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Inhibition of Protein Glycation by Combined Antioxidant and Antiglycation Constituents from a Phenolic Fraction of Sage (Salvia officinalis L.)

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Abstract

Disturbed advanced glycation end products (AGEs)-oxidative stress axis is strongly linked to vascular complications observed in diabetes and other metabolic conditions. Salvia officinalis L. (sage) is a medicinal plant used as an ingredient in foods and beverages and displays a wide range of biological and pharmacological activities including anti-diabetic effects. However, no study has assessed its anti-glycative potential. The aim of this study is to determine the phenolic compounds associated with the anti-glycation and antioxidant potential of sage methanol extract (SME). SME shows similar effects to aminoguanidine on fluorescent AGEs inhibition. It protects albumin damage from glycation (52.9 vs. 50.3%, respectively) by preventing the loss of protein thiol groups (50.0 vs. 44.3%, respectively) and by reducing protein carbonyl accumulation (67.4 vs. 70.5%, respectively). Moreover, linear regression and multivariate analysis support the efficient contribution of SME antioxidant capacity, as judged by DPPH, TBARS and iron chelating tests, in AGEs suppression. Furthermore, HPLC analysis revealed the presence of verbascoside as a novel phenolic constituent identified in sage leaves and suggests that the protective activity is mostly assigned to the presence of rosmarinic acid, resveratrol, quercetin, rutin and luteolin-7-O-glucoside. Likewise, the screening of SME phenolic content supports the contribution of various antioxidant substances to the observed effects. Therefore, a polyphenol enriched sage extract was able to inhibit the formation of AGEs and protein glycation. Our data unveils the promising properties of sage and its bioactive principles in the management of AGEs-mediated vascular complications observed in diabetes and other metabolic disorders.

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Abbreviations

AG:

Aminoguanidine

AGEs:

Advanced glycation end products

BSA:

Bovine serum albumin

DPPH:

2,2-diphenyl-1-picrylhydrazyl

DNPH:

2,4-dinitrophenylhydrazine

DTNB:

5,5′-dithio-bis(2-nitrobenzoic acid

DW:

Dry weight

FRAP:

Ferrous reducing antioxidant power

HPLC:

High performance liquid chromatography

SME:

Sage methanol extract

OxS:

Oxidative stress

PBS:

Phosphate buffer saline

TBARS:

Thiobarbituric acid-reacting substances

References

  1. Yamagishi S (2012) Potential clinical utility of advanced glycation end product cross-link breakers in age- and diabetes-associated disorders. Rejuvenation Res 15(6):564–572. https://doi.org/10.1089/rej.2012.1335

    Article  CAS  PubMed  Google Scholar 

  2. Ahmed N (2005) Advanced glycation endproducts--role in pathology of diabetic complications. Diabetes Res Clin Pract 67(1):3–21. https://doi.org/10.1016/j.diabres.2004.09.004

    Article  CAS  PubMed  Google Scholar 

  3. Sugimoto K, Yasujima M, Yagihashi S (2008) Role of advanced glycation end products in diabetic neuropathy. Curr Pharm Des 14(10):953–961. https://doi.org/10.2174/138161208784139774

    Article  CAS  PubMed  Google Scholar 

  4. Xu J, Chen LJ, Yu J, Wang HJ, Zhang F, Liu Q, Wu J (2018) Involvement of advanced glycation end products in the pathogenesis of diabetic retinopathy. Cell Physiol Biochem 48(2):705–717. https://doi.org/10.1159/000491897

  5. Forbes JM, Cooper ME, Oldfield MD, Thomas MC (2003) Role of advanced glycation end products in diabetic nephropathy. J Am Soc Nephrol 14(8 Suppl 3):S254–S258. https://doi.org/10.1097/01.asn.0000077413.41276.17

    Article  CAS  PubMed  Google Scholar 

  6. Hedrick CC, Thorpe SR, Fu MX, Harper CM, Yoo J, Kim SM, Wong H, Peters AL (2000) Glycation impairs high-density lipoprotein function. Diabetologia 43(3):312–320. https://doi.org/10.1007/s001250050049

    Article  CAS  PubMed  Google Scholar 

  7. Del Turco S, Basta G (2012) An update on advanced glycation endproducts and atherosclerosis. Biofactors 38(4):266–274. https://doi.org/10.1002/biof.1018

