To Explore the Putative Molecular Targets of Diabetic Nephropathy
and their Inhibition Utilizing Potential Phytocompounds

Banani      Bhattacharjee; Arnob      Chakrovorty; Maharaj      Biswas; Asmita      Samadder; Sisir      Nandi
doi:10.2174/0929867330666230519112312
Abstract

Background: This review critically addresses the putative molecular targets of Diabetic Nephropathy (DN) and screens effective phytocompounds that can be therapeutically beneficial, and highlights their mechanistic modalities of action.
Introduction: DN has become one of the most prevalent complications of clinical hyperglycemia, with individual-specific variations in the disease spectrum that leads to fatal consequences. Diverse etiologies involving oxidative and nitrosative stress, activation of polyol pathway, inflammasome formation, Extracellular Matrix (ECM) modifications, fibrosis, and change in dynamics of podocyte functional and mesangial cell proliferation adds up to the clinical complexity of DN. Current synthetic therapeutics lacks target-specific approach, and is associated with the development of inevitable residual toxicity and drug resistance. Phytocompounds provides a vast diversity of novel compounds that can become an alternative therapeutic approach to combat the DN.
Methods: Relevant publications were searched and screened from research databases like GOOGLE SCHOLAR, PUBMED and SCISEARCH. Out of 4895 publications, the most relevant publications were selected and included in this article.
Result: This study critically reviews over 60 most promising phytochemical and provides with their molecular targets, that can be of pharmacological significance in context to current treatment and concomitant research in DN.
Conclusion: This review highlights those most promising phytocompounds that have the potential of becoming new safer naturally-sourced therapeutic candidates and demands further attention at clinical level.
Keywords: Diabetic nephropathy, type 2 diabetes, kidney, phytocompound, molecular targets, renal disease.
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[1]
Diabetes in America.  National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases., 1995. Available from: https://diabetes.org/healthylivingnews?gad=1

[2]
Genuth, S.; Alberti, K.G.; Bennett, P.; Buse, J.; Defronzo, R.; Kahn, R.; Kitzmiller, J.; Knowler, W.C.; Lebovitz, H.; Lernmark, A.; Nathan, D.; Palmer, J.; Rizza, R.; Saudek, C.; Shaw, J.; Steffes, M.; Stern, M.; Tuomilehto, J.; Zimmet, P. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care,  2003, 26(11), 3160-3167.
 [http://dx.doi.org/10.2337/diacare.26.11.3160] [PMID:  14578255]

[3]
Daneman, D. Type 1 diabetes. Lancet,  2006, 367(9513), 847-858.
 [http://dx.doi.org/10.1016/S0140-6736(06)68341-4] [PMID:  16530579]

[4]
Chatterjee, S.; Khunti, K.; Davies, M.J. Type 2 diabetes. Lancet,  2017, 389(10085), 2239-2251.
 [http://dx.doi.org/10.1016/S0140-6736(17)30058-2] [PMID:  28190580]

[5]
Samadder, A.; Das, J.; Das, S.; De, A.; Saha, S.K.; Bhattacharyya, S.S.; Khuda-Bukhsh, A.R. Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings. Toxicol. Appl. Pharmacol.,  2013, 267(1), 57-73.
 [http://dx.doi.org/10.1016/j.taap.2012.12.018] [PMID:  23276653]

[6]
Samadder, A.; Das, S.; Das, J.; Khuda-Bukhsh, A.R. Relative efficacies of insulin and poly (lactic-co-glycolic) acid encapsulated nano-insulin in modulating certain significant biomarkers in arsenic intoxicated L6 cells. Colloids Surf. B Biointerfaces,  2013, 109, 10-19.
 [http://dx.doi.org/10.1016/j.colsurfb.2013.03.028] [PMID:  23603037]

[7]
Rayanagoudar, G.; Hashi, A.A.; Zamora, J.; Khan, K.S.; Hitman, G.A.; Thangaratinam, S. Quantification of the type 2 diabetes risk in women with gestational diabetes: A systematic review and meta-analysis of 95,750 women. Diabetologia,  2016, 59(7), 1403-1411.
 [http://dx.doi.org/10.1007/s00125-016-3927-2] [PMID:  27073002]

[8]
Su, W.; Cao, R.; He, Y.C.; Guan, Y.F.; Ruan, X.Z. Crosstalk of hyperglycemia and dyslipidemia in diabetic kidney disease. Kidney Dis.,  2017, 3(4), 171-180.
 [http://dx.doi.org/10.1159/000479874] [PMID:  29344511]

[9]
Laakso, M. Hyperglycemia and cardiovascular disease in type 2 diabetes. Diabetes,  1999, 48(5), 937-942.
 [http://dx.doi.org/10.2337/diabetes.48.5.937] [PMID:  10331395]

[10]
Madhusudhanan, J.; Suresh, G.; Devanathan, V. Neurodegeneration in type 2 diabetes: Alzheimer’s as a case study. Brain Behav.,  2020, 10(5), e01577.
 [http://dx.doi.org/10.1002/brb3.1577] [PMID:  32170854]

[11]
Morais, T.; Seabra, A.L.; Patrício, B.G.; Guimarães, M.; Nora, M.; Oliveira, P.F.; Alves, M.G.; Monteiro, M.P. Visceral adipose tissue displays unique metabolomic fingerprints in obesity, pre-diabetes and type 2 diabetes. Int. J. Mol. Sci.,  2021, 22(11), 5695.
 [http://dx.doi.org/10.3390/ijms22115695] [PMID:  34071774]

[12]
Chouchani, E.T.; Kajimura, S. Metabolic adaptation and maladaptation in adipose tissue. Nat. Metab.,  2019, 1(2), 189-200.
 [http://dx.doi.org/10.1038/s42255-018-0021-8] [PMID:  31903450]

[13]
Olefsky, J.M. The insulin receptor: its role in insulin resistance of obesity and diabetes. Diabetes,  1976, 25(12), 1154-1161.
 [http://dx.doi.org/10.2337/diab.25.12.1154] [PMID:  791735]

[14]
Sobrevia, L.; Mann, G.E. Dysfunction of the endothelial nitric oxide signalling pathway in diabetes and hyperglycaemia. Exp. Physiol.,  1997, 82(3), 423-452.
 [http://dx.doi.org/10.1113/expphysiol.1997.sp004038] [PMID:  9179565]

[15]
Khalid, M.; Alkaabi, J.; Khan, M.A.B.; Adem, A. Insulin signal transduction perturbations in insulin resistance. Int. J. Mol. Sci.,  2021, 22(16), 8590.
 [http://dx.doi.org/10.3390/ijms22168590] [PMID:  34445300]

[16]
Svensson, M.; Eriksson, J.W. Insulin resistance in diabetic nephropathy - cause or consequence? Diabetes Metab. Res. Rev.,  2006, 22(5), 401-410.
 [http://dx.doi.org/10.1002/dmrr.648] [PMID:  16703644]

[17]
Boström, P.; Andersson, L.; Vind, B.; Håversen, L.; Rutberg, M.; Wickström, Y.; Larsson, E.; Jansson, P.A.; Svensson, M.K.; Brånemark, R.; Ling, C.; Beck-Nielsen, H.; Borén, J.; Højlund, K.; Olofsson, S.O. The SNARE protein SNAP23 and the SNARE-interacting protein Munc18c in human skeletal muscle are implicated in insulin resistance/type 2 diabetes. Diabetes,  2010, 59(8), 1870-1878.
 [http://dx.doi.org/10.2337/db09-1503] [PMID:  20460426]

[18]
Rezaei Farimani, A.; Saidijam, M.; Goodarzi, M.T.; Yadegar Azari, R.; Asadi, S.; Zarei, S.; Shabab, N. Effect of resveratrol supplementation on the SNARE proteins expression in adipose tissue of stroptozotocin-nicotinamide induced type 2 diabetic rats. Iran. J. Med. Sci.,  2015, 40(3), 248-255.
 [PMID:  25999625]

