植物多酚通过RAGE/MAPK/NF-κB通路抑制AGEs诱导的炎症反应研究进展

摘要/Abstract

摘要： 晚期糖基化终末产物（Advanced glycation end products, AGEs）是在美拉德反应末期，蛋白质、氨基酸、脂类或核酸等的游离氨基与还原糖（葡萄糖、果糖、戊糖等）的羧基进行反应后产生的一类稳定产物。AGEs可以与AGE受体（Receptor for advanced glycation end product, RAGE）相互作用，启动其下游的相关信号通路从而诱导氧化应激和炎症反应。植物多酚能抑制AGEs诱导的RAGE上调，减少NF-κB磷酸化和MAPKs的活化，并显著降低炎症介质的基因表达，包括TNF-α，IL-1β和IL-6等。基于此，论文全面综述了植物多酚通过RAGE/MAPK/NF-κB信号通路调节AGEs诱导的炎症因子基因表达的作用机制，以期为研发植物多酚作为预防糖尿病的保健食品或药品提供一定的科学依据。

关键词: 植物多酚, 晚期糖基化终末产物（AGEs）, 核转录因子（NF-κB）, 炎症反应

Abstract: Advanced glycation end products (AGEs) are a stable final product of a class of stable end products produced after the reaction of the free amino and reduced sugar (glucose, fructose, sugar, etc.) of large molecular substances such as proteins, amino acids, lipids or nucleic acids at the end of the Maillard reaction. AGEs can interact with AGE subjects (RAGEs) to activate certain signaling paths downstream to induce oxidative stress and inflammation. Plant polyphenols inhibit AGEs-induced RAGE increases, reduce NF-κB phosphorylation and MAPKs, and significantly reduce gene expression of inflammatory media, including TNF-α, IL-1 beta and IL-6. Therefore, this paper summarizes the mechanism of action of RAGE/MAPK/NF-κB signaling path, and the relationship with AGEs-induced inflammatory response, and summarizes the mechanism of plant polyphenols to the gene expression of inflammatory factors through this signaling path, with a view to providing a scientific basis for the development of plant polyphenols as a health food or medicine for the prevention of diabetes.

Key words: plant polyphenols, advanced glycation end products (AGEs), nuclear transcription factor (NF-κB), inflammatory response

中图分类号:

TS201.6

周子艺夏晓霞冉欢陈媛媛雷小娟赵吉春曾凯芳明建. 植物多酚通过RAGE/MAPK/NF-κB通路抑制AGEs诱导的炎症反应研究进展[J]. 食品科学, 0, (): 0-0.

JIan Ming. Plant polyphenols inhibit AGEs-induced inflammatory responses through the AGE/MAPK/NF-κB signaling path: A review[J]. FOOD SCIENCE, 0, (): 0-0.

