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Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

Role of Polyphenol in Regulating Oxidative Stress, Inflammation, Fibrosis, and Apoptosis in Diabetic Nephropathy

Author(s): Syaifuzah Sapian*, Siti Balkis Budin, Izatus Shima Taib, Vanitha Mariappan, Satirah Zainalabidin and Kok Yong Chin

Volume 22, Issue 5, 2022

Published on: 03 February, 2022

Page: [453 - 470] Pages: 18

DOI: 10.2174/1871530321666211119144309

Price: $65


Diabetic Nephropathy (DN) is known as one of the driving sources of End-Stage Renal Disease (ESRD). DN prevalence continues to increase in every corner of the world andthat has been a major concern to healthcare professionals as DN is the key driver of Diabetes Mellitus (DM) morbidity and mortality. Hyperglycaemia is closely connected with the production of Reactive Oxygen Species (ROS) that cause oxidative stress response as well as numerous cellular and molecular modifications. Oxidative stress is a significant causative factor to renal damage, as it can activate other immunological pathways, such as inflammatory, fibrosis, and apoptosis pathways. These pathways can lead to cellular impairment and death as well as cellular senescence. Natural substances containing bioactive compounds, such as polyphenols, have been reported to exert valuable effects on various pathological conditions, including DM. The role of polyphenols in alleviating DN conditions has been documented in many studies. In this review, the potential of polyphenols in ameliorating the progression of DN via modulation of oxidative stress, inflammation, fibrosis, and apoptosis, as well as cellular senescence, has been addressed. This information may be used as the strategies for the management of DN and development as nutraceutical products to overcome DN development.

Keywords: Diabetes mellitus, diabetic nephropathy, reactive oxygen species, phytochemicals, bioactive compounds, fibrosis.

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(NCD-RisC) NRFC. Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants. Lancet, 2016, 2016, 6.
(IDF) IDF. Diabetes facts & figures. 2019. Available from:
Asmat, U.; Abad, K.; Ismail, K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm. J., 2016, 24(5), 547-553.
[] [PMID: 27752226]
Umanath, K.; Lewis, J.B. Update on diabetic nephropathy: core curriculum 2018. Am. J. Kidney Dis., 2018, 71(6), 884-895.
[] [PMID: 29398179]
Al-Waili, N.; Al-Waili, H.; Al-Waili, T.; Salom, K. Natural antioxidants in the treatment and prevention of diabetic nephropathy; a potential approach that warrants clinical trials. Redox Rep., 2017, 22(3), 99-118.
[] [PMID: 28276289]
Fornoni, A.; Ijaz, A.; Tejada, T.; Lenz, O. Role of inflammation in diabetic nephropathy. Curr. Diabetes Rev., 2008, 4(1), 10-17.
[] [PMID: 18220690]
Zeng, L-F; Xiao, Y; Sun, L A glimpse of the mechanisms related to renal fibrosis in diabetic nephropathy. Renal Fibrosis: Mechanisms Therap., 2019, 49-79.
Chmelová, D.; Škulcová, D.; Legerská, B.; Horník, M.; Ondrejovič, M. Ultrasonic-assisted extraction of polyphenols and antioxidants from Picea abies bark. J. Biotechnol., 2020, 314-315, 25-33.
[] [PMID: 32294516]
Sharma, K. Mitochondrial hormesis and diabetic complications. Diabetes, 2015, 64(3), 663-672.
[] [PMID: 25713188]
Cory, H.; Passarelli, S.; Szeto, J.; Tamez, M.; Mattei, J. The role of polyphenols in human health and food systems: A mini-review. Front. Nutr., 2018, 5, 87.
[] [PMID: 30298133]
Giacco, F.; Brownlee, M. Oxidative stress and diabetic complications. Circ. Res., 2010, 107(9), 1058-1070.
[] [PMID: 21030723]
Grosso, G.; Stepaniak, U.; Topor-Mądry, R.; Szafraniec, K.; Pająk, A. Estimated dietary intake and major food sources of polyphenols in the Polish arm of the HAPIEE study. Nutrition, 2014, 30(11-12), 1398-1403.
[] [PMID: 25280419]
Hayashi, D.; Wang, L.; Ueda, S.; Yamanoue, M.; Ashida, H.; Shirai, Y. The mechanisms of ameliorating effect of a green tea polyphenol on diabetic nephropathy based on diacylglycerol kinase α. Sci. Rep., 2020, 10(1), 11790.
[] [PMID: 32678222]
Zhen, J.; Villani, T.S.; Guo, Y.; Qi, Y.; Chin, K.; Pan, M-H.; Ho, C.T.; Simon, J.E.; Wu, Q. Phytochemistry, antioxidant capacity, total phenolic content and anti-inflammatory activity of Hibiscus sabdariffa leaves. Food Chem., 2016, 190, 673-680.
