:837-843
  36. Wilkinson AP, Gee JM, Dupont MS, Needs PW, Mellon FA, Williamson G & Johnson IT (2003). Hydrolysis by lactase phlorizin hydrolase is the first step in the uptake of daidzein glucosides by rat small intestine in vitro. Xenobiotica 33:255-264 https://doi.org/10.1080/0049825021000058088