Bioactive compounds isolated from apple, tea, and ginger protect against dicarbonyl induced stress in cultured human retinal epithelial cells
Abstract
Background Methylglyoxal (MGO) is known to be a major precursor of advanced glycation end products (AGEs) which are linked to diabetes and its related complications. Naturally occurring bioactive compounds could play an important role in countering AGEs thereby minimizing the risk associated with their formation.Methods In this study, eight specific bioactive compounds isolated from apple, tea and ginger were evaluated for their AGEs scavenging activity using Human Retinal Pigment Epithelial (H-RPE) cells treated with MGO.Results Among the eight specific compounds evaluated, (-)-epigallocatechin 3-gallate (EGCG) from tea, phloretin in apple, and [6]-shogaol and [6]-gingerol from ginger were found to be most effective in preventing MGO-induced cytotoxicity in the epithelial cells. Investigation of possible underlying mechanisms suggests that that these compounds could act by modulating key regulative detoxifying enzymes via modifying nuclear factor-erythroid 2-related factor 2 (Nrf2) function. MGO-induced cytotoxicity led to increased levels of AGEs causing increase in Nε-(Carboxymethyl) lysine (CML) and glutathione (GSH) levels and over expression of receptor for advanced glycation end products (RAGE). Data also showed that translocation of Nrf2 from cytosol to nucleus was inhibited, which decreased the expression of detoxifying enzyme like heme oxygenase-1 (HO-1). The most potent bioactive compounds scavenged dicarbonyl compounds, inhibited AGEs formation and significantly reduced carbonyl stress by Nrf2 related pathway and restoration of HO-1 expression.Conclusions These findings demonstrated the protective effect of bioactive compounds derived from food sources against MGO-induced carbonyl stress through activation of the Nrf2 related defense pathway, which is of significant importance for therapeutic interventions in complementary treatment/management of diabetes-related complications.
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In the presence of MGO, the translocation of Nrf2 from the cytosol to the nucleus is inhibited, which results in a decreased expression of detoxifying enzymes such as heme oxygenase-1.
“In fact, in the presence of MGO, the translocation of Nrf2 from the cytosol to the nucleus is inhibited, which results in a decreased expression of detoxifying enzymes such as heme oxygenase-1 [195].”
From GANAB and N-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review (2022) · cites this paper as [195]
Cites
Advanced Glycation End Products: Sparking the Development of Diabetic Vascular Injury
Goldin, A., Beckman, J. A., Schmidt, A. M., & Creager, M. A. (2006) · Circulation · doi:10.1161/circulationaha.106.621854 · Cited by 2,261 · see citing works
Flavonoid intake and risk of chronic diseases
Knekt, P., Kumpulainen, J. T., Järvinen, R., Rissanen, H. A., Heliövaara, M., Reunanen, A., Hakulinen, T., & Aromaa, A. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.3.560 · Cited by 1,748 · see citing works
ARPE-19, A Human Retinal Pigment Epithelial Cell Line with Differentiated Properties
Dunn, K. C., Aotaki-Keen, A. E., Putkey, F. R., & Hjelmeland, L. M. (1996) · Experimental Eye Research · doi:10.1006/exer.1996.0020 · Cited by 1,334 · see citing works