[] [PMID: 26213025]
Sifuentes-Franco, S.; Padilla-Tejeda, D.E.; Carrillo-Ibarra, S.; Miranda-Díaz, A.G. Oxidative stress, apoptosis, and mitochondrial function in diabetic nephropathy. Int. J. Endocrinol., 2018, 2018, 1875870.
[] [PMID: 29808088]
Wang, X.; Li, J.; Huo, L.; Feng, Y.; Ren, L.; Yao, X.; Jiang, H.; Lv, R.; Zhu, M.; Chen, J. Clinical characteristics of diabetic nephropathy in patients with type 2 diabetic mellitus manifesting heavy proteinuria: A retrospective analysis of 220 cases. Diabetes Res. Clin. Pract., 2019, 157, 107874.
[] [PMID: 31593744]
Said, S.M.; Nasr, S.H. Silent diabetic nephropathy. Kidney Int., 2016, 90(1), 24-26.
[] [PMID: 27312444]
Al Hroob, A.M.; Abukhalil, M.H.; Alghonmeen, R.D.; Mahmoud, A.M. Ginger alleviates hyperglycemia-induced oxidative stress, inflammation and apoptosis and protects rats against diabetic nephropathy. Biomed. Pharmacother., 2018, 106, 381-389.
[] [PMID: 29966984]
Ling, X.C.; Kuo, K-L. Oxidative stress in chronic kidney disease. Renal Replacement Ther.., 2018, 4(1), 53.
Forbes, J.M.; Thallas, V.; Thomas, M.C.; Founds, H.W.; Burns, W.C.; Jerums, G.; Cooper, M.E. The breakdown of preexisting advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. FASEB J., 2003, 17(12), 1762-1764.
[] [PMID: 12958202]
Podkowińska, A.; Formanowicz, D. Chronic kidney disease as oxidative stress- and inflammatory-mediated cardiovascular disease. Antioxidants, 2020, 9(8), E752.
[] [PMID: 32823917]
Vodošek Hojs, N.; Bevc, S.; Ekart, R.; Hojs, R. Oxidative stress markers in chronic kidney disease with emphasis on diabetic nephropathy. Antioxidants, 2020, 9(10), E925.
[] [PMID: 32992565]
Fakhruddin, S.; Alanazi, W.; Jackson, K.E. Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury. J. Diabetes Res., 2017, 2017, 8379327.
[] [PMID: 28164134]
Miranda-Díaz, AG; Pazarín-Villaseñor, L; Yanowsky-Escatell, FG; Andrade-Sierra, J Oxidative stress in diabetic nephropathy with early chronic kidney disease. J. Diabetes Res., 2016, 2016
Manda, G.; Checherita, A-I.; Comanescu, M.V.; Hinescu, M.E. Redox signaling in diabetic nephropathy: Hypertrophy versus death choices in mesangial cells and podocytes. Mediators Inflamm., 2015, 2015, 604208.
[] [PMID: 26491232]
Das, J.; Sil, P.C. Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats. Amino Acids, 2012, 43(4), 1509-1523.
[] [PMID: 22302365]
Kachhawa, K.; Agrawal, D.; Rath, B.; Kumar, S. Association of lipid abnormalities and oxidative stress with diabetic nephropathy. J. Integr. Nephrol. Androl., 2017, 4(1), 3-9.
Pieper, G.M.; Riaz-ul-Haq, Activation of nuclear factor-kappaB in cultured endothelial cells by increased glucose concentration: prevention by calphostin C. J. Cardiovasc. Pharmacol., 1997, 30(4), 528-532.
[] [PMID: 9335415]
Koya, D.; Jirousek, M.R.; Lin, Y-W.; Ishii, H.; Kuboki, K.; King, G.L. Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats. J. Clin. Invest., 1997, 100(1), 115-126.
[] [PMID: 9202063]
Manda, G; Checherita, A-I; Comanescu, MV; Hinescu, ME Redox signaling in diabetic nephropathy: hypertrophy versus death choices in mesangial cells and podocytes. Mediators Inflammation., 2015, 604208.
Horie, K.; Miyata, T.; Maeda, K.; Miyata, S.; Sugiyama, S.; Sakai, H.; van Ypersole de Strihou, C.; Monnier, V.M.; Witztum, J.L.; Kurokawa, K. Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions. Implication for glycoxidative stress in the pathogenesis of diabetic nephropathy. J. Clin. Invest., 1997, 100(12), 2995-3004.
[] [PMID: 9399945]
Wells-Knecht, K.J.; Zyzak, D.V.; Litchfield, J.E.; Thorpe, S.R.; Baynes, J.W. Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose. Biochemistry, 1995, 34(11), 3702-3709.
[] [PMID: 7893666]
Routledge, M.N.; Wink, D.A.; Keefer, L.K.; Dipple, A. DNA sequence changes induced by two nitric oxide donor drugs in the supF assay. Chem. Res. Toxicol., 1994, 7(5), 628-632.