    Article  CAS  PubMed  Google Scholar 

  8. Moldogazieva NT, Mokhosoev IM, Mel'nikova TI, Porozov YB, Terentiev AA (2019) Oxidative stress and advanced lipoxidation and glycation end products (ALEs and AGEs) in aging and age-related diseases. Oxid Med Cell Longev 2019:1–14. https://doi.org/10.1155/2019/3085756

  9. Saremi A, Howell S, Schwenke DC, Bahn G, Beisswenger PJ, Reaven PD (2017) Advanced glycation end products, oxidation products, and the extent of atherosclerosis during the VA diabetes trial and follow-up study. Diabetes Care 40(4):591–598. https://doi.org/10.2337/dc16-1875

  10. Ahmad S, Siddiqui Z (2015) Protein glycation: a firm link to cause metabolic disease and their complications. J Glycomics Lipidomics 5:1000127. https://doi.org/10.4172/2153-0637.1000127

    Article  CAS  Google Scholar 

  11. Ghorbani A, Esmaeilizadeh M (2017) Pharmacological properties of Salvia officinalis and its components. J Tradit Complement Med 7(4):433–440. https://doi.org/10.1016/j.jtcme.2016.12.014

  12. Ben Khedher MR, Hammami M, Arch JRS, Hislop DC, Eze D, Wargent ET, Kępczyńska MA, Zaibi MS (2018) Preventive effects of Salvia officinalis leaf extract on insulin resistance and inflammation in a model of high fat diet-induced obesity in mice that responds to rosiglitazone. PeerJ 6:e4166. https://doi.org/10.7717/peerj.4166

  13. Khedher MRB, Khedher SB, Chaieb I, Tounsi S, Hammami M (2017) Chemical composition and biological activities of Salvia officinalis essential oil from Tunisia. EXCLI J 16:160–173. https://doi.org/10.17179/excli2016-832

  14. Zengin G, Llorent-Martínez EJ, Córdova MLF-d, Bahadori MB, Mocan A, Locatelli M, Aktumsek A (2018) Chemical composition and biological activities of extracts from three Salvia species: S. blepharochlaena, S. euphratica var. leiocalycina, and S. verticillata subsp. amasiaca. Ind Crop Prod 111:11–21. https://doi.org/10.1016/j.indcrop.2017.09.065

  15. Brownlee M, Vlassara H, Kooney A, Ulrich P, Cerami A (1986) Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking. Science 232(4758):1629–1632. https://doi.org/10.1126/science.3487117

    Article  CAS  PubMed  Google Scholar 

  16. Thornalley PJ (2003) Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation endproducts. Arch Biochem Biophys 419(1):31–40. https://doi.org/10.1016/j.abb.2003.08.013

    Article  CAS  PubMed  Google Scholar 

  17. Ramkissoon JS, Mahomoodally MF, Ahmed N, Subratty AH (2013) Antioxidant and anti-glycation activities correlates with phenolic composition of tropical medicinal herbs. Asian Pac J Trop Med 6(7):561–569. https://doi.org/10.1016/s1995-7645(13)60097-8

    Article  CAS  PubMed  Google Scholar 

  18. Ou J, Huang J, Wang M, Ou S (2017) Effect of rosmarinic acid and carnosic acid on AGEs formation in vitro. Food Chem 221:1057–1061. https://doi.org/10.1016/j.foodchem.2016.11.056

  19. Giménez-Bastida JA, Zielinski H, Piskula M, Zielinska D, Szawara-Nowak D (2017) Buckwheat bioactive compounds, their derived phenolic metabolites and their health benefits. Mol Nutr Food Res 61(7). https://doi.org/10.1002/mnfr.201600475

  20. Jung HA, Park JJ, Min BS, Jung HJ, Islam MN, Choi JS (2015) Inhibition of advanced glycation endproducts formation by Korean thistle, Cirsium maackii. Asian Pac J Trop Med 8(1):1–5. https://doi.org/10.1016/S1995-7645(14)60178-4

    Article  CAS  PubMed  Google Scholar 

  21. Shen Y, Xu Z, Sheng Z (2017) Ability of resveratrol to inhibit advanced glycation end product formation and carbohydrate-hydrolyzing enzyme activity, and to conjugate methylglyoxal. Food Chem 216:153–160. https://doi.org/10.1016/j.foodchem.2016.08.034