Molecular mechanisms of Nrf2‐mediated antioxidant response
Li, W., & Kong, A. T. (2008) · Molecular Carcinogenesis · doi:10.1002/mc.20465 · Cited by 786 · see citing works
Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation endproducts
Thornalley, P. J. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.08.013 · Cited by 683 · see citing works
Na, H., & Surh, Y. (2007) · Food and Chemical Toxicology · doi:10.1016/j.fct.2007.10.006 · Cited by 486 · see citing works
Al-Amin, Z. M., Thomson, M., Al‐Qattan, K. K., Peltonen‐Shalaby, R., & Ali, M. (2006) · British Journal Of Nutrition · doi:10.1079/bjn20061849 · Cited by 420 · see citing works
Sabu, M. C., Smitha, K., & Kuttan, R. (2002) · Journal of Ethnopharmacology · doi:10.1016/s0378-8741(02)00217-9 · Cited by 418 · see citing works
Spilsbury, K., Garrett, K. L., Shen, W.-Y., Constable, I. J., & Rakoczy, P. E. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64525-7 · Cited by 395 · see citing works
Song, Y., Manson, J. E., Buring, J. E., Sesso, H. D., & Liu, S. (2005) · Journal of the American College of Nutrition · doi:10.1080/07315724.2005.10719488 · Cited by 389 · see citing works
Rage and arthritis: The G82S polymorphism amplifies the inflammatory response
Hofmann, M. A., Drury, S., Hudson, B. I., Gleason, M. R., Qu, W., Lu, Y., Lalla, E., Chitnis, S., Monteiro, J., Stickland, M. H., et al. (2002) · Genes & Immunity · doi:10.1038/sj.gene.6363861 · Cited by 383 · see citing works
Role of advanced glycation end products in cardiovascular disease
Hegab, Z. (2012) · World Journal of Cardiology · doi:10.4330/wjc.v4.i4.90 · Cited by 354 · see citing works
Bordia, A., Verma, S. K., & Srivastava, K. C. (1997) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/s0952-3278(97)90587-1 · Cited by 352 · see citing works
Tsuneki, H., Ishizuka, M., Terasawa, M., Wu, J.-B., Sasaoka, T., & Kimura, I. (2004) · BMC Pharmacology · doi:10.1186/1471-2210-4-18 · Cited by 311 · see citing works
Quercetin Inhibits Advanced Glycation End Product Formation by Trapping Methylglyoxal and Glyoxal
Li, X., Zheng, T., Sang, S., & Lv, L. (2014) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf504132x · Cited by 291 · see citing works
Self-citationEffect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats
Bhandari, U., kanojia, R., & Pillai, K. K. (2005) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2004.11.011 · Cited by 276 · see citing works
Ojewole, J. A. O. (2006) · Phytotherapy Research · doi:10.1002/ptr.1952 · Cited by 272 · see citing works
Yeh, C., & Yen, G. (2006) · Journal of Nutrition · doi:10.1093/jn/136.1.11 · Cited by 213 · see citing works
Tea Polyphenol (−)-Epigallocatechin-3-Gallate: A New Trapping Agent of Reactive Dicarbonyl Species
Sang, S., Shao, X., Bai, N., Lo, C., Yang, C. S., & Ho, C. (2007) · Chemical Research in Toxicology · doi:10.1021/tx700190s · Cited by 212 · see citing works
Self-citationGinger and its Health Claims: Molecular Aspects
Butt, M. S., & Sultan, M. T. (2011) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408391003624848 · Cited by 204 · see citing works
Sang, S., Hong, J., Wu, H. C., Liu, J., Yang, C. S., Pan, M., Badmaev, V., & Ho, C. (2009) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf9027443 · Cited by 187 · see citing works
Self-citationApple Polyphenols, Phloretin and Phloridzin: New Trapping Agents of Reactive Dicarbonyl Species