[] [PMID: 7841341]
Thornalley, P.J. The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life. Biochem. J., 1990, 269(1), 1-11.
[] [PMID: 2198020]
Studer, R.K.; Craven, P.A.; DeRubertis, F.R. Role for protein kinase C in the mediation of increased fibronectin accumulation by mesangial cells grown in high-glucose medium. Diabetes, 1993, 42(1), 118-126.
[] [PMID: 8420808]
Kasiske, B.L. Hyperlipidemia in patients with chronic renal disease. Am. J. Kidney Dis., 1998, 32(5)(Suppl. 3), S142-S156.
[] [PMID: 9820472]
Manda, G; Checherita, A-I; Comanescu, MV; Hinescu, ME Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes. 2015, 604208.
Ahmad, P.; Jaleel, C.; Sharma, S. Antioxidant defense system, lipid peroxidation, proline-metabolizing enzymes, and biochemical activities in two Morus alba genotypes subjected to NaCl stress. Russ. J. Plant Physiol., 2010, 57(4), 509-517.
Figueroa-Romero, C.; Sadidi, M.; Feldman, E.L. Mechanisms of disease: the oxidative stress theory of diabetic neuropathy. Rev. Endocr. Metab. Disord., 2008, 9(4), 301-314.
[] [PMID: 18709457]
Perlman, A.S.; Chevalier, J.M.; Wilkinson, P.; Liu, H.; Parker, T.; Levine, D.M.; Sloan, B.J.; Gong, A.; Sherman, R.; Farrell, F.X. Serum inflammatory and immune mediators are elevated in early stage diabetic nephropathy. Ann. Clin. Lab. Sci., 2015, 45(3), 256-263.
[PMID: 26116588]
Kanwar, Y.S.; Sun, L.; Xie, P.; Liu, F.Y.; Chen, S. A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu. Rev. Pathol., 2011, 6, 395-423.
[] [PMID: 21261520]
Li, Y.; Liu, J.; Liao, G.; Zhang, J.; Chen, Y.; Li, L.; Li, L.; Liu, F.; Chen, B.; Guo, G.; Wang, C.; Yang, L.; Cheng, J.; Lu, Y. Early intervention with mesenchymal stem cells prevents nephropathy in diabetic rats by ameliorating the inflammatory microenvironment. Int. J. Mol. Med., 2018, 41(5), 2629-2639.
[] [PMID: 29484379]
Duran-Salgado, M.B.; Rubio-Guerra, A.F. Diabetic nephropathy and inflammation. World J. Diabetes, 2014, 5(3), 393-398.
[] [PMID: 24936261]
Hu, N.; Duan, J.; Li, H.; Wang, Y.; Wang, F.; Chu, J.; Sun, J.; Liu, M.; Wang, C.; Lu, C.; Wen, A. Hydroxysafflor yellow a ameliorates renal fibrosis by suppressing TGF-β1-induced epithelial-to-mesenchymal transition. PLoS One, 2016, 11(4), e0153409.
[] [PMID: 27088510]
Salti, T.; Khazim, K.; Haddad, R.; Campisi-Pinto, S.; Bar-Sela, G.; Cohen, I. Glucose induces il-1α-dependent inflammation and extracellular matrix proteins expression and deposition in renal tubular epithelial cells in diabetic kidney disease. Front. Immunol., 2020, 11(1270), 1270.
[] [PMID: 32733443]
Gewin, L.S. Renal tubule repair: is Wnt/β-catenin a friend or foe? Genes (Basel), 2018, 9(2), 58.
[] [PMID: 29364168]
Srinivasan, S.; Stevens, M.; Wiley, J.W. Diabetic peripheral neuropathy: evidence for apoptosis and associated mitochondrial dysfunction. Diabetes, 2000, 49(11), 1932-1938.
[] [PMID: 11078462]
Kesavardhana, S.; Malireddi, R.K.S.; Kanneganti, T-D. Caspases in cell death, inflammation, and pyroptosis. Annu. Rev. Immunol., 2020, 38, 567-595.
[] [PMID: 32017655]
Jin, J.; Shi, Y.; Gong, J.; Zhao, L.; Li, Y.; He, Q.; Huang, H. Exosome secreted from adipose-derived stem cells attenuates diabetic nephropathy by promoting autophagy flux and inhibiting apoptosis in podocyte. Stem Cell Res. Ther., 2019, 10(1), 95.
[] [PMID: 30876481]
Kumar, D.; Robertson, S.; Burns, K.D. Evidence of apoptosis in human diabetic kidney. Mol. Cell. Biochem., 2004, 259(1-2), 67-70.
[] [PMID: 15124909]
Perkins, G.; Bossy-Wetzel, E.; Ellisman, M.H. New insights into mitochondrial structure during cell death. Exp. Neurol., 2009, 218(2), 183-192.