参考文献

[1] HENLE T. Protein-bound advanced glycation endproducts (AGEs) as bioactive amino acid derivatives in food[J]. Amino Acids, 2005, 29: 313-322. DOI: 10.1007/s00726-005-0200-2
[2] KELLOW N J, COUGHLAN M T. Effect of diet-derived advanced glycation end products on inflammation[J]. Nutrition Reviews, 2015, 73(11): 737-759. DOI: 10.1093/nutrit/nuv030
[3] ZHOU Qian, GONG Jun, WANG Mingfu. et al. Phloretin and its methylglyoxal adduct: Implications against advanced glycation end products-induced inflammation in endothelial cells[J]. Food and Chemical Toxicology, 2019, 129: 291-300. DOI: 10.1016/j.fct.2019. 05.004
[4] YU Wenzhe, TAO Mengru, ZHAO Yueliang, et al. 4′-Methoxyresveratrol alleviated AGE-induced inflammation via RAGE-mediated NF-κB and NLRP3 inflammasome pathway[J]. Molecules, 2018, 23(6): 1447. DOI: 10.3390/molecules23061447
[5] PENG Xiaofang, MA Jinyu, CHEN Feng, et al. Naturally occurring inhibitors against the formation of advanced glycation end-products[J]. Food and Function, 2011, 2(6): 289-301. DOI: 10.1039/c1fo10034c
[6] CHUYEN N V. Toxicity of the AGEs generated from the Maillard reaction: on the relationship of food-AGEs and biological-AGEs[J]. Molecular Nutrition and Food Research, 2006, 50(12): 1140-1149. DOI: 10.1002/mnfr.200600144
[7] LUND M N, RAY C A. Control of Maillard reactions in foods: strategies and chemical mechanisms[J]. Journal of Agricultural and Food Chemistry, 2017, 65(23): 4537-4552. DOI: 10.1021/acs.jafc.7b00882
[8] 杨洁, 孙捷, 王晓静. 晚期糖基化终末产物抑制剂的研究进展[J]. 中国药物化学杂志, 2019, 29(5): 398-406. DOI: CNKI: SUN: ZGYH.0.2019-05-016
[9] POULSEN M W, HEDEGAARD R V, ANDERSEN J M, et al. Advanced glycation endproducts in food and their effects on health[J]. Food and Chemical Toxicology, 2013, 60: 10-37. DOI: 10.1016/j.fct.2013.06.052
[10] ZHU Zongshuai, HUANG Ming, CHENG Yiqun, et al. A comprehensive review of Nε-carboxymethyllysine and Nε-carboxyethyllysine in thermal processed meat products[J]. Trends in Food Science and Technology, 2020, 98: 30-40. DOI: 10.1016/j. tifs.2020.01.021
[11] NIE Chenzhipeng, LI Yan, QIAN Haifeng, et al. Advanced glycation end products in food and their effects on intestinal tract[J]. Critical Reviews in Food Science and Nutrition, 2020:1-13. DOI: 10.1080/10408398.2020.1863904
[12] ZAMORA R, HIDALGO F J. Coordinate contribution of lipid oxidation and Maillard reaction to the nonenzymatic food browning[J]. Critical Reviews in Food Science and Nutrition, 2005, 45(1): 49-59. DOI: 10.1080/10408690590900117
[13] CONTRERAS C L, SEVILLA E G, NOVAKOFSKI K C. Role of dietary advanced glycation end products in diabetes mellitus[J]. Journal of Evidence-Based Complementary and Alternative Medicine. 2013, 18(1): 50-66. DOI: 10.1177/2156587212460054
[14] FOURNET M, BONTé F, DESMOULIèRE A. Glycation damage: a possible hub for major pathophysiological disorders and aging[J]. Aging and Disease, 2018, 9(5): 880-900. DOI: 10.14336/AD.2017.1121
[15] SCHALKWIJK C G, MIYATA T. Early- and advanced non-enzymatic glycation in diabetic vascular complications: the search for therapeutics[J]. Amino Acids, 2012, 42(4):1193-1204. DOI: 10.1007/s00726-010-0779-9
[16] BYUN K, YOO Y C, SON M, et al. Advanced glycation end-products produced systemically and by macrophages: A common contributor to inflammation and degenerative diseases[J]. Pharmacology and Therapeutics, 2017, 177: 44-55. DOI: 10.1016/j. pharmthera.2017.02.030
[17] DIL F A, RANJKESH Z, GOODARZI M T. A systematic review of antiglycation medicinal plants[J]. Diabetes and Metabolic Syndrome Clinical Research and Reviews, 2019,13(2): 1225-1229. DOI: 10.1016/j.dsx.2019.01.053