Shao, X., Bai, N., He, K., Ho, C., Yang, C. S., & Sang, S. (2008) · Chemical Research in Toxicology · doi:10.1021/tx800227v · Cited by 186 · see citing works
Self-citationYang, M.-H., Wang, C., & Chen, H. (2001) · The Journal of Nutritional Biochemistry · doi:10.1016/s0955-2863(00)00140-6 · Cited by 180 · see citing works
Nagaraj, R. H., Sarkar, P., Mally, A., Biemel, K. M., Lederer, M. O., & Padayatti, P. S. (2002) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(02)00067-x · Cited by 172 · see citing works
Grove, K. A., & Lambert, J. D. (2010) · Journal of Nutrition · doi:10.3945/jn.109.115972 · Cited by 171 · see citing works
Genistein Inhibits Advanced Glycation End Product Formation by Trapping Methylglyoxal
Lv, L., Shao, X., Chen, H., Ho, C., & Sang, S. (2011) · Chemical Research in Toxicology · doi:10.1021/tx100457h · Cited by 165 · see citing works
Self-citationAntihyperglycemic Effect of Oolong Tea in Type 2 Diabetes
Hosoda, K., Wang, M.-F., Liao, M.-L., Chuang, C.-K., Iha, M., Clevidence, B. A., & Yamamoto, S. (2003) · Diabetes Care · doi:10.2337/diacare.26.6.1714 · Cited by 164 · see citing works
Keum, Y., Owuor, E. D., Kim, B., Hu, R., & Kong, A. (2003) · Pharmaceutical Research · doi:10.1023/a:1025737622815 · Cited by 161 · see citing works
Islam, M., & Choi, H. (2008) · Journal of Medicinal Food · doi:10.1089/jmf.2007.634 · Cited by 160 · see citing works
Nammi, S., Satyanarayana, S., & Roufogalis, B. D. (2009) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2008.00362.x · Cited by 152 · see citing works
Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin-induced diabetic rats
Shanmugam, K. R., Korivi, M., Nishanth, K., & Reddy, K. S. (2010) · Food and Chemical Toxicology · doi:10.1016/j.fct.2010.12.013 · Cited by 143 · see citing works
Madkor, H. R., Mansour, S. W., & Ramadan, G. (2010) · British Journal Of Nutrition · doi:10.1017/s0007114510004927 · Cited by 134 · see citing works
Teerlink, T., Barto, R., ten Brink, H. J., & Schalkwijk, C. G. (2004) · Clinical Chemistry · doi:10.1373/clinchem.2004.031286 · Cited by 134 · see citing works
Cytotoxic, cytoprotective and antioxidant effects of isolated phenolic compounds from fresh ginger
Peng, F., Tao, Q., Wu, X., Dou, H., Spencer, S. D., Mang, C.-Y., Xu, L., Sun, L., Zhao, Y., Li, H., et al. (2012) · Fitoterapia · doi:10.1016/j.fitote.2011.12.028 · Cited by 130 · see citing works
Qi, L., Meigs, J. B., Liu, S., Manson, J. E., Mantzoros, C. S., & Hu, F. B. (2006) · Diabetes Care · doi:10.2337/dc06-0221 · Cited by 117 · see citing works
Weng, C., Chen, M.-J., Yeh, C., & Yen, G. (2011) · New Biotechnology · doi:10.1016/j.nbt.2011.05.003 · Cited by 106 · see citing works
METHYLGLYOXAL, DIABETES MELLITUS AND DIABETIC COMPLICATIONS
Jagt, D. L. V. (2008) · Drug metabolism and drug interactions · doi:10.1515/dmdi.2008.23.1-2.93 · Cited by 104 · see citing works
Antiglycating potential of Zingiber officinalis and delay of diabetic cataract in rats.
Saraswat, M., Suryanarayana, P., Reddy, P. Y., Patil, M. A., Balakrishna, N., & Reddy, G. B. (2010) · PubMed Central · Cited by 97 · see citing works
Sadowska‐Bartosz, I., Galiniak, S., & Bartosz, G. (2014) · Molecules · doi:10.3390/molecules19044880 · Cited by 91 · see citing works
Methylglyoxal and Advanced Glycation Endproducts: New Therapeutic Horizons?