[] [PMID: 19464290]
Sprick, M.R.; Weigand, M.A.; Rieser, E.; Rauch, C.T.; Juo, P.; Blenis, J.; Krammer, P.H.; Walczak, H. FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity, 2000, 12(6), 599-609.
[] [PMID: 10894160]
Li, H.; Zhu, H.; Xu, C.J.; Yuan, J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell, 1998, 94(4), 491-501.
[] [PMID: 9727492]
Zou, H.; Henzel, W.J.; Liu, X.; Lutschg, A.; Wang, X. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell, 1997, 90(3), 405-413.
[] [PMID: 9267021]
Abbas, M.; Saeed, F.; Anjum, F.M.; Afzaal, M.; Tufail, T.; Bashir, M.S. Natural polyphenols: An overview. Int. J. Food Prop., 2017, 20(8), 1689-1699.
Lazavi, F.; Mirmiran, P.; Sohrab, G.; Nikpayam, O.; Angoorani, P.; Hedayati, M. The barberry juice effects on metabolic factors and oxidative stress in patients with type 2 diabetes: A randomized clinical trial. Complement. Ther. Clin. Pract., 2018, 31, 170-174.
[] [PMID: 29705451]
Mahmoud, A.M.; Abd El-Twab, S.M.; Abdel-Reheim, E.S. Consumption of polyphenol-rich Morus alba leaves extract attenuates early diabetic retinopathy: the underlying mechanism. Eur. J. Nutr., 2017, 56(4), 1671-1684.
[] [PMID: 27059477]
Sattarinezhad, A.; Roozbeh, J.; Shirazi Yeganeh, B.; Omrani, G.R.; Shams, M. Resveratrol reduces albuminuria in diabetic nephropathy: A randomized double-blind placebo-controlled clinical trial. Diabetes Metab., 2019, 45(1), 53-59.
[] [PMID: 29983230]
Liu, H-W.; Chang, S-J. Moderate exercise suppresses NF-κB signaling and activates the SIRT1-AMPK-PGC1α axis to attenuate muscle loss in diabetic db/db mice. Front. Physiol., 2018, 9, 636.
[] [PMID: 29896118]
Justino, A.B.; Pereira, M.N.; Peixoto, L.G.; Vilela, D.D.; Caixeta, D.C.; de Souza, A.V.; Teixeira, R.R.; Silva, H.C.G.; de Moura, F.B.R.; Moraes, I.B.; Espindola, F.S. Hepatoprotective properties of a polyphenol-enriched fraction from Annona crassiflora Mart. fruit peel against diabetes-induced oxidative and nitrosative stress. J. Agric. Food Chem., 2017, 65(22), 4428-4438.
[] [PMID: 28514152]
Sedlak, L.; Wojnar, W.; Zych, M.; Wyględowska-Promieńska, D.; Mrukwa-Kominek, E.; Kaczmarczyk-Sedlak, I. Effect of resveratrol, a dietary-derived polyphenol, on the oxidative stress and polyol pathway in the lens of rats with streptozotocin-induced diabetes. Nutrients, 2018, 10(10), 1423.
[] [PMID: 30287729]
Olatunji, O.J.; Chen, H.; Zhou, Y. Effect of the polyphenol rich ethyl acetate fraction from the leaves of Lycium chinensemill. on oxidative stress, dyslipidemia, and diabetes mellitus in streptozotocin-nicotinamide induced diabetic rats. Chem. Biodivers., 2017, 14(10), e1700277.
[] [PMID: 28677319]
Mohammed Yusof, N.L.; Zainalabidin, S.; Mohd Fauzi, N.; Budin, S.B. Hibiscus sabdariffa (roselle) polyphenol-rich extract averts cardiac functional and structural abnormalities in type 1 diabetic rats. Appl. Physiol. Nutr. Metab., 2018, 43(12), 1224-1232.
[] [PMID: 29726706]
Budin, S.B.; Rahman, W.Z.A.; Jubaidi, F.F.; Yusof, N.L.M.; Taib, I.S.; Zainalabidin, S. Roselle (Hibiscus sabdiriffa) polyphenol-rich extract prevents testicular damage of diabetic rats. J. Appl. Pharm. Sci., 2018, 8(2), 65-70.
Huang, C-N.; Wang, C-J.; Yang, Y-S.; Lin, C-L.; Peng, C-H. Hibiscus sabdariffa polyphenols prevent palmitate-induced renal epithelial mesenchymal transition by alleviating dipeptidyl peptidase-4-mediated insulin resistance. Food Funct., 2016, 7(1), 475-482.
[] [PMID: 26514092]
Gojkovic-Bukarica, L.; Markovic-Lipkovski, J.; Heinle, H.; Cirovic, S.; Rajkovic, J.; Djokic, V. The red wine polyphenol resveratrol induced relaxation of the isolated renal artery of diabetic rats: The role of potassium channels. J. Funct. Foods, 2019, 52, 266-275.