[18] YAN Shifang, RAMASAMY R, SCHMIDT A M. Receptor for AGE (RAGE) and its ligands – cast into leading roles in diabetes and the inflammatory response[J]. Journal of Molecular Medicine, 2009, 87(3): 235-247. DOI: 10.1007/s00109-009-0439-2
[19] GARAY-SEVILLA M.E, GOMEZ-OJEDA A, GONZáLEZ I, et al. Contribution of RAGE axis activation to the association between metabolic syndrome and cancer[J]. Molecular and Cellular Biochemistry, 2021, 476: 1555-1573. DOI: 10.1007/s11010-020-04022-z
[20] XIE Jianling, MéNDEZJ D, VERNA M V, et al. Cellular signalling of the receptor for advanced glycation end products (RAGE)[J]. Cellular Signalling, 2013, 25(11): 2185-2197. DOI: 10.1016/j.cellsig.2013.06.013
[21] JIN Xian, YAO Tongqing, ZHOU Zhong’e, et al. Advanced glycation end products enhance macrophages polarization into M1 phenotype through activating RAGE/NF-κB pathway[J]. Biomed Research International, 2015, 2015: 12. DOI: 10.1155/2015/732450
[22] OECKINGHAUS A, HAYDEN M, GHOSH S. Crosstalk in NF-κB signaling pathways[J]. Nature Immunology, 2011, 12(8): 695-708. DOI: 10.1038/ni.2065
[23] YU Ting, ZHENG Yongping, WANG Yun, et al. Advanced glycation end products interfere with gastric smooth muscle contractile marker expression via the AGE/RAGE/NF-κB pathway[J]. Experimental and Molecular Pathology, 2017, 102(1): 7-14. DOI: 10.1016/j.yexmp.2016.12.002
[24] ZHOU Qian, XU Hui, YU Wenzhe, et al. Anti-inflammatory effect of an apigenin-maillard reaction product in macrophages and macrophage-endothelial cocultures[J]. Oxidative Medicine and Cellular Longevity, 2019, 2019: 1-12. DOI: 10.1155/2019/9026456
[25] HUANG Pengyu, HAN Jiahuai, HUI Lijian. MAPK signaling in inflammation-associated cancer development[J]. Protein and Cell, 2010, 1(3): 218-226. DOI: 10.1007/s13238-010-0019-9
[26] YEH C H, STURGIS L, HAIDACHER J, et al. Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-κB transcriptional activation and cytokine secretion[J]. Diabetes, 2001, 50(6): 1495-1504. DOI: 10.2337/diabetes.50. 6.1495
[27] CALDER P C, AHLUWALIA N, BROUNS F, et al. Dietary factors and low-grade inflammation in relation to overweight and obesity[J]. British Journal of Nutrition, 2011, 106(3): 5-78. DOI: 10.1017 / S0007114511005460
[28] FUKAMI K, YAMAGISHI S I, OKUDA S. Role of AGEs-RAGE system in cardiovascular disease[J]. Current Pharmaceutical Design, 2013, 20(14). DOI: 10.2174/13816128113199990475
[29] BASTA G, SCHMIDT A M, CATERINA R D. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes[J]. Cardiovascular Research, 2004, 63(4): 582-592. DOI: 10.1016/j.cardiores.2004.05.001
[30] RAY P D, HUANG Bowen, TSUJI Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling[J]. Cellular Signalling, 2012, 24(5): 981-990. DOI: 10.1016/j.cellsig.2012.01.008
[31] BIERHAUS A, NAWROTH P P. Multiple levels of regulation determine the role of the receptor for AGE (RAGE) as common soil in inflammation, immune responses and diabetes mellitus and its complications[J]. Diabetologia, 2009, 52(11): 2251-2263. DOI: 10.1007/s00125-009-1458-9
[32] YAMAGISHI S I, MATSUI T, et al. Role of hyperglycemia-induced advanced glycation end product (AGE) accumulation in atherosclerosis[J]. Annals of vascular diseases, 2018, 11(3): 253-258. DOI: 10.3400/avd.ra.18-00070
[33] ANWAR S, KHAN S, ALMATROUDI A, et al. A review on mechanism of inhibition of advanced glycation end products formation by plant derived polyphenolic compounds[J]. Molecular Biology Reports, 2021, 48 (2): 1-19. DOI: 10.1007/s11033-020-06084-0
[34] SORO-PAAVONEN A, ZHANG Weizeng, VENARDOS K, et al. Advanced glycation end-products induce vascular dysfunction via resistance to nitric oxide and suppression of endothelial nitric oxide synthase[J]. Journal of Hypertension, 2010, 28(4): 780-788. DOI: 10.1097/HJH.0b013e328335043e
