全部 标题 作者
关键词 摘要


Inhibition of Aldose Reductase by Gentiana lutea Extracts

DOI: 10.1155/2012/147965

Full-Text   Cite this paper   Add to My Lib

Abstract:

Accumulation of intracellular sorbitol due to increased aldose reductase (ALR2) activity has been implicated in the development of various secondary complications of diabetes. Thus, ALR2 inhibition could be an effective strategy in the prevention or delay of certain diabetic complications. Gentiana lutea grows naturally in the central and southern areas of Europe. Its roots are commonly consumed as a beverage in some European countries and are also known to have medicinal properties. The water, ethanol, methanol, and ether extracts of the roots of G. lutea were subjected to in vitro bioassay to evaluate their inhibitory activity on the ALR2. While the ether and methanol extracts showed greater inhibitory activities against both rat lens and human ALR2, the water and ethanol extracts showed moderate inhibitory activities. Moreover, the ether and methanol extracts of G. lutea roots significantly and dose-dependently inhibited sorbitol accumulation in human erythrocytes under high glucose conditions. Molecular docking studies with the constituents commonly present in the roots of G. lutea indicate that a secoiridoid glycoside, amarogentin, may be a potential inhibitor of ALR2. This is the first paper that shows G. lutea extracts exhibit inhibitory activity towards ALR2 and these results suggest that Gentiana or its constituents might be useful to prevent or treat diabetic complications. 1. Introduction According to the latest WHO estimates, currently approximately 200 million people all over the world are suffering from diabetes. This may increase to at least 350 million by the year 2025, which could have a severe impact on human health [1]. Prolonged exposure to chronic hyperglycemia in diabetes can lead to various complications affecting the cardiovascular, renal, neurological, and visual systems [2]. Although mechanisms leading to diabetic complications are not completely understood, many biochemical pathways associated with hyperglycemia have been implicated [2]. Among these, the polyol pathway has been extensively studied [3]. Aldose reductase (ALR2; EC: 1.1.1.21) belongs to aldo-keto reductases (AKR) super family. It is the first and rate-limiting enzyme in the polyol pathway where it reduces glucose to sorbitol utilizing NADPH as a cofactor. Subsequently, sorbitol dehydrogenase catalyzes the conversion of sorbitol to fructose, thus constituting the polyol pathway [3]. Accumulation of sorbitol leads to osmotic swelling, changes in membrane permeability, and also oxidative stress culminating in tissue injury [4]. Experimental animal models suggest