Yuan, Y.; Zheng, Y.; Zhou, J.; Geng, Y.; Zou, P.; Li, Y.; Zhang, C. Polyphenol-rich extracts from Brown Macroalgae Lessonia trabeculate attenuate hyperglycemia and modulate gut microbiota in high-fat diet and streptozotocin-induced diabetic rats. J. Agric. Food Chem., 2019, 67(45), 12472-12480.
[] [PMID: 31642672]
Doan, K.V.; Ko, C.M.; Kinyua, A.W.; Yang, D.J.; Choi, Y-H.; Oh, I.Y.; Nguyen, N.M.; Ko, A.; Choi, J.W.; Jeong, Y.; Jung, M.H.; Cho, W.G.; Xu, S.; Park, K.S.; Park, W.J.; Choi, S.Y.; Kim, H.S.; Moh, S.H.; Kim, K.W. Gallic acid regulates body weight and glucose homeostasis through AMPK activation. Endocrinology, 2015, 156(1), 157-168.
[] [PMID: 25356824]
Park, C.H.; Noh, J.S.; Fujii, H.; Roh, S.S.; Song, Y.O.; Choi, J.S.; Chung, H.Y.; Yokozawa, T. Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, attenuates gluco-lipotoxicity-mediated renal disorder in type 2 diabetic db/db mice. Drug Discov. Ther., 2015, 9(1), 13-22.
[] [PMID: 25788048]
Zhou, B.; Li, Q.; Wang, J.; Chen, P.; Jiang, S. Ellagic acid attenuates streptozocin induced diabetic nephropathy via the regulation of oxidative stress and inflammatory signaling. Food Chem. Toxicol., 2019, 123, 16-27.
[] [PMID: 30342113]
Álvarez-Cilleros, D.; López-Oliva, M.E.; Martín, M.Á.; Ramos, S. Cocoa ameliorates renal injury in Zucker diabetic fatty rats by preventing oxidative stress, apoptosis and inactivation of autophagy. Food Funct., 2019, 10(12), 7926-7939.
[] [PMID: 31773121]
Bao, L.; Li, J.; Zha, D.; Zhang, L.; Gao, P.; Yao, T.; Wu, X. Chlorogenic acid prevents diabetic nephropathy by inhibiting oxidative stress and inflammation through modulation of the Nrf2/HO-1 and NF-ĸB pathways. Int. Immunopharmacol., 2018, 54, 245-253.
[] [PMID: 29161661]
Palanisamy, N.; Venkataraman, A.C. Beneficial effect of genistein on lowering blood pressure and kidney toxicity in fructose-fed hypertensive rats. Br. J. Nutr., 2013, 109(10), 1806-1812.
[] [PMID: 23116847]
Mou, Z.; Feng, Z.; Xu, Z.; Zhuang, F.; Zheng, X.; Li, X.; Qian, J.; Liang, G. Schisandrin B alleviates diabetic nephropathy through suppressing excessive inflammation and oxidative stress. Biochem. Biophys. Res. Commun., 2019, 508(1), 243-249.
[] [PMID: 30477745]
Wang, X.; Li, D.; Fan, L.; Xiao, Q.; Zuo, H.; Li, Z. CAPE-pNO2 ameliorated diabetic nephropathy through regulating the Akt/NF-κB/ iNOS pathway in STZ-induced diabetic mice. Oncotarget, 2017, 8(70), 114506-114525.
[] [PMID: 29383098]
Borgohain, M.P.; Lahkar, M.; Ahmed, S.; Chowdhury, L.; Kumar, S.; Pant, R.; Choubey, A. Small molecule inhibiting nuclear factor-kb ameliorates oxidative stress and suppresses renal inflammation in early stage of alloxan-induced diabetic nephropathy in rat. Basic Clin. Pharmacol. Toxicol., 2017, 120(5), 442-449.
[] [PMID: 27888584]
Yoon, J.J.; Lee, H.K.; Kim, H.Y.; Han, B.H.; Lee, H.S.; Lee, Y.J.; Kang, D.G. Sauchinone protects renal mesangial cell dysfunction against angiotensin ii by improving renal fibrosis and inflammation. Int. J. Mol. Sci., 2020, 21(19), E7003.
[] [PMID: 32977573]
Gandhi, G.R.; Jothi, G.; Antony, P.J.; Balakrishna, K.; Paulraj, M.G.; Ignacimuthu, S.; Stalin, A.; Al-Dhabi, N.A. Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARγ in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway. Eur. J. Pharmacol., 2014, 745, 201-216.
[] [PMID: 25445038]
Abouzed, T.K.; Sadek, K.M.; Ghazy, E.W.; Abdo, W.; Kassab, M.A.; Hago, S.; Abdel-Wahab, S.; Mahrous, E.A.; Abdel-Sattar, E.; Assar, D.H. Black mulberry fruit extract alleviates streptozotocin-induced diabetic nephropathy in rats: targeting TNF-α inflammatory pathway. J. Pharm. Pharmacol., 2020, 72(11), 1615-1628.