[35] ANDO R, UEDA S, YAMAGISHI S I, et al. Involvement of advanced glycation end product-induced asymmetric dimethylarginine generation in endothelial dysfunction[J]. Diabetes and Vascular Disease Research, 2013, 10(5): 436-441. DOI: 10.1177/1479164 113486662
[36] YAMAGISHI S I, NAKAMURA N, SUEMATSU M, et al. Advanced glycation end products: a molecular target for vascular complications in diabetes[J]. Molecular Medicine, 2015, 21: 32-40. DOI: 10.2119/molmed.2015.00067
[37] ARAúJO F F D, FARIAS D D P, NERI-NUMA I A, et al. Polyphenols and their applications: An approach in food chemistry and innovation potential[J]. Food Chemistry, 2021, 338: 127535. DOI: 10.1016/j.foodchem.2020.127535
[38] FRAGA C G, CROFT K D, KENNEDY D O, et al. The effects of polyphenols and other bioactives on human health[J]. Food and Function, 2019, 2(10): 514-528. DOI: 10.1039/c8fo01997e
[39] FRAGA C G, OTEIZA P I, GALLEANO M. Plant bioactives and redox signaling: (-)-Epicatechin as a paradigm[J]. Molecular Aspects of Medicine, 2018, 61: 31-40. DOI: 10.1016/j.mam.2018.01.007
[40] LI Wei, MALONEY R E, CIRCU M L, et al. Acute carbonyl stress induces occludin glycation and brain microvascular endothelial barrier dysfunction: Role for glutathione-dependent metabolism of methylglyoxal[J]. Free Radical Biology and Medicine, 2013, 54: 51-61. DOI: 10.1016/j.freeradbiomed.2012.10.552
[41] CHANDLER D, WOLDU A, RAHMADI A, et al. Effects of plant-derived polyphenols on TNF-alpha and nitric oxide production induced by advanced glycation end products[J]. Molecular Nutrition and Food Research, 2010, 54(2): 141-150. DOI: 10.1002/mnfr. 200900504
[42] ZHOU Qian, CHENG Kawing, GONG Jun, et al. Apigenin and its methylglyoxal-adduct inhibit advanced glycation end products-induced oxidative stress and inflammation in endothelial cells[J]. Biochemical Pharmacology, 2019, 166: 231-241. DOI: 10.1016/j. bcp.2019.05.027
[43] HASHEMZAEI M, TABRIZIAN K, ALIZADEH Z, et al. Resveratrol, curcumin and gallic acid attenuate glyoxal-induced damage to rat renal cells[J]. Toxicology Reports, 2020, 7: 1571-1577. DOI: 10.1016/j.toxrep.2020.11.008
[44] ?ZTüRK E, ARSLAN A K K, YERER M B, et al. Resveratrol and diabetes: A critical review of clinical studies[J]. Biomedicine and Pharmacotherapy, 2017, 95: 230-234. DOI: 10.1016/j.biopha.2017.08.070
[45] LIU Fengcheng, HUNG Lifeng, WU Wanlin, et al. Chondroprotective effects and mechanisms of resveratrol in advanced glycation end products-stimulated chondrocytes[J]. Arthritis Research and Therapy, 2010, 12(5): 167. DOI: 10.1186/ar3127
[46] YI C O, JEON B T, SHIN H J, et al. Resveratrol activates AMPK and suppresses LPS-induced NF-κB-dependent COX-2 activation in RAW 264.7 macrophage cells[J]. Anatomy and Cell Biology, 2011, 44(3): 194-203. DOI: 10.5115/acb.2011.44.3.194
[47] MALEKI V, FOROUMANDI E, HAJIZADEH-SHARAFABAD F, et al. The effect of resveratrol on advanced glycation end products in diabetes mellitus: a systematic review[J]. Archives of Physiology and Biochemistry, 2020, 7: 1-8. DOI: 10.1080/13813455.2019. 1673434
[48] LIN Jianguo, TANG Youcai, KANG Qiaohua, et al. Curcumin inhibits gene expression of receptor for advanced glycation end-products (RAGE) in hepatic stellate cells in vitro by elevating PPARγ activity and attenuating oxidative stress[J]. British Journal of Pharmacology, 2012, 166(8): 2212-2227. DOI: 10.1111/j.1476-5381.2012.01910.x
[49] SUN Yuping, GU Jianfeng, TAN Xiaobin, et al. Curcumin inhibits advanced glycation end productinduced oxidative stress and inflammatory responses inendothelial cell damage via trapping methylglyoxal[J]. Molecular Medicine Reports, 2016, 13(2): 1475-1486. DOI: 10.3892/mmr.2015.4725