Desai, B. S. P. K., & Wu, B. S. P. L. (2007) · Recent Advances in Cardiovascular Drug Discovery (Formerly Recent Patents on Cardiovascular Drug Discovery) · doi:10.2174/157489007780832498 · Cited by 89 · see citing works
Powdered green tea has antilipogenic effect on Zucker rats fed a high‐fat diet
Hasegawa, N., Yamda, N., & Mori, M. (2003) · Phytotherapy Research · doi:10.1002/ptr.1177 · Cited by 87 · see citing works
Growth factors and their receptors in the retina and pigment epithelium
Tanihara, H., Inatani, M., & Honda, Y. (1997) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(96)00028-6 · Cited by 82 · see citing works
Kato, A., Higuchi, Y., Goto, H., et al. (2006) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf061599a · Cited by 77 · see citing works
Rutter, Sell, Fraser, Obrenovich, Zito, Starke-Reed, & Monnier (2003) · International Journal for Vitamin and Nutrition Research · doi:10.1024/0300-9831.73.6.453 · Cited by 76 · see citing works
Anti-Inflammatory Effects of the Advanced Glycation End Product Inhibitor LR-90 in Human Monocytes
Figarola, J. L., Shanmugam, N., Natarajan, R. D., & Rahbar, S. (2007) · Diabetes · doi:10.2337/db06-0936 · Cited by 73 · see citing works
Novel inhibitors of glycation and AGE formation
Rahbar, S. (2007) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-007-0021-x · Cited by 69 · see citing works
Kadnur, S. V., & Goyal, R. K. (2005) · PubMed · Cited by 67 · see citing works
Shanmugam, K. R. (2011) · The Chinese Journal of Physiology · doi:10.4077/cjp.2011.amm006 · Cited by 62 · see citing works
Jeong-Ah, Y. A. N. G., Choi, J.-H., & Rhee, S. (1999) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.45.337 · Cited by 58 · see citing works
Jin, J., Li, M., Zhao, Z., et al. (2015) · Phytomedicine · doi:10.1016/j.phymed.2015.03.003 · Cited by 43 · see citing works
Naito, Y., & Yoshikawa, T. (2009) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181b6e7a1 · Cited by 41 · see citing works
Zúñiga-Toalá, A., Zatarain-Barrón, Z. L., Hernández‐Pando, R., et al. (2013) · Phytomedicine · doi:10.1016/j.phymed.2013.03.020 · Cited by 29 · see citing works
Holik, A., Lieder, B., Somoza, M. M., & Somoza, V. (2013) · Food & Function · doi:10.1039/c3fo60097a · Cited by 27 · see citing works
Kim, Y. S., Jung, D. H., Kim, N. H., et al. (2007) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2007.02.017 · Cited by 25 · see citing works
Effect of green tea catechin on arachidonic acid cascade in chronic cadmium‐poisoned rats
Choi, J., Chang, H., & Rhee, S. (2002) · Asia Pacific Journal of Clinical Nutrition · doi:10.1046/j.1440-6047.2002.00305.x · Cited by 25 · see citing works
Kim, S.-J., Kim, J. M., Shim, S. H., et al. (2014) · Journal of Functional Foods · doi:10.1016/j.jff.2013.12.028 · Cited by 24 · see citing works
Rhee, S., Kim, M., & Kwag, O. (2002) · Asia Pacific Journal of Clinical Nutrition · doi:10.1046/j.1440-6047.2002.00312.x · Cited by 22 · see citing works
Tea Flavanols Block Advanced Glycation of Lens Crystallins Induced by Dehydroascorbic Acid
Zhu, Y., Zhao, Y., Wang, P., et al. (2014) · Chemical Research in Toxicology · doi:10.1021/tx500430z · Cited by 21 · see citing works
Self-citationAkhani, S. P., Vishwakarma, S., & Goyal, R. K. (2005) · Indian Journal of Pharmaceutical Sciences · Cited by 3 · see citing works
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De Masi, R., & Orlando, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137373 · Cited by 20 · see citing works
- Authors
- Sampath, C., Zhu, Y., Sang, S., & Ahmedna, M.
- Affiliations
- Qatar University (QA)
- North Carolina Agricultural and Technical State University (US)
- Corresponding author
- Ahmedna, Mohamed
- Venue
- Phytomedicine
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 23
- Issue
- 2
- Pages
- 200-213
- ISSN
- 0944-7113 (ISSN-L)
- OpenAlex
- W2229729265
- Cited by
- 48
- References
- 59
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 3 · 2019: 8 · 2018: 2 · 2017: 7 · 2016: 4
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Phytomedicine (publishedVersion)
- PubMed (publishedVersion)
- Qatar University QSpace (Qatar University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- methylglyoxal, advanced glycation end products, carbonyl stress, Nrf2, heme oxygenase-1, retinal pigment epithelial cells, epigallocatechin gallate, phloretin, shogaol, gingerol, RAGE, glutathione, diabetes complications, apple, tea, ginger
- MeSH terms
- Receptor for Advanced Glycation End Products, Catechin, Catechols, Cell Line, Epithelial Cells, Fatty Alcohols, Glutathione, Humans, Lysine, Phloretin, Pyruvaldehyde, Tea, Glycation End Products, Advanced, Protective Agents, Zingiber officinale, Malus, NF-E2-Related Factor 2, Heme Oxygenase-1, Retinal Pigment Epithelium, Phytochemicals
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