[] [PMID: 32754951]
Qi, M.Y.; Wang, X.T.; Xu, H.L.; Yang, Z.L.; Cheng, Y.; Zhou, B. Protective effect of ferulic acid on STZ-induced diabetic nephropathy in rats. Food Funct., 2020, 11(4), 3706-3718.
[] [PMID: 32307498]
Shukla, R.; Banerjee, S.; Tripathi, Y.B. Antioxidant and Antiapoptotic effect of aqueous extract of Pueraria tuberosa (Roxb. Ex Willd.) DC. On streptozotocin-induced diabetic nephropathy in rats. BMC Complement. Altern. Med., 2018, 18(1), 156.
[] [PMID: 29751837]
Chowdhury, S.; Ghosh, S.; Das, A.K.; Sil, P.C. Ferulic acid protects hyperglycemia-induced kidney damage by regulating oxidative insult, inflammation and autophagy. Front. Pharmacol., 2019, 10, 27.
[] [PMID: 30804780]
Hou, B.; Qiang, G.; Zhao, Y.; Yang, X.; Chen, X.; Yan, Y.; Wang, X.; Liu, C.; Zhang, L.; Du, G. Salvianolic acid A protects against diabetic nephropathy through ameliorating glomerular endothelial dysfunction via inhibiting AGE-RAGE signaling. Cell. Physiol. Biochem., 2017, 44(6), 2378-2394.
[] [PMID: 29262395]
Ahmed, S.M.U.; Luo, L.; Namani, A.; Wang, X.J.; Tang, X. Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim. Biophys. Acta Mol. Basis Dis., 2017, 1863(2), 585-597.
[] [PMID: 27825853]
Chao, C.Y.; Mong, M.C.; Chan, K.C.; Yin, M.C. Anti-glycative and anti-inflammatory effects of caffeic acid and ellagic acid in kidney of diabetic mice. Mol. Nutr. Food Res., 2010, 54(3), 388-395.
[] [PMID: 19885845]
Pal, P.B.; Sinha, K.; Sil, P.C. Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFα related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats. PLoS One, 2014, 9(9), e107220.
[] [PMID: 25233093]
Yang, W-J.; Li, Y-R.; Gao, H.; Wu, X-Y.; Wang, X-L.; Wang, X-N.; Xiang, L.; Ren, D.M.; Lou, H.X.; Shen, T. Protective effect of the ethanol extract from Ligusticum chuanxiong rhizome against streptozotocin-induced diabetic nephropathy in mice. J. Ethnopharmacol., 2018, 227, 166-175.
[] [PMID: 30176347]
Gomes, I.B.; Porto, M.L.; Santos, M.C.L.; Campagnaro, B.P.; Pereira, T.M.; Meyrelles, S.S.; Vasquez, E.C. Renoprotective, anti-oxidative and anti-apoptotic effects of oral low-dose quercetin in the C57BL/6J model of diabetic nephropathy. Lipids Health Dis., 2014, 13(1), 184.
[] [PMID: 25481305]
Ruderman, N.B.; Carling, D.; Prentki, M.; Cacicedo, J.M. AMPK, insulin resistance, and the metabolic syndrome. J. Clin. Invest., 2013, 123(7), 2764-2772.
[] [PMID: 23863634]
Koh, E.S.; Lim, J.H.; Kim, M.Y.; Chung, S.; Shin, S.J.; Choi, B.S.; Kim, H.W.; Hwang, S.Y.; Kim, S.W.; Park, C.W.; Chang, Y.S. Anthocyanin-rich Seoritae extract ameliorates renal lipotoxicity via activation of AMP-activated protein kinase in diabetic mice. J. Transl. Med., 2015, 13(1), 203.
[] [PMID: 26116070]
Wei, J.; Wu, H.; Zhang, H.; Li, F.; Chen, S.; Hou, B.; Shi, Y.; Zhao, L.; Duan, H. Anthocyanins inhibit high glucose-induced renal tubular cell apoptosis caused by oxidative stress in db/db mice. Int. J. Mol. Med., 2018, 41(3), 1608-1618.
[] [PMID: 29328429]
Yang, S.; Ma, C.; Wu, H.; Zhang, H.; Yuan, F.; Yang, G.; Yang, Q.; Jia, L.; Liang, Z.; Kang, L. Tectorigenin attenuates diabetic nephropathy by improving vascular endothelium dysfunction through activating AdipoR1/2 pathway. Pharmacol. Res., 2020, 153, 104678.
[] [PMID: 32014572]
Malik, S.; Suchal, K.; Khan, S.I.; Bhatia, J.; Kishore, K.; Dinda, A.K.; Arya, D.S. Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways. Am. J. Physiol. Renal Physiol., 2017, 313(2), F414-F422.