[50] HU Teyu, LIU Chengling, CHYAU C C, et al. Trapping of methylglyoxal by curcumin in cell-free systems and in human umbilical vein endothelial cells[J]. Journal of Agricultural and Food Chemistry, 2012, 60(33): 8190-8196. DOI: 10.1021/jf302188a
[51] LEE S J, LEE K W. Protective effect of (-)-epigallocatechin gallate against advanced glycation endproducts-induced injury in neuronal cells[J]. Biological and Pharmaceutical Bulletin, 2007, 30(8): 1369-1373. DOI: 10.1248/bpb.30.1369
[52] RASHEED Z, ANBAZHAGAN A N, AKHTAR N, et al. Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-α and matrix metalloproteinase-13 in human chondrocytes[J]. Arthritis Research and Therapy, 2009, 11(3): R71. DOI: 10.1186/ar2700
[53] KIM J M, LEE E K, KIM D H, et al. Kaempferol modulates pro-inflammatory NF-κB activation by suppressing advanced glycation endproducts-induced NADPH oxidase[J]. Age, 2010, 32(2): 197-208. DOI: 10.1007/s11357-009-9124-1
[54] TENG Jing, LI Yunlong, YU Wenzhe, et al. Naringenin, a common flavanone, inhibits the formation of AGEs in bread and attenuates AGEs-induced oxidative stress and inflammation in RAW264.7 cells[J]. Food Chemistry, 2018, 269(15): 35-42. DOI: 10.1016/j. foodchem.2018.06.126
[55] ZHU Dina, WANG Lei, ZHOU Qile, et al. (+)-Catechin ameliorates diabetic nephropathy by trapping methylglyoxal in type 2 diabetic mice[J]. Molecular Nutrition and Food Research, 2014, 58(12): 2249-2260. DOI: 10.1002/mnfr.201400533
[56] MARUF A A, LIP Y H, WONG H, et al. Protective effects of ferulic acid and related polyphenols against glyoxal- or methylglyoxal-induced cytotoxicity and oxidative stress in isolated rat hepatocytes[J]. Chemico-Biological Interactions, 2015, 234: 96-104. DOI: 10.1016/j.cbi.2014.11.007
[57] CRASCì L, LAURO M R, PUGLISI G, et al. Natural antioxidant polyphenols on inflammation management: Anti-glycation activity vs metalloproteinases inhibition[J]. Critical Reviews in Food Science and Nutrition, 2018, 58(6): 893-904. DOI: 10.1080/10408398. 2016.1229657
[58] SCODITTI E, CALABRISO N, MASSARO M, et al. Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: a potentially protective mechanism in atherosclerotic vascular disease and cancer[J]. Archives of Biochemistry and Biophysics, 2012, 527(2): 81-89. DOI: 10.1016/j.abb.2012.05.003
[59] UMADEVI S, GOPI V, ELANGOVAN V. Regulatory mechanism of gallic acid against advanced glycation end products induced cardiac remodeling in experimental rats[J]. Chemico-Biological Interactions, 2014, 208: 28-36. DOI: 10.1016/j.cbi.2013.11.013
[60] OHTSU A, SHIBUTANI Y, SENO K, et al. Advanced glycation end products and lipopolysaccharides stimulate interleukin-6 secretion via the RAGE/TLR4-NF-κB-ROS pathways and resveratrol attenuates these inflammatory responses in mouse macrophages[J]. Experimental and Therapeutic Medicine, 2017, 14(5): 4363-4370. DOI: 10.3892/etm.2017.5045
[61] WANG Shuxia, CAO Meng, XU Shuhang, et al. Effect of luteolin on inflammatory responses in RAW264.7 macrophages activated with LPS and IFN-γ[J]. Journal of Functional Foods, 2017, 32: 123-130. DOI: 10.1016/j.jff.2017.02.018
[62] FERNANDES A C F, VIEIRA N C, SANTANA á L D, et al. Peanut skin polyphenols inhibit toxicity induced by advanced glycation end-products in RAW264.7 macrophages[J]. Food and Chemical Toxicology, 2020, 145: 111619. DOI: 10.1016/j.fct.2020.111619
[63] ZHANG Xiaoyi, SONG Yu, HAN Xiaolin, et al. Liquiritin attenuates advanced glycation end products-induced endothelial dysfunction via RAGE/NF-κB pathway in human umbilical vein endothelial cells[J]. Molecular and Cellular Biochemistry, 2013, 374: 191-201. DOI: 10.1007/s11010-012-1519-0