[19]
Samadder, A.; Chakraborty, D.; De, A.; Bhattacharyya, S.S.; Bhadra, K.; Khuda-Bukhsh, A.R. Possible signaling cascades involved in attenuation of alloxan-induced oxidative stress and hyperglycemia in mice by ethanolic extract of Syzygium jambolanum: Drug-DNA interaction with calf thymus DNA as target. Eur. J. Pharm. Sci.,  2011, 44(3), 207-217.
 [http://dx.doi.org/10.1016/j.ejps.2011.07.012] [PMID:  21839831]

[20]
Esper, A.M.; Moss, M.; Martin, G.S. The effect of diabetes mellitus on organ dysfunction with sepsis: an epidemiological study. Crit. Care,  2009, 13(1), R18.
 [http://dx.doi.org/10.1186/cc7717] [PMID:  19216780]

[21]
Oschatz, E.; Müllner, M.; Herkner, H.; Laggner, A.N. Multiple organ failure and prognosis in adult patients with diabetic ketoacidosis. Wien. Klin. Wochenschr.,  1999, 111(15), 590-595.
 [PMID:  10483673]

[22]
Keane, W.F.; Zhang, Z.; Lyle, P.A.; Cooper, M.E.; de Zeeuw, D.; Grunfeld, J.P.; Lash, J.P.; McGill, J.B.; Mitch, W.E.; Remuzzi, G.; Shahinfar, S.; Snapinn, S.M.; Toto, R.; Brenner, B.M. Risk scores for predicting outcomes in patients with type 2 diabetes and nephropathy: The RENAAL study. Clin. J. Am. Soc. Nephrol.,  2006, 1(4), 761-767.
 [http://dx.doi.org/10.2215/CJN.01381005] [PMID:  17699284]

[23]
Gross, J.L.; de Azevedo, M.J.; Silveiro, S.P.; Canani, L.H.; Caramori, M.L.; Zelmanovitz, T. Diabetic nephropathy: Diagnosis, prevention, and treatment. Diabetes Care,  2005, 28(1), 164-176.
 [http://dx.doi.org/10.2337/diacare.28.1.164] [PMID:  15616252]

[24]
Umanath, K.; Lewis, J.B. Update on diabetic nephropathy: Core curriculum 2018. Am. J. Kidney Dis.,  2018, 71(6), 884-895.
 [http://dx.doi.org/10.1053/j.ajkd.2017.10.026] [PMID:  29398179]

[25]
Samsu, N. Diabetic nephropathy: Challenges in pathogenesis, diagnosis, and treatment. BioMed Res. Int.,  2021, 2021, 1-17.
 [http://dx.doi.org/10.1155/2021/1497449] [PMID:  34307650]

[26]
Strippoli, G.F.M.; Bonifati, C.; Craig, M.E.; Navaneethan, S.D.; Craig, J.C. Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease. Cochrane Libr.,  2006, 2006(4), CD006257.
 [http://dx.doi.org/10.1002/14651858.CD006257] [PMID:  17054288]

[27]
Anderson, S.; Rennke, H.G.; Brenner, B.M. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J. Clin. Invest.,  1986, 77(6), 1993-2000.
 [http://dx.doi.org/10.1172/JCI112528] [PMID:  3011863]

[28]
Mittler, R. ROS are good. Trends Plant Sci.,  2017, 22(1), 11-19.
 [http://dx.doi.org/10.1016/j.tplants.2016.08.002] [PMID:  27666517]

[29]
David, L.; Nelson, D.L.; Cox, M.M.; Stiedemann, L.; McGlynn, M.E., Jr; Fay, M.R. Lehninger principles of biochemistry; Macmillan, 2008. 

[30]
Zhang, J.; Wang, X.; Vikash, V.; Ye, Q.; Wu, D.; Liu, Y.; Dong, W. ROS and ROS-mediated cellular signaling. Oxid. Med. Cell. Longev.,  2016, 2016, 1-18.
 [http://dx.doi.org/10.1155/2016/4350965]

[31]
Martínez, M.C.; Andriantsitohaina, R. Reactive nitrogen species: Molecular mechanisms and potential significance in health and disease. Antioxid. Redox Signal.,  2009, 11(3), 669-702.
 [http://dx.doi.org/10.1089/ars.2007.1993] [PMID:  19014277]

[32]
Dupré-Crochet, S.; Erard, M. Nüβe, O. ROS production in phagocytes: Why, when, and where? J. Leukoc. Biol.,  2013, 94(4), 657-670.
 [http://dx.doi.org/10.1189/jlb.1012544] [PMID:  23610146]

[33]
Brieger, K.; Schiavone, S.; Miller, J., Jr; Krause, K.H. Reactive oxygen species: From health to disease. Swiss Med. Wkly.,  2012, 142, w13659.
 [http://dx.doi.org/10.4414/smw.2012.13659] [PMID:  22903797]

[34]
Møller, P.; Wallin, H. Adduct formation, mutagenesis and nucleotide excision repair of DNA damage produced by reactive oxygen species and lipid peroxidation product. Mutat. Res. Rev. Mutat. Res.,  1998, 410(3), 271-290.
 [http://dx.doi.org/10.1016/S1383-5742(97)00041-0] [PMID:  9630671]

[35]
Yajima, D.; Motani, H.; Hayakawa, M.; Sato, Y.; Sato, K.; Iwase, H. The relationship between cell membrane damage and lipid peroxidation under the condition of hypoxia-reoxygenation: Analysis of the mechanism using antioxidants and electron transport inhibitors. Cell Biochem.,  2009, 27(6), 338-343.
 [http://dx.doi.org/10.1002/cbf.1578]

[36]
Lin, T.K.; Cheng, C.H.; Chen, S.D.; Liou, C.W.; Huang, C.R.; Chuang, Y.C. Mitochondrial dysfunction and oxidative stress promote apoptotic cell death in the striatum via cytochrome c/caspase-3 signaling cascade following chronic rotenone intoxication in rats. Int. J. Mol. Sci.,  2012, 13(7), 8722-8739.
 [http://dx.doi.org/10.3390/ijms13078722] [PMID:  22942730]

[37]
Kobayashi, N.; DeLano, F.A.; Schmid-Schönbein, G.W. Oxidative stress promotes endothelial cell apoptosis and loss of microvessels in the spontaneously hypertensive rats. Arterioscler. Thromb. Vasc. Biol.,  2005, 25(10), 2114-2121.
 [http://dx.doi.org/10.1161/01.ATV.0000178993.13222.f2] [PMID:  16037565]

[38]
Kashihara, N.; Haruna, Y.; Kondeti, V.K.; Kanwar, Y.S. Oxidative stress in diabetic nephropathy. Curr. Med. Chem.,  2010, 17(34), 4256-4269.
 [http://dx.doi.org/10.2174/092986710793348581] [PMID:  20939814]

[39]
Tan, A.L.Y.; Forbes, J.M.; Cooper, M.E. AGE, RAGE, and ROS in diabetic nephropathy. Semin. Nephrol.,  2007, 27(2), 130-143.
 [http://dx.doi.org/10.1016/j.semnephrol.2007.01.006] [PMID:  17418682]

[40]
Bohlender, J.M.; Franke, S.; Stein, G.; Wolf, G. Advanced glycation end products and the kidney. Am. J. Physiol. Renal Physiol.,  2005, 289(4), F645-F659.
 [http://dx.doi.org/10.1152/ajprenal.00398.2004] [PMID:  16159899]

[41]
Ho, F.M.; Liu, S.H.; Liau, C.S.; Huang, P.J.; Lin-Shiau, S.Y. High glucose-induced apoptosis in human endothelial cells is mediated by sequential activations of c-Jun NH(2)-terminal kinase and caspase-3. Circulation,  2000, 101(22), 2618-2624.
 [http://dx.doi.org/10.1161/01.CIR.101.22.2618] [PMID:  10840014]