References

[1]  S. Wild, G. Roglic, A. Green, R. Sicree, and H. King, “Global prevalence of diabetes: estimates for the year 2000 and projections for 2030,” Diabetes Care, vol. 27, no. 5, pp. 1047–1053, 2007.
[2]  M. Brownlee, “Biochemistry and molecular cell biology of diabetic complications,” Nature, vol. 414, no. 6865, pp. 813–820, 2001.
[3]  J. H. Kinoshita, “A thirty year journey in the polyol pathway,” Experimental Eye Research, vol. 50, no. 6, pp. 567–573, 1990.
[4]  A. Bhatnagar and S. K. Srivastava, “Aldose reductase: congenial and injurious profiles of an enigmatic enzyme,” Biochemical Medicine and Metabolic Biology, vol. 48, no. 2, pp. 91–121, 1992.
[5]  P. F. Kador, J. H. Kinoshita, and N. E. Sharpless, “Aldose reductase inhibitors: a potential new class of agents for the pharmacological control of certain diabetic complications,” Journal of Medicinal Chemistry, vol. 28, no. 7, pp. 841–849, 1985.
[6]  N. Hotta, T. Toyota, K. Matsuoka et al., “Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study,” Diabetes Care, vol. 24, no. 10, pp. 1776–1782, 2001.
[7]  P. Raskin and J. Rosenstock, “Aldose reductase inhibitors and diabetic complications,” The American Journal of Medicine, vol. 83, no. 2, pp. 298–306, 1987.
[8]  M. A. Pfeifer, M. P. Schumer, and D. A. Gelber, “Aldose reductase inhibitors: the end of an era or the need for different trial designs?” Diabetes, vol. 46, supplement 2, pp. S82–S89, 1997.
[9]  P. J. Oates and B. L. Mylari, “Aldose reductase inhibitors: therapeutic implications for diabetic complications,” Expert Opinion on Investigational Drugs, vol. 8, no. 12, pp. 2095–2119, 1999.
[10]  P. F. Kador, W. G. Robison, and J. H. Kinoshita, “The pharmacology of aldose reductase inhibitors,” Annual Review of Pharmacology and Toxicology, vol. 25, pp. 691–714, 1985.
[11]  P. Suryanarayana, P. A. Kumar, M. Saraswat, J. M. Petrash, and G. B. Reddy, “Inhibition of aldose reductase by tannoid principles of Emblica officinalis: implications for the prevention of sugar cataract,” Molecular Vision, vol. 10, pp. 148–154, 2004.
[12]  P. Suryanarayana, M. Saraswat, J. M. Petrash, and G. B. Reddy, “Emblica officinalis and its enriched tannoids delay streptozotocin-induced diabetic cataract in rats,” Molecular Vision, vol. 24, pp. 1291–1297, 2007.
[13]  M. Saraswat, P. Muthenna, P. Suryanarayana, J. M. Petrash, and G. B. Reddy, “Dietary sources of aldose reductase inhibitors: prospects for alleviating diabetic complications,” Asia Pacific Journal of Clinical Nutrition, vol. 17, no. 4, pp. 558–565, 2008.
[14]  P. Muthenna, P. Suryanarayana, S. Gunda, J. M. Petrash, and G. B. Reddy, “Inhibition of aldose reductase by dietary antioxidant curcumin: mechanism of inhibition, specificity and significance,” FEBS Letters, vol. 583, no. 22, pp. 3637–3642, 2009.
[15]  G. B. Reddy, P. Muthenna, C. Akileshwari, M. Saraswat, and J. M. Petrash, “Inhibition of aldose reductase and sorbitol accumulation by dietary rutin,” Current Science, vol. 101, no. 9, pp. 1191–1197, 2011.
[16]  M. Daniel and S. D. Sabnis, “Chemical systematics of family Gentianaceae,” Current Science, vol. 47, no. 4, pp. 109–111, 1978.
[17]  J. M. Petrash, T. M. Harter, C. S. Devine et al., “Involvement of cysteine residues in catalysis and inhibition of human aldose reductase. Site-directed mutagenesis of Cys-80, -298, and -303,” The Journal of Biological Chemistry, vol. 267, no. 34, pp. 24833–24840, 1992.
[18]  J. I. Malone, G. Knox, S. Benford, and T. A. Tedesco, “Red cell sorbitol: an indicator of diabetic control,” Diabetes, vol. 29, no. 11, pp. 861–864, 1980.
[19]  R. H?nsel and O. Sticher, Pharmakognosie-Phytopharmazie, vol. 8, Springer, Heidelberg, Germany, 2007.
[20]  M. Wichtl, Teedrogen und Phytotherapeutika, vol. 4, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, Germany, 2002.
[21]  A. Aberham, S. Schwaiger, H. Stuppner, and M. Ganzera, “Quantitative analysis of iridoids, secoiridoids, xanthones and xanthone glycosides in Gentiana lutea L. roots by RP-HPLC and LC-MS,” Journal of Pharmaceutical and Biomedical Analysis, vol. 45, no. 3, pp. 437–442, 2007.
[22]  N. ?ztürk, S. Korkmaz, Y. ?ztürk, and K. H. Ba?er, “Effects of gentiopicroside, sweroside and swertiamarine, secoiridoids from gentian (Gentiana lutea ssp. symphyandra), on cultured chicken embryonic fibroblasts,” Planta Medica, vol. 72, no. 4, pp. 289–294, 2006.
[23]  I. Citová, M. Ganzera, H. Stuppner, and P. Solich, “Determination of gentisin, isogentisin, and amarogentin in Gentiana lutea L. by capillary electrophoresis,” Journal of Separation Science, vol. 31, no. 1, pp. 195–200, 2008.
[24]  A. Singh, “Phytochemicals of gentianaceae: a review of pharmacological properties,” International Journal of Pharmaceutical Sciences and Nanotechnology, vol. 1, no. 1, pp. 33–36, 2008.
[25]  A. Schmieder, S. Schwaiger, A. Csordas et al., “Isogentisin—a novel compound for the prevention of smoking-caused endothelial injury,” Atherosclerosis, vol. 194, no. 2, pp. 317–325, 2007.
[26]  B. Crosas, D. J. Hyndman, O. Gallego et al., “Human aldose reductase and human small intestine aldose reductase are efficient retinal reductases: consequences for retinoid metabolism,” The Biochemical Journal, vol. 373, part 3, pp. 973–979, 2003.
[27]  A. D. Morrison, R. S. Clements, and A. I. Winegrad, “Effects of elevated glucose concentrations on the metabolism of the aortic wall,” The Journal of Clinical Investigation, vol. 51, no. 12, pp. 3114–3123, 1972.
[28]  G. B. Reddy, A. Satyanarayana, N. Balakrishna et al., “Erythrocyte aldose reductase activity and sorbitol levels in diabetic retinopathy,” Molecular Vision, vol. 14, pp. 593–601, 2008.
[29]  D. R. Tomlinson, E. J. Stevens, and L. T. Diemel, “Aldose reductase inhibitors and their potential for the treatment of diabetic complications,” Trends in Pharmacological Sciences, vol. 15, no. 8, pp. 293–297, 1994.
[30]  N. ?ztürk, T. Herekman-Demir, Y. ?ztürk, B. Bozan, and K. H. C. Ba?er, “Choleretic activity of Gentiana lutea ssp. symphyandra in rats,” Phytomedicine, vol. 5, no. 4, pp. 283–288, 1998.
[31]  A. Ku?ar, A. Zupan?i?, M. ?entjurc, and D. Bari?evi?, “Free radical scavenging activities of yellow gentian (Gentiana lutea L.) measured by electron spin resonance,” Human and Experimental Toxicology, vol. 25, no. 10, pp. 599–604, 2006.
[32]  A. Mathew, A. D. Taranalli, and S. S. Torgal, “Evaluation of anti-inflammatory and wound healing activity of Gentiana lutea rhizome extracts in animals,” Pharmaceutical Biology, vol. 42, no. 1, pp. 8–12, 2004.
[33]  J. Bruneton, Pharmacognosy, Lavoisier Publishing, Paris, France, 1999.
[34]  M. Hostettmann-Kaldas, K. Hostettmann, and O. Sticher, “Xanthones, flavones and secoiridoids of American Gentiana species,” Phytochemistry, vol. 20, no. 3, pp. 443–446, 1981.

Full-Text

comments powered by Disqus