[] [PMID: 28566504]
Tang, Y.; Li, T.; Peng, L.; Liu, J.; Wang, Y.; Piao, C. Dose-response regulation system for improving renal injury in diabetic nephropathy by buckwheat hull flavonoids. J. Funct. Foods, 2019, 62, 103561.
Ma, Y.; Chen, F.; Yang, S.; Chen, B.; Shi, J. Protocatechuic acid ameliorates high glucose-induced extracellular matrix accumulation in diabetic nephropathy. Biomed. Pharmacother., 2018, 98, 18-22.
[] [PMID: 29241070]
Cai, X.; Bao, L.; Ren, J.; Li, Y.; Zhang, Z. Grape seed procyanidin B2 protects podocytes from high glucose-induced mitochondrial dysfunction and apoptosis via the AMPK-SIRT1-PGC-1α axis in vitro. Food Funct., 2016, 7(2), 805-815.
[] [PMID: 26650960]
Wang, S.; Fang, Y.; Yu, X.; Guo, L.; Zhang, X.; Xia, D. The flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. ameliorates renal oxidative stress and inflammation in uric acid nephropathy rats through promoting uric acid excretion. Biomed. Pharmacother., 2019, 111, 162-168.
[] [PMID: 30579255]
Omotuyi, O.I.; Nash, O.; Enejoh, O.A.; Oribamise, E.I.; Adelakun, N.S. Chromolaena odorata flavonoids attenuate experimental nephropathy: Involvement of pro-inflammatory genes downregulation. Toxicol. Rep., 2020, 7, 1421-1427.
[] [PMID: 33102146]
Vang, O.; Ahmad, N.; Baile, C.A.; Baur, J.A.; Brown, K.; Csiszar, A.; Das, D.K.; Delmas, D.; Gottfried, C.; Lin, H.Y.; Ma, Q.Y.; Mukhopadhyay, P.; Nalini, N.; Pezzuto, J.M.; Richard, T.; Shukla, Y.; Surh, Y.J.; Szekeres, T.; Szkudelski, T.; Walle, T.; Wu, J.M. What is new for an old molecule? Systematic review and recommendations on the use of resveratrol. PLoS One, 2011, 6(6), e19881.
[] [PMID: 21698226]
Moridi, H; Karimi, J; Sheikh, N; Goodarzi, MT; Saidijam, M; Yadegarazari, R Resveratrol-Dependent Down-regulation of Receptor for Advanced Glycation End-products and Oxidative Stress in Kidney of Rats With Diabetes. Int. J. Endocrinol. Metab., 2015, 13(2), e23542.
Al-Hussaini, H.; Kilarkaje, N. Trans-resveratrol mitigates type 1 diabetes-induced oxidative DNA damage and accumulation of advanced glycation end products in glomeruli and tubules of rat kidneys. Toxicol. Appl. Pharmacol., 2018, 339, 97-109.
[] [PMID: 29229234]
Ramar, M.; Manikandan, B.; Raman, T.; Priyadarsini, A.; Palanisamy, S.; Velayudam, M.; Munusamy, A.; Marimuthu Prabhu, N.; Vaseeharan, B. Protective effect of ferulic acid and resveratrol against alloxan-induced diabetes in mice. Eur. J. Pharmacol., 2012, 690(1-3), 226-235.
[] [PMID: 22659112]
Qiao, Y.; Gao, K.; Wang, Y.; Wang, X.; Cui, B. Resveratrol ameliorates diabetic nephropathy in rats through negative regulation of the p38 MAPK/TGF-β1 pathway. Exp. Ther. Med., 2017, 13(6), 3223-3230.
[] [PMID: 28588674]
Saravanan, S.; Pari, L. Protective effect of thymol on high fat diet induced diabetic nephropathy in C57BL/6J mice. Chem. Biol. Interact., 2016, 245, 1-11.
[] [PMID: 26680107]
He, T.; Xiong, J.; Nie, L.; Yu, Y.; Guan, X.; Xu, X.; Xiao, T.; Yang, K.; Liu, L.; Zhang, D.; Huang, Y.; Zhang, J.; Wang, J.; Sharma, K.; Zhao, J. Resveratrol inhibits renal interstitial fibrosis in diabetic nephropathy by regulating AMPK/NOX4/ROS pathway. J. Mol. Med. (Berl.), 2016, 94(12), 1359-1371.
[] [PMID: 27488452]
Nadeem, M.; Taj K., I.; Khan, F.; Shah, M.; Niaz, K. Lignans and flavonolignans; , 2020, pp. 98-116.
Ma, Q. Role of nrf2 in oxidative stress and toxicity. Annu. Rev. Pharmacol. Toxicol., 2013, 53, 401-426.