[42]
Konishi, H.; Tanaka, M.; Takemura, Y.; Matsuzaki, H.; Ono, Y.; Kikkawa, U.; Nishizuka, Y. Activation of protein kinase C by tyrosine phosphorylation in response to H2O2. Proc. Natl. Acad. Sci.,  1997, 94(21), 11233-11237.
 [http://dx.doi.org/10.1073/pnas.94.21.11233] [PMID:  9326592]

[43]
Burg, M.B. Coordinate regulation of organic osmolytes in renal cells. Kidney Int.,  1996, 49(6), 1684-1685.
 [http://dx.doi.org/10.1038/ki.1996.247] [PMID:  8743477]

[44]
Burger-Kentischer, A.; Müller, E.; März, J.; Fraek, M.L.; Thurau, K.; Beck, F.X. Hypertonicity-induced accumulation of organic osmolytes in papillary interstitial cells. Kidney Int.,  1999, 55(4), 1417-1425.
 [http://dx.doi.org/10.1046/j.1523-1755.1999.00382.x] [PMID:  10201006]

[45]
Chung, S.S.M.; Ho, E.C.M.; Lam, K.S.L.; Chung, S.K. Contribution of polyol pathway to diabetes-induced oxidative stress. J. Am. Soc. Nephrol.,  2003, 14(8)(Suppl. 3), S233-S236.
 [http://dx.doi.org/10.1097/01.ASN.0000077408.15865.06] [PMID:  12874437]

[46]
Shah, V.O.; Dorin, R.I.; Sun, Y.; Braun, M.; Zager, P.G. Aldose reductase gene expression is increased in diabetic nephropathy. J. Clin. Endocrinol. Metab.,  1997, 82(7), 2294-2298.
 [http://dx.doi.org/10.1210/jc.82.7.2294] [PMID:  9215310]

[47]
Williamson, J.R.; Chang, K.; Frangos, M.; Hasan, K.S.; Ido, Y.; Kawamura, T.; Nyengaard, J.R.; Den Enden, M.; Kilo, C.; Tilton, R.G. Hyperglycemic pseudohypoxia and diabetic complications. Diabetes,  1993, 42(6), 801-813.
 [http://dx.doi.org/10.2337/diab.42.6.801] [PMID:  8495803]

[48]
Cheng, X.; Ni, B.; Zhang, Z.; Liu, Q.; Wang, L.; Ding, Y.; Hu, Y. Polyol pathway mediates enhanced degradation of extracellular matrix via p38 MAPK activation in intervertebral disc of diabetic rats. Connect. Tissue Res.,  2013, 54(2), 118-122.
 [http://dx.doi.org/10.3109/03008207.2012.754886] [PMID:  23215968]

[49]
Dunlop, M. Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney Int.,  2000, 58, S3-S12.
 [http://dx.doi.org/10.1046/j.1523-1755.2000.07702.x] [PMID:  10997684]

[50]
Niimi, N.; Yako, H.; Takaku, S.; Chung, S.K.; Sango, K. Aldose reductase and the polyol pathway in schwann cells: Old and new problems. Int. J. Mol. Sci.,  2021, 22(3), 1031.
 [http://dx.doi.org/10.3390/ijms22031031] [PMID:  33494154]

[51]
Zill, H.; Bek, S.; Hofmann, T.; Huber, J.; Frank, O.; Lindenmeier, M.; Weigle, B.; Erbersdobler, H.F.; Scheidler, S.; Busch, A.E.; Faist, V. RAGE-mediated MAPK activation by food-derived AGE and non-AGE products. Biochem. Biophys. Res. Commun.,  2003, 300(2), 311-315.
 [http://dx.doi.org/10.1016/S0006-291X(02)02856-5] [PMID:  12504085]

[52]
Hu, H.; Jiang, H.; Ren, H.; Hu, X.; Wang, X.; Han, C. AGEs and chronic subclinical inflammation in diabetes: Disorders of immune system. Diabetes Metab. Res. Rev.,  2015, 31(2), 127-137.
 [http://dx.doi.org/10.1002/dmrr.2560] [PMID:  24846076]

[53]
Qiu, Y.; Tang, L. Roles of the NLRP3 inflammasome in the pathogenesis of diabetic nephropathy. Pharmacol. Res.,  2016, 114, 251-264.
 [http://dx.doi.org/10.1016/j.phrs.2016.11.004] [PMID:  27826011]

[54]
Wang, J.; Shen, X.; Liu, J.; Chen, W.; Wu, F.; Wu, W.; Meng, Z.; Zhu, M.; Miao, C. High glucose mediates NLRP3 inflammasome activation via upregulation of ELF3 expression. Cell Death Dis.,  2020, 11(5), 383.
 [http://dx.doi.org/10.1038/s41419-020-2598-6] [PMID:  32439949]

[55]
de Zoete, M.R.; Palm, N.W.; Zhu, S.; Flavell, R.A. Inflammasomes. Cold Spring Harb. Perspect. Biol.,  2014, 6(12), a016287.
 [http://dx.doi.org/10.1101/cshperspect.a016287] [PMID:  25324215]

[56]
Müller, R.; Daniel, C.; Hugo, C.; Amann, K.; Mielenz, D.; Endlich, K.; Braun, T.; van der Veen, B.; Heeringa, P.; Schett, G.; Zwerina, J. The mitogen-activated protein kinase p38&#945; regulates tubular damage in murine anti-glomerular basement membrane nephritis. PLoS One,  2013, 8(2), e56316.
 [http://dx.doi.org/10.1371/journal.pone.0056316] [PMID:  23441175]

[57]
Navarro-González, J.F.; Mora-Fernández, C. The role of inflammatory cytokines in diabetic nephropathy. J. Am. Soc. Nephrol.,  2008, 19(3), 433-442.
 [http://dx.doi.org/10.1681/ASN.2007091048] [PMID:  18256353]

[58]
Okada, M.; Matsuzawa, A.; Yoshimura, A.; Ichijo, H. The lysosome rupture-activated TAK1-JNK pathway regulates NLRP3 inflammasome activation. J. Biol. Chem.,  2014, 289(47), 32926-32936.
 [http://dx.doi.org/10.1074/jbc.M114.579961] [PMID:  25288801]

[59]
Yang, R.; Trevillyan, J.M. c-Jun N-terminal kinase pathways in diabetes. Int. J. Biochem. Cell Biol.,  2008, 40(12), 2702-2706.
 [http://dx.doi.org/10.1016/j.biocel.2008.06.012] [PMID:  18678273]

[60]
Harijith, A.; Ebenezer, D.L.; Natarajan, V. Reactive oxygen species at the crossroads of inflammasome and inflammation. Front. Physiol.,  2014, 5, 352.
 [http://dx.doi.org/10.3389/fphys.2014.00352] [PMID:  25324778]

[61]
Sun, X.; Jiao, X.; Ma, Y.; Liu, Y.; Zhang, L.; He, Y.; Chen, Y. Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome. Biochem. Biophys. Res. Commun.,  2016, 481(1-2), 63-70.
 [http://dx.doi.org/10.1016/j.bbrc.2016.11.017] [PMID:  27833015]

[62]
Kolset, S.O.; Reinholt, F.P.; Jenssen, T. Diabetic nephropathy and extracellular matrix. J. Histochem. Cytochem.,  2012, 60(12), 976-986.
 [http://dx.doi.org/10.1369/0022155412465073] [PMID:  23103723]

[63]
Moriya, T.; Groppoli, T.J.; Kim, Y.; Mauer, M. Quantitative immunoelectron microscopy of type VI collagen in glomeruli in type I diabetic patients. Kidney Int.,  2001, 59(1), 317-323.
 [http://dx.doi.org/10.1046/j.1523-1755.2001.00493.x] [PMID:  11135085]