    Article  CAS  PubMed  Google Scholar 

  22. Kuo C-T, Liu T-H, Hsu T-H, Lin F-Y, Chen H-Y (2015) Antioxidant and antiglycation properties of different solvent extracts from Chinese olive (Canarium album L.) fruit. Asian Pac J Trop Med 8(12):1013–1021. https://doi.org/10.1016/j.apjtm.2015.11.013

  23. Virgili F, Kobuchi H, Packer L (1998) Procyanidins extracted from Pinus maritima (Pycnogenol): scavengers of free radical species and modulators of nitrogen monoxide metabolism in activated murine RAW 264.7 macrophages. Free Radic Biol Med 24(7–8):1120–1129. https://doi.org/10.1016/s0891-5849(97)00430-9

  24. Zafra-Stone S, Yasmin T, Bagchi M, Chatterjee A, Vinson JA, Bagchi D (2007) Berry anthocyanins as novel antioxidants in human health and disease prevention. Mol Nutr Food Res 51(6):675–683. https://doi.org/10.1002/mnfr.200700002

    Article  CAS  PubMed  Google Scholar 

  25. Fernando PMDJ, Piao MJ, Kang KA, Ryu YS, Hewage SRKM, Chae SW, Hyun JW (2016) Rosmarinic acid attenuates cell damage against UVB radiation-induced oxidative stress via enhancing antioxidant effects in human HaCaT cells. Biomol Ther (Seoul) 24(1):75–84. https://doi.org/10.4062/biomolther.2015.069

    Article  CAS  Google Scholar 

  26. Liu MJ, Li JX, Guo HZ, Lee KM, Qin L, Chan KM (2003) The effects of verbascoside on plasma lipid peroxidation level and erythrocyte membrane fluidity during immobilization in rabbits: a time course study. Life Sci 73(7):883–892. https://doi.org/10.1016/s0024-3205(03)00354-0

    Article  CAS  PubMed  Google Scholar 

  27. Benavente-Garcı́a, O, Castillo J, Lorente J, Ortuño A, Del Rio JA (2000) Antioxidant activity of phenolics extracted from Olea europaea L. leaves. Food Chem 68 (4):457–462 https://doi.org/10.1016/S0308-8146(99)00221-6

  28. Gülçin İ (2010) Antioxidant properties of resveratrol: a structure–activity insight. Innov Food Sci Emerg Technol 11(1):210–218. https://doi.org/10.1016/j.ifset.2009.07.002

    Article  CAS  Google Scholar 

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Acknowledgments

This study is a part of research program of the Research Laboratory LR12ES05 “Nutrition-Functional food and Vascular Health LR-NAFS” and “DGRST-USCR-Mass Spectrometry” financed by the “Tunisian Ministry of Higher Education and Scientific Research”.

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Authors and Affiliations

  1. Research Laboratory LR12ES05 ‘Nutrition - Functional Food & Vascular Health’ Department of Biochemistry, Faculty of Medicine, University of Monastir, 5019, Monastir, Tunisia

    Mohamed Raâfet Ben Khedher & Mohamed Hammami

  2. Institut National de Recherche Scientifique – Centre Armand-Frappier Santé Biotechnologie, Laval, QC, H7V 1B7, Canada

    Mohamed Raâfet Ben Khedher & Mohamed Haddad

  3. Laboratory of Natural Resources Valorization, Department of AgroBioSciences, Mohammed VI Polytechnic University Benguerir, 43150, Ben Guerir, Morocco

    Jawhar Hafsa

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  1. Mohamed Raâfet Ben Khedher
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  4. Mohamed Hammami
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Correspondence to Mohamed Raâfet Ben Khedher.

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The authors declare that they have no financial and personal relationships with other people or organizations that can inappropriately influence their work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Inhibition of protein glycation by combined antioxidant and antiglycation constituents from a phenolic fraction of Salvia officinalis (L.)”

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Ben Khedher, M.R., Hafsa, J., Haddad, M. et al. Inhibition of Protein Glycation by Combined Antioxidant and Antiglycation Constituents from a Phenolic Fraction of Sage (Salvia officinalis L.). Plant Foods Hum Nutr 75, 505–511 (2020). https://doi.org/10.1007/s11130-020-00838-8

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