[] [PMID: 23294312]
Kaur, N.; Kishore, L.; Singh, R. Therapeutic effect of Linum usitatissimum L. in STZ-nicotinamide induced diabetic nephropathy via inhibition of AGE’s and oxidative stress. J. Food Sci. Technol., 2017, 54(2), 408-421.
[] [PMID: 28242940]
Zhang, J.; Cao, P.; Gui, J.; Wang, X.; Han, J.; Wang, Y.; Wang, G. Arctigenin ameliorates renal impairment and inhibits endoplasmic reticulum stress in diabetic db/db mice. Life Sci., 2019, 223, 194-201.
[] [PMID: 30898648]
Zhong, Y.; Lee, K.; Deng, Y.; Ma, Y.; Chen, Y.; Li, X.; Wei, C.; Yang, S.; Wang, T.; Wong, N.J.; Muwonge, A.N.; Azeloglu, E.U.; Zhang, W.; Das, B.; He, J.C.; Liu, R. Arctigenin attenuates diabetic kidney disease through the activation of PP2A in podocytes. Nat. Commun., 2019, 10(1), 4523.
[] [PMID: 31586053]
Niu, H-S.; Liu, I.M.; Niu, C-S.; Ku, P-M.; Hsu, C-T.; Cheng, J-T. Eucommia bark (Du-Zhong) improves diabetic nephropathy without altering blood glucose in type 1-like diabetic rats. Drug Des. Devel. Ther., 2016, 10, 971-978.
[PMID: 27041999]
Valentijn, F.A.; Falke, L.L.; Nguyen, T.Q.; Goldschmeding, R. Cellular senescence in the aging and diseased kidney. J. Cell Commun. Signal., 2018, 12(1), 69-82.
[] [PMID: 29260442]
Kitada, K.; Nakano, D.; Ohsaki, H.; Hitomi, H.; Minamino, T.; Yatabe, J.; Felder, R.A.; Mori, H.; Masaki, T.; Kobori, H.; Nishiyama, A. Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy. J. Diabetes Complications, 2014, 28(5), 604-611.
[] [PMID: 24996978]
Xiong, Y; Zhou, L The signaling of cellular senescence in diabetic nephropathy. 2019.
Zhu, K.; Kakehi, T.; Matsumoto, M.; Iwata, K.; Ibi, M.; Ohshima, Y.; Zhang, J.; Liu, J.; Wen, X.; Taye, A.; Fan, C.; Katsuyama, M.; Sharma, K.; Yabe-Nishimura, C. NADPH oxidase NOX1 is involved in activation of protein kinase C and premature senescence in early stage diabetic kidney. Free Radic. Biol. Med., 2015, 83, 21-30.
[] [PMID: 25701431]
Fang, Y.; Gong, A.Y.; Haller, S.T.; Dworkin, L.D.; Liu, Z.; Gong, R. The ageing kidney: Molecular mechanisms and clinical implications. Ageing Res. Rev., 2020, 63, 101151.
[] [PMID: 32835891]
Vaiserman, A.; Krasnienkov, D. Telomere length as a marker of biological age: state-of-the-art, open issues, and future perspectives. Front. Genet., 2021, 11, 630186.
[] [PMID: 33552142]
Luo, J.; Si, H.; Jia, Z.; Liu, D. Dietary anti-aging polyphenols and potential mechanisms. Antioxidants, 2021, 10(2), 283.
[] [PMID: 33668479]
Cao, D.; Zhao, M.; Wan, C.; Zhang, Q.; Tang, T.; Liu, J.; Shao, Q.; Yang, B.; He, J.; Jiang, C. Role of tea polyphenols in delaying hyperglycemia-induced senescence in human glomerular mesangial cells via miR-126/Akt-p53-p21 pathways. Int. Urol. Nephrol., 2019, 51(6), 1071-1078.
[] [PMID: 31089945]
Wakino, S.; Hasegawa, K.; Itoh, H. Sirtuin and metabolic kidney disease. Kidney Int., 2015, 88(4), 691-698.
[] [PMID: 26083654]
Ugur, S.; Ulu, R.; Dogukan, A.; Gurel, A.; Yigit, I.P.; Gozel, N.; Aygen, B.; Ilhan, N. The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity. Ren. Fail., 2015, 37(2), 332-336.
[] [PMID: 25594614]
Zhuo, L.; Fu, B.; Bai, X.; Zhang, B.; Wu, L.; Cui, J.; Cui, S.; Wei, R.; Chen, X.; Cai, G. NAD blocks high glucose induced mesangial hypertrophy via activation of the sirtuins-AMPK-mTOR pathway. Cell. Physiol. Biochem., 2011, 27(6), 681-690.
[] [PMID: 21691086]
Hussein, M.M.; Mahfouz, M.K. Effect of resveratrol and rosuvastatin on experimental diabetic nephropathy in rats. Biomed. Pharmacother., 2016, 82, 685-692.
[] [PMID: 27470412]

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