[64]
Yard, B.A.; Kahlert, S.; Engelleiter, R.; Resch, S.; Waldherr, R.; Groffen, A.J.; van den Heuvel, L.P.W.J.; van der Born, J.; Berden, J.H.M.; Kröger, S.; Hafner, M.; van der Woude, F.J. Decreased glomerular expression of agrin in diabetic nephropathy and podocytes, cultured in high glucose medium. Nephron, Exp. Nephrol.,  2001, 9(3), 214-222.
 [http://dx.doi.org/10.1159/000052614] [PMID:  11340306]

[65]
Holmquist, P.; Torffvit, O. Urinary transforming growth factor-β 1, collagen IV and the effect of insulin in children at diagnosis of diabetes mellitus. Scand. J. Urol. Nephrol.,  2009, 43(2), 142-147.
 [http://dx.doi.org/10.1080/00365590802502111] [PMID:  18979373]

[66]
Stokes, M.B.; Holler, S.; Cui, Y.; Hudkins, K.L.; Eitner, F.; Fogo, A.; Alpers, C.E. Expression of decorin, biglycan, and collagen type I in human renal fibrosing disease. Kidney Int.,  2000, 57(2), 487-498.
 [http://dx.doi.org/10.1046/j.1523-1755.2000.00868.x] [PMID:  10652025]

[67]
Figarola, J.L.; Scott, S.; Loera, S.; Xi, B.; Synold, T.; Rahbar, S. Renoprotective and lipid-lowering effects of LR compounds, novel advanced glycation end product inhibitors, in streptozotocin-induced diabetic rats. Ann. N. Y. Acad. Sci.,  2005, 1043(1), 767-776.
 [http://dx.doi.org/10.1196/annals.1333.089] [PMID:  16037304]

[68]
Dimas, G.G.; Didangelos, T.P.; Grekas, D.M. Matrix gelatinases in atherosclerosis and diabetic nephropathy: progress and challenges. Curr. Vasc. Pharmacol.,  2017, 15(6), 557-565.
 [PMID:  28155628]

[69]
Srivastava, S.P.; Koya, D.; Kanasaki, K. MicroRNAs in kidney fibrosis and diabetic nephropathy: Roles on EMT and EndMT. BioMed Res. Int.,  2013, 2013, 1-10.
 [http://dx.doi.org/10.1155/2013/125469] [PMID:  24089659]

[70]
Zeisberg, M.; Bottiglio, C.; Kumar, N.; Maeshima, Y.; Strutz, F.; Müller, G.A.; Kalluri, R. Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models. Am. J. Physiol. Renal Physiol.,  2003, 285(6), F1060-F1067.
 [http://dx.doi.org/10.1152/ajprenal.00191.2002] [PMID:  12915382]

[71]
Kalluri, R.; Weinberg, R.A. The basics of epithelial-mesenchymal transition. J. Clin. Invest.,  2009, 119(6), 1420-1428.
 [http://dx.doi.org/10.1172/JCI39104] [PMID:  19487818]

[72]
Tan, T.K.; Zheng, G.; Hsu, T.T.; Wang, Y.; Lee, V.W.S.; Tian, X.; Wang, Y.; Cao, Q.; Wang, Y.; Harris, D.C.H. Macrophage matrix metalloproteinase-9 mediates epithelial-mesenchymal transition in vitro in murine renal tubular cells. Am. J. Pathol.,  2010, 176(3), 1256-1270.
 [http://dx.doi.org/10.2353/ajpath.2010.090188] [PMID:  20075196]

[73]
Jiang, Q.; Wang, Y.; Hao, Y.; Juan, L.; Teng, M.; Zhang, X.; Li, M.; Wang, G.; Liu, Y. miR2Disease: A manually curated database for microRNA deregulation in human disease. Nucleic Acids Res.,  2009, 37(S1), D98-D104.
 [http://dx.doi.org/10.1093/nar/gkn714] [PMID:  18927107]

[74]
Bracken, C.P.; Gregory, P.A.; Kolesnikoff, N.; Bert, A.G.; Wang, J.; Shannon, M.F.; Goodall, G.J. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res.,  2008, 68(19), 7846-7854.
 [http://dx.doi.org/10.1158/0008-5472.CAN-08-1942] [PMID:  18829540]

[75]
Pavenstädt, H.; Kriz, W.; Kretzler, M. Cell biology of the glomerular podocyte. Physiol. Rev.,  2003, 83(1), 253-307.
 [http://dx.doi.org/10.1152/physrev.00020.2002] [PMID:  12506131]

[76]
Abboud, H.E. Mesangial cell biology. Exp. Cell Res.,  2012, 318(9), 979-985.
 [http://dx.doi.org/10.1016/j.yexcr.2012.02.025] [PMID:  22414873]

[77]
Schöcklmann, H.O.; Lang, S.; Sterzel, R.B. Regulation of mesangial cell proliferation. Kidney Int.,  1999, 56(4), 1199-1207.
 [http://dx.doi.org/10.1046/j.1523-1755.1999.00710.x] [PMID:  10610410]

[78]
Simonson, M.S. Phenotypic transitions and fibrosis in diabetic nephropathy. Kidney Int.,  2007, 71(9), 846-854.
 [http://dx.doi.org/10.1038/sj.ki.5002180] [PMID:  17342177]

[79]
Li, J.J.; Kwak, S.J.; Jung, D.S.; Kim, J.J.; Yoo, T.H.; Ryu, D.R.; Han, S.H.; Choi, H.Y.; Lee, J.E.; Moon, S.J.; Kim, D.K.; Han, D.S.; Kang, S.W. Podocyte biology in diabetic nephropathy. Kidney Int.,  2007, 72(106), S36-S42.
 [http://dx.doi.org/10.1038/sj.ki.5002384] [PMID:  17653209]

[80]
Bai, Y.; Wang, L.; Li, Y.; Liu, S.; Li, J.; Wang, H.; Huang, H. High ambient glucose levels modulates the production of MMP-9 and alpha5(IV) collagen by cultured podocytes. Cell. Physiol. Biochem.,  2006, 17(1-2), 57-68.
 [http://dx.doi.org/10.1159/000091464] [PMID:  16543722]

[81]
Xu, Z.G.; Yoo, T.H.; Ryu, D.R.; Park, H.C.; Ha, S.K.; Han, D.S.; Adler, S.G.; Natarajan, R.; Kang, S.W. Angiotensin II receptor blocker inhibits p27Kip1 expression in glucose-stimulated podocytes and in diabetic glomeruli. Kidney Int.,  2005, 67(3), 944-952.
 [http://dx.doi.org/10.1111/j.1523-1755.2005.00158.x] [PMID:  15698433]

[82]
Lee, E.Y.; Shim, M.S.; Kim, M.J.; Hong, S.Y.; Shin, Y.G.; Chung, C.H. Angiotensin II receptor blocker attenuates overexpression of vascular endothelial growth factor in diabetic podocytes. Exp. Mol. Med.,  2004, 36(1), 65-70.
 [http://dx.doi.org/10.1038/emm.2004.9] [PMID:  15031673]

[83]
Tufro, A.; Veron, D. VEGF and podocytes in diabetic nephropathy. Semin. Nephrol.,  2012, 32(4), 385-393.
 [http://dx.doi.org/10.1016/j.semnephrol.2012.06.010] [PMID:  22958493]

[84]
Veron, D.; Reidy, K.; Bertuccio, C.; Techman, J.; Villegas, G.; Jimenez, J.; Shen, W.; Kopp, J.; Thomas, D.; Tufro, A. Induction of podocyte VEGF-A overexpression in adult mice causes glomerular disease. Kidney Int.,  2010, 77, 989-999.
 [http://dx.doi.org/10.1038/ki.2010.64] [PMID:  20375978]

[85]
Nijenhuis, T.; Sloan, A.J.; Hoenderop, J.G.J.; Flesche, J.; van Goor, H.; Kistler, A.D.; Bakker, M.; Bindels, R.J.M.; de Boer, R.A.; Möller, C.C.; Hamming, I.; Navis, G.; Wetzels, J.F.M.; Berden, J.H.M.; Reiser, J.; Faul, C.; van der Vlag, J. Angiotensin II contributes to podocyte injury by increasing TRPC6 expression via an NFAT-mediated positive feedback signaling pathway. Am. J. Pathol.,  2011, 179(4), 1719-1732.
 [http://dx.doi.org/10.1016/j.ajpath.2011.06.033] [PMID:  21839714]

[86]
Lin, C.L.; Wang, J.Y.; Huang, Y.T.; Kuo, Y.H.; Surendran, K.; Wang, F.S. Wnt/beta-catenin signaling modulates survival of high glucose-stressed mesangial cells. J. Am. Soc. Nephrol.,  2006, 17(10), 2812-2820.
 [http://dx.doi.org/10.1681/ASN.2005121355] [PMID:  16943306]

[87]
Lin, C.L.; Wang, J.Y.; Ko, J.Y.; Huang, Y.T.; Kuo, Y.H.; Wang, F.S. Dickkopf-1 promotes hyperglycemia-induced accumulation of mesangial matrix and renal dysfunction. J. Am. Soc. Nephrol.,  2010, 21(1), 124-135.
 [http://dx.doi.org/10.1681/ASN.2008101059] [PMID:  20019166]

[88]
Tung, C.W.; Hsu, Y.C.; Shih, Y.H.; Chang, P.J.; Lin, C.L. Glomerular mesangial cell and podocyte injuries in diabetic nephropathy. Nephrology (Carlton),  2018, 23(S4), 32-37.
 [http://dx.doi.org/10.1111/nep.13451] [PMID:  30298646]

[89]
Lin, C.L.; Wang, J.Y.; Ko, J.Y.; Surendran, K.; Huang, Y.T.; Kuo, Y.H.; Wang, F.S. Superoxide destabilization of beta-catenin augments apoptosis of high-glucose-stressed mesangial cells. Endocrinology,  2008, 149(6), 2934-2942.
 [http://dx.doi.org/10.1210/en.2007-1372] [PMID:  18339714]

[90]
Wang, F.; Fisher, S.A.; Zhong, J.; Wu, Y.; Yang, P. Superoxide dismutase 1 in vivo ameliorates maternal diabetes mellitus-induced apoptosis and heart defects through restoration of impaired Wnt signaling. Circ. Cardiovasc. Genet.,  2015, 8(5), 665-676.
 [http://dx.doi.org/10.1161/CIRCGENETICS.115.001138] [PMID:  26232087]

[91]
Lin, C.L.; Lee, P.H.; Hsu, Y.C.; Lei, C.C.; Ko, J.Y.; Chuang, P.C.; Huang, Y.T.; Wang, S.Y.; Wu, S.L.; Chen, Y.S.; Chiang, W.C.; Reiser, J.; Wang, F.S. MicroRNA-29a promotion of nephrin acetylation ameliorates hyperglycemia-induced podocyte dysfunction. J. Am. Soc. Nephrol.,  2014, 25(8), 1698-1709.
 [http://dx.doi.org/10.1681/ASN.2013050527] [PMID:  24578127]

[92]
Li, X.; Chuang, P.Y.; D’Agati, V.D.; Dai, Y.; Yacoub, R.; Fu, J.; Xu, J.; Taku, O.; Premsrirut, P.K.; Holzman, L.B.; He, J.C. Nephrin preserves podocyte viability and glomerular structure and function in adult kidneys. J. Am. Soc. Nephrol.,  2015, 26(10), 2361-2377.
 [http://dx.doi.org/10.1681/ASN.2014040405] [PMID:  25644109]

[93]
Niranjan, T.; Bielesz, B.; Gruenwald, A.; Ponda, M.P.; Kopp, J.B.; Thomas, D.B.; Susztak, K. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat. Med.,  2008, 14(3), 290-298.
 [http://dx.doi.org/10.1038/nm1731] [PMID:  18311147]

[94]
Gruden, G.; Perin, P.; Camussi, G. Insight on the pathogenesis of diabetic nephropathy from the study of podocyte and mesangial cell biology. Curr. Diabetes Rev.,  2005, 1(1), 27-40.
 [http://dx.doi.org/10.2174/1573399052952622] [PMID:  18220580]

[95]
Kitsiou, P.V.; Tzinia, A.K.; Stetler-Stevenson, W.G.; Michael, A.F.; Fan, W.W.; Zhou, B.; Tsilibary, E.C. Glucose-induced changes in integrins and matrix-related functions in cultured human glomerular epithelial cells. Am. J. Physiol. Renal Physiol.,  2003, 284(4), F671-F679.
 [http://dx.doi.org/10.1152/ajprenal.00266.2002] [PMID:  12620921]

[96]
Endlich, N.; Sunohara, M.; Nietfeld, W.; Wolski, E.W.; Schiwek, D. KräNzlin, B.; Gretz, N.; Kriz, W.; Eickhoff, H.; Endlich, K. Analysis of differential gene expression in stretched podocytes: osteopontin enhances adaptation of podocytes to mechanical stress. FASEB J.,  2002, 16(13), 1-24.
 [http://dx.doi.org/10.1096/fj.02-0125fje] [PMID:  12354696]

[97]
Endlich, N.; Kress, K.R.; Reiser, J.; Uttenweiler, D.; Kriz, W.; Mundel, P.; Endlich, K. Podocytes respond to mechanical stress in vitro. J. Am. Soc. Nephrol.,  2001, 12(3), 413-422.
 [http://dx.doi.org/10.1681/ASN.V123413] [PMID:  11181788]

[98]
Safavi, M.; Foroumadi, A.; Abdollahi, M. The importance of synthetic drugs for type 2 diabetes drug discovery. Expert Opin. Drug Discov.,  2013, 8(11), 1339-1363.
 [http://dx.doi.org/10.1517/17460441.2013.837883] [PMID:  24050217]

[99]
Eggleton, J.S.; Jialal, I. Thiazolidinediones. In: StatPearls; StatPearls Publishing: Treasure Island, FL, 2021. 

[100]
Yki-Järvinen, H. Thiazolidinediones. N. Engl. J. Med.,  2004, 351(11), 1106-1118.
 [http://dx.doi.org/10.1056/NEJMra041001] [PMID:  15356308]

[101]
Rena, G.; Hardie, D.G.; Pearson, E.R. The mechanisms of action of metformin. Diabetologia,  2017, 60(9), 1577-1585.
 [http://dx.doi.org/10.1007/s00125-017-4342-z] [PMID:  28776086]

[102]
Hawley, S.A.; Ross, F.A.; Chevtzoff, C.; Green, K.A.; Evans, A.; Fogarty, S.; Towler, M.C.; Brown, L.J.; Ogunbayo, O.A.; Evans, A.M.; Hardie, D.G. Use of cells expressing γ subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab.,  2010, 11(6), 554-565.
 [http://dx.doi.org/10.1016/j.cmet.2010.04.001] [PMID:  20519126]

[103]
Vincent, M.F.; Marangos, P.J.; Gruber, H.E.; van den Berghe, G. Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes. Diabetes,  1991, 40(10), 1259-1266.
 [http://dx.doi.org/10.2337/diab.40.10.1259] [PMID:  1657665]

[104]
Rendell, M. The role of sulphonylureas in the management of type 2 diabetes mellitus. Drugs,  2004, 64(12), 1339-1358.
 [http://dx.doi.org/10.2165/00003495-200464120-00006] [PMID:  15200348]

[105]
Groop, L.C.; Pelkonen, R.; Koskimies, S.; Bottazzo, G.F.; Doniach, D. Secondary failure to treatment with oral antidiabetic agents in non-insulin-dependent diabetes. Diabetes Care,  1986, 9(2), 129-133.
 [http://dx.doi.org/10.2337/diacare.9.2.129] [PMID:  3516607]

[106]
Yildiz, B.; Gürlek, A. Failure of sulfonylureas in type 2 diabetes. Horm. Metab. Res.,  1999, 31(4), 293-294.
 [http://dx.doi.org/10.1055/s-2007-978737] [PMID:  10333089]

[107]
Guardado-Mendoza, R.; Prioletta, A.; Jiménez-Ceja, L.M.; Sosale, A.; Folli, F. State of the art paper The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus. Arch. Med. Sci.,  2013, 5(5), 936-943.
 [http://dx.doi.org/10.5114/aoms.2013.34991] [PMID:  24273582]

[108]
Hansen, A.M.K.; Christensen, I.T.; Hansen, J.B.; Carr, R.D.; Ashcroft, F.M.; Wahl, P. Differential interactions of nateglinide and repaglinide on the human β-cell sulphonylurea receptor 1. Diabetes,  2002, 51(9), 2789-2795.
 [http://dx.doi.org/10.2337/diabetes.51.9.2789] [PMID:  12196472]

[109]
Halas, C.J. Nateglinide. Am. J. Health Syst. Pharm.,  2001, 58(13), 1200-1205.
 [http://dx.doi.org/10.1093/ajhp/58.13.1200] [PMID:  11449877]

[110]
Klag, M.J.; Whelton, P.K.; Randall, B.L.; Neaton, J.D.; Brancati, F.L.; Ford, C.E.; Shulman, N.B.; Stamler, J. Blood pressure and end-stage renal disease in men. N. Engl. J. Med.,  1996, 334(1), 13-18.
 [http://dx.doi.org/10.1056/NEJM199601043340103] [PMID:  7494564]

[111]
Lee, G.S. Retarding the progression of diabetic nephropathy in type 2 diabetes mellitus: Focus on hypertension and proteinuria. Ann. Acad. Med. Singap.,  2005, 34(1), 24-30.
 [PMID:  15726216]

[112]
Yacoub, R.; Campbell, K.N. Inhibition of RAS in diabetic nephropathy. Int. J. Nephrol. Renovasc. Dis.,  2015, 8, 29-40.
 [PMID:  25926752]

[113]
Kshirsagar, A.V.; Joy, M.S.; Hogan, S.L.; Falk, R.J.; Colindres, R.E. Effect of ACE inhibitors in diabetic and nondiabetic chronic renal disease: A systematic overview of randomized placebo-controlled trials. Am. J. Kidney Dis.,  2000, 35(4), 695-707.
 [http://dx.doi.org/10.1016/S0272-6386(00)70018-7] [PMID:  10739792]

[114]
Noel Van Buren, P.; Toto, R. Current update in the management of diabetic nephropathy. Curr. Diabetes Rev.,  2013, 9(1), 62-77.
 [http://dx.doi.org/10.2174/157339913804143207] [PMID:  23167665]

[115]
Sharma, K.; Ix, J.H.; Mathew, A.V.; Cho, M.; Pflueger, A.; Dunn, S.R.; Francos, B.; Sharma, S.; Falkner, B.; McGowan, T.A.; Donohue, M. RamachandraRao, S.; Xu, R.; Fervenza, F.C.; Kopp, J.B. Pirfenidone for diabetic nephropathy. J. Am. Soc. Nephrol.,  2011, 22(6), 1144-1151.
 [http://dx.doi.org/10.1681/ASN.2010101049] [PMID:  21511828]

[116]
Li, R.; Xing, J.; Mu, X.; Wang, H.; Zhang, L.; Zhao, Y.; Zhang, Y. Sulodexide therapy for the treatment of diabetic nephropathy, a meta-analysis and literature review. Drug Des. Devel. Ther.,  2015, 9, 6275-6283.
 [PMID:  26664049]

[117]
Soma, J.; Sugawara, T.; Huang, Y.D.; Nakajima, J.; Kawamura, M. Tranilast slows the progression of advanced diabetic nephropathy. Nephron J.,  2002, 92(3), 693-698.
 [http://dx.doi.org/10.1159/000064071] [PMID:  12372957]

[118]
Tuttle, K.R.; Bakris, G.L.; Toto, R.D.; McGill, J.B.; Hu, K.; Anderson, P.W. The effect of ruboxistaurin on nephropathy in type 2 diabetes. Diabetes Care,  2005, 28(11), 2686-2690.
 [http://dx.doi.org/10.2337/diacare.28.11.2686] [PMID:  16249540]

[119]
Chen, J.L.T.; Francis, J. Pyridoxamine, advanced glycation inhibition, and diabetic nephropathy. J. Am. Soc. Nephrol.,  2012, 23(1), 6-8.
 [http://dx.doi.org/10.1681/ASN.2011111097] [PMID:  22158434]

[120]
Kanda, H.; Yamawaki, K. Bardoxolone methyl: drug development for diabetic kidney disease. Clin. Exp. Nephrol.,  2020, 24(10), 857-864.
 [http://dx.doi.org/10.1007/s10157-020-01917-5] [PMID:  32594372]

[121]
Herman-Edelstein, M.; Scherzer, P.; Tobar, A.; Levi, M.; Gafter, U. Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy. J. Lipid Res.,  2014, 55(3), 561-572.
 [http://dx.doi.org/10.1194/jlr.P040501] [PMID:  24371263]

[122]
Tsun, J.G.S.; Yung, S.; Chau, M.K.M.; Shiu, S.W.M.; Chan, T.M.; Tan, K.C.B. Cellular cholesterol transport proteins in diabetic nephropathy. PLoS One,  2014, 9(9), e105787.
 [http://dx.doi.org/10.1371/journal.pone.0105787] [PMID:  25181357]

[123]
Ruan, X.; Varghese, Z.; Fernando, R.; Moorhead, J.F. Cytokines regulation of low-density lipoprotein receptor gene transcription in human mesangial cells. Nephrol. Dial. Transplant.,  1998, 13(6), 1391-1397.
 [http://dx.doi.org/10.1093/ndt/13.6.1391] [PMID:  9641167]

[124]
Ruan, X.Z.; Moorhead, J.F.; Fernando, R.; Wheeler, D.C.; Powis, S.H.; Varghese, Z. PPAR agonists protect mesangial cells from interleukin 1beta-induced intracellular lipid accumulation by activating the ABCA1 cholesterol efflux pathway. J. Am. Soc. Nephrol.,  2003, 14(3), 593-600.
 [http://dx.doi.org/10.1097/01.ASN.0000050414.52908.DA] [PMID:  12595494]

[125]
Ling, L.J. Calcium channel blockers. In: Emergency Medicine: A Comprehensive Study Guide; Tintinalli, J.E.; Ruiz, E.; Krome, R.L., Eds.; McGraw-Hill: New York, NY, 1996; pp. 803-805.

[126]
Lip, G.Y.H.; Ferner, R.E. Poisoning with anti-hypertensive drugs: Calcium antagonists. J. Hum. Hypertens.,  1995, 9(3), 155-161.
 [PMID:  7783095]

[127]
Adams, B.D.; Browne, W.T. Amlodipine overdose causes prolonged calcium channel blocker toxicity. Am. J. Emerg. Med.,  1998, 16(5), 527-528.
 [http://dx.doi.org/10.1016/S0735-6757(98)90011-0] [PMID:  9725975]

[128]
Eland, I.A.; Sundström, A.; Velo, G.P.; Andersen, M.; Sturkenboom, M.C.J.M.; Langman, M.J.S.; Stricker, B.H.C.H.; Wiholm, B.; Eland, I.A.; Sundström, A.; Velo, G.P.; Andersen, M.; Sturkenboom, M.C.J.M.; Langman, M.J.S.; Stricker, B.H.C.H.; Wiholm, B. Antihypertensive medication and the risk of acute pancreatitis: The European case-control study on drug-induced acute pancreatitis (EDIP). Scand. J. Gastroenterol.,  2006, 41(12), 1484-1490.
 [http://dx.doi.org/10.1080/00365520600761676] [PMID:  17101581]

[129]
Serreau, R.; Luton, D.; Macher, M.A.; Delezoide, A.L.; Garel, C.; Jacqz-Aigrain, E. Developmental toxicity of the angiotensin II type 1 receptor antagonists during human pregnancy: A report of 10 cases. BJOG,  2005, 112(6), 710-712.
 [http://dx.doi.org/10.1111/j.1471-0528.2004.00525.x] [PMID:  15924524]

[130]
Payen, V.; Chemin, A.; Jonville-Béra, A.P.; Saliba, E.; Cantagrel, S. Fetal toxicity of angiotensin-II receptor antagonists. J. Gynecol. Obstet. Biol. Reprod. (Paris),  2006, 35(7), 729-731.
 [http://dx.doi.org/10.1016/S0368-2315(06)76471-7] [PMID:  17088776]

[131]
Simonetti, G.D.; Baumann, T.; Pachlopnik, J.M.; von Vigier, R.O.; Bianchetti, M.G. Non-lethal fetal toxicity of the angiotensin receptor blocker candesartan. Pediatr. Nephrol.,  2006, 21(9), 1329-1330.
 [http://dx.doi.org/10.1007/s00467-006-0162-y] [PMID:  16807764]

[132]
Roger, N.; Popovic, I.; Madelenat, P.; Mahieu-Caputo, D. Fetal toxicity of angiotensin-II-receptor inhibitors. Case report. Gynécol. Obstét. Fertil.,  2007, 35(6), 556-560.
 [http://dx.doi.org/10.1016/j.gyobfe.2007.03.015] [PMID:  17544313]

[133]
Wang, G.S.; Hoyte, C. Review of biguanide (metformin) toxicity. J. Intensive Care Med.,  2019, 34(11-12), 863-876.
 [http://dx.doi.org/10.1177/0885066618793385] [PMID:  30126348]

[134]
Perrone, J.; Phillips, C.; Gaieski, D. Occult metformin toxicity in three patients with profound lactic acidosis. J. Emerg. Med.,  2011, 40(3), 271-275.
 [http://dx.doi.org/10.1016/j.jemermed.2007.11.055] [PMID:  18571361]

[135]
Shadnia, S.; Barzi, F.; Askari, A.; Hassanian-Moghaddam, H.; Zamani, N.; Ebrahimian, K. Metformin toxicity: A report of 204 cases from Iran. Curr. Drug Saf.,  2013, 8(4), 278-281.
 [http://dx.doi.org/10.2174/1574210195346398863] [PMID:  24070002]

[136]
Mallick, S. Metformin induced acute pancreatitis precipitated by renal failure. Postgrad. Med. J.,  2004, 80(942), 239-240.
 [http://dx.doi.org/10.1136/pgmj.2003.011957] [PMID:  15082849]

[137]
Scheen, A.J. Thiazolidinediones and liver toxicity. Diabetes Metab.,  2001, 27(3), 305-313.
 [PMID:  11431595]

[138]
Famularo, G.; Gasbarrone, L.; Minisola, G. Pancreatitis during treatment with liraglutide. JOP,  2012, 13(5), 540-541.
 [PMID:  22964963]

[139]
Maor, Y.; Ergaz, D.; Malnick, S.D.H.; Melzer, E.; Neuman, M.G. Liraglutide-induced hepatotoxicity. Biomedicines,  2021, 9(2), 106.
 [http://dx.doi.org/10.3390/biomedicines9020106] [PMID:  33498980]

[140]
Denker, P.S.; Dimarco, P.E. Exenatide (exendin-4)-induced pancreatitis: A case report. Diabetes Care,  2006, 29(2), 471.
 [http://dx.doi.org/10.2337/diacare.29.02.06.dc05-2043] [PMID:  16443920]

[141]
McGill, J.B.; King, G.L.; Berg, P.H.; Price, K.L.; Kles, K.A.; Bastyr, E.J.; Hyslop, D.L. Clinical safety of the selective PKC-β inhibitor, ruboxistaurin. Expert Opin. Drug Saf.,  2006, 5(6), 835-845.
 [http://dx.doi.org/10.1517/14740338.5.6.835] [PMID:  17044810]

[142]
Waanders, F.; van Goor, H.; Navis, G. Adverse renal effects of the AGE inhibitor pyridoxamine in combination with ACEi in non-diabetic adriamycin-induced renal damage in rats. Kidney Blood Press. Res.,  2008, 31(5), 350-359.
 [http://dx.doi.org/10.1159/000173253] [PMID:  19018148]

[143]
Dabeek, W.M.; Marra, M.V. Dietary quercetin and kaempferol: Bioavailability and potential cardiovascular-related bioactivity in humans. Nutrients,  2019, 11(10), 2288.
 [http://dx.doi.org/10.3390/nu11102288] [PMID:  31557798]

[144]
Lu, N.T.; Crespi, C.M.; Liu, N.M.; Vu, J.Q.; Ahmadieh, Y.; Wu, S.; Lin, S.; McClune, A.; Durazo, F.; Saab, S.; Han, S.; Neiman, D.C.; Beaven, S.; French, S.W. A phase I dose escalation study demonstrates quercetin safety and explores potential for bioflavonoid antivirals in patients with chronic hepatitis C. Phytother. Res.,  2016, 30(1), 160-168.
 [http://dx.doi.org/10.1002/ptr.5518] [PMID:  26621580]

[145]
Vivarelli, S.; Salemi, R.; Candido, S.; Falzone, L.; Santagati, M.; Stefani, S.; Torino, F.; Banna, G.L.; Tonini, G.; Libra, M. Gut microbiota and cancer: From pathogenesis to therapy. Cancers,  2019, 11(1), 38.
 [http://dx.doi.org/10.3390/cancers11010038] [PMID:  30609850]

[146]
Gubert, C.; Kong, G.; Renoir, T.; Hannan, A.J. Exercise, diet and stress as modulators of gut microbiota: Implications for neurodegenerative diseases. Neurobiol. Dis.,  2020, 134, 104621.
 [http://dx.doi.org/10.1016/j.nbd.2019.104621] [PMID:  31628992]

[147]
Fung, T.C.; Olson, C.A.; Hsiao, E.Y. Interactions between the microbiota, immune and nervous systems in health and disease. Nat. Neurosci.,  2017, 20(2), 145-155.
 [http://dx.doi.org/10.1038/nn.4476] [PMID:  28092661]

[148]
Witkowski, M.; Weeks, T.L.; Hazen, S.L. Gut microbiota and cardiovascular disease. Circ. Res.,  2020, 127(4), 553-570.
 [http://dx.doi.org/10.1161/CIRCRESAHA.120.316242] [PMID:  32762536]

[149]
Nagase, N.; Ikeda, Y.; Tsuji, A.; Kitagishi, Y.; Matsuda, S. Efficacy of probiotics on the modulation of gut microbiota in the treatment of diabetic nephropathy. World J. Diabetes,  2022, 13(3), 150-160.
 [http://dx.doi.org/10.4239/wjd.v13.i3.150] [PMID:  35432750]

[150]
Chen, W.; Zhang, M.; Guo, Y.; Wang, Z.; Liu, Q.; Yan, R.; Wang, Y.; Wu, Q.; Yuan, K.; Sun, W. The profile and function of gut microbiota in diabetic nephropathy. Diabetes Metab. Syndr. Obes.,  2021, 14, 4283-4296.
 [http://dx.doi.org/10.2147/DMSO.S320169] [PMID:  34703261]

[151]
Zaky, A.; Glastras, S.J.; Wong, M.Y.W.; Pollock, C.A.; Saad, S. The role of the gut microbiome in diabetes and obesity-related kidney disease. Int. J. Mol. Sci.,  2021, 22(17), 9641.
 [http://dx.doi.org/10.3390/ijms22179641] [PMID:  34502562]

[152]
Patcharatrakul, T.; Gonlachanvit, S. Chili peppers, curcumins, and prebiotics in gastrointestinal health and disease. Curr. Gastroenterol. Rep.,  2016, 18(4), 19.
 [http://dx.doi.org/10.1007/s11894-016-0494-0] [PMID:  26973345]

[153]
Nissen, L.; Valerii, M.C.; Spisni, E.; Casciano, F.; Gianotti, A. multiunit in vitro Colon model for the evaluation of prebiotic potential of a fiber plus D- Limonene food supplement. Foods,  2021, 10(10), 2371.
 [http://dx.doi.org/10.3390/foods10102371] [PMID:  34681420]

[154]
Parkar, S.G.; Stevenson, D.E.; Skinner, M.A. The potential influence of fruit polyphenols on colonic microflora and human gut health. Int. J. Food Microbiol.,  2008, 124(3), 295-298.
 [http://dx.doi.org/10.1016/j.ijfoodmicro.2008.03.017] [PMID:  18456359]

[155]
Zhang, Z.B.; Luo, D.D.; Xie, J.H.; Xian, Y.F.; Lai, Z.Q.; Liu, Y.H.; Liu, W.H.; Chen, J.N.; Lai, X.P.; Lin, Z.X.; Su, Z.R. Curcumin’s metabolites, tetrahydrocurcumin and octahydrocurcumin, possess superior anti-inflammatory effects in vivo through suppression of TAK1-NF-κB pathway. Front. Pharmacol.,  2018, 9, 1181.
 [http://dx.doi.org/10.3389/fphar.2018.01181] [PMID:  30386242]

[156]
Jarret, R.L.; Barboza, G.E.; Costa Batista, F.R.; Berke, T.; Chou, Y.Y.; Hulse-Kemp, A.; Ochoa-Alejo, N.; Tripodi, P.; Veres, A.; Garcia, C.C.; Csillery, G.; Huang, Y.K.; Kiss, E.; Kovacs, Z.; Kondrak, M.; Arce-Rodriguez, M.L.; Scaldaferro, M.A.; Szoke, A. Capsicum - An abbreviated compendium. J. Am. Soc. Hortic. Sci.,  2019, 144(1), 3-22.
 [http://dx.doi.org/10.21273/JASHS04446-18]

[157]
Guala, G. Integrated Taxonomic Information System (ITIS).  Available from:
          https://www.itis.gov/ (Accessed Oct-2022). 

[158]
Aranha, B.C.; Hoffmann, J.F.; Barbieri, R.L.; Rombaldi, C.V.; Chaves, F.C. Untargeted metabolomic analysis of Capsicum spp. by GC–MS. Phytochem. Anal.,  2017, 28(5), 439-447.
 [http://dx.doi.org/10.1002/pca.2692] [PMID:  28497560]

[159]
Saito, A.; Yamamoto, M. Acute oral toxicity of capsaicin in mice and rats. J. Toxicol. Sci.,  1996, 21(3), 195-200.
 [http://dx.doi.org/10.2131/jts.21.3_195] [PMID:  8887888]

[160]
Reyes-Escogido, M.; Gonzalez-Mondragon, E.G.; Vazquez-Tzompantzi, E. Chemical and pharmacological aspects of capsaicin. Molecules,  2011, 16(2), 1253-1270.
 [http://dx.doi.org/10.3390/molecules16021253] [PMID:  21278678]

[161]
Li, J.; Wang, D.H. Increased GFR and renal excretory function by activation of TRPV1 in the isolated perfused kidney. Pharmacol. Res.,  2008, 57(3), 239-246.
 [http://dx.doi.org/10.1016/j.phrs.2008.01.011] [PMID:  18329285]

[162]
Suri, A.; Szallasi, A. The emerging role of TRPV1 in diabetes and obesity. Trends Pharmacol. Sci.,  2008, 29(1), 29-36.
 [http://dx.doi.org/10.1016/j.tips.2007.10.016] [PMID:  18055025]

[163]
Caballero, J. A new era for the design of TRPV1 antagonists and agonists with the use of structural information and molecular docking of capsaicin-like compounds. J. Enzyme Inhib. Med. Chem.,  2022, 37(1), 2169-2178.
 [http://dx.doi.org/10.1080/14756366.2022.2110089] [PMID:  35975286]

[164]
Darré, L.; Domene, C. Binding of capsaicin to the TRPV1 ion channel. Mol. Pharm.,  2015, 12(12), 4454-4465.
 [http://dx.doi.org/10.1021/acs.molpharmaceut.5b00641] [PMID:  26502196]

[165]
Backes, T.M.; Rössler, O.G.; Hui, X.; Grötzinger, C.; Lipp, P.; Thiel, G. Stimulation of TRPV1 channels activates the AP-1 transcription factor. Biochem. Pharmacol.,  2018, 150, 160-169.
 [http://dx.doi.org/10.1016/j.bcp.2018.02.008] [PMID:  29452097]

[166]
Luo, Z.; Ma, L.; Zhao, Z.; He, H.; Yang, D.; Feng, X.; Ma, S.; Chen, X.; Zhu, T.; Cao, T.; Liu, D.; Nilius, B.; Huang, Y.; Yan, Z.; Zhu, Z. TRPV1 activation improves exercise endurance and energy metabolism through PGC-1&#945; upregulation in mice. Cell Res.,  2012, 22(3), 551-564.
 [http://dx.doi.org/10.1038/cr.2011.205] [PMID:  22184011]

[167]
Wei, X.; Wei, X.; Lu, Z.; Li, L.; Hu, Y.; Sun, F.; Jiang, Y.; Ma, H.; Zheng, H.; Yang, G.; Liu, D.; Gao, P.; Zhu, Z. Activation of TRPV1 channel antagonizes diabetic nephropathy through inhibiting endoplasmic reticulum-mitochondria contact in podocytes. Metabolism,  2020, 105, 154182.
 [http://dx.doi.org/10.1016/j.metabol.2020.154182] [PMID:  32061660]

[168]
Hazarika, T.K. Citrus genetic diversity of north-east India, their distribution, ecogeography and ecobiology. Genet. Resour. Crop Evol.,  2012, 59(6), 1267-1280.
 [http://dx.doi.org/10.1007/s10722-012-9846-2]

[169]
Sadka, A.; Shlizerman, L.; Kamara, I.; Blumwald, E. Primary metabolism in citrus fruit as affected by its unique structure. Front. Plant Sci.,  2019, 10(10), 1167.
 [http://dx.doi.org/10.3389/fpls.2019.01167] [PMID:  31611894]

[170]
Dugo, G.; Di Giacomo, A. Eds.; Citrus: the genus citrus; CRC Press, 2002. 
 [http://dx.doi.org/10.1201/9780203216613]

[171]
Champagne, D.E.; Koul, O.; Isman, M.B.; Scudder, G.G.E.; Neil Towers, G.H. Biological activity of limonoids from the rutales. Phytochemistry,  1992, 31(2), 377-394.
 [http://dx.doi.org/10.1016/0031-9422(92)90003-9]

[172]
Reinhard, H.; Sager, F.; Zoller, O. Citrus juice classification by SPME-GC-MS and electronic nose measurements. Lebensm. Wiss. Technol.,  2008, 41(10), 1906-1912.
 [http://dx.doi.org/10.1016/j.lwt.2007.11.012]

[173]
Brendel, R.; Schwolow, S.; Rohn, S.; Weller, P. Volatilomic profiling of citrus juices by dual-detection HS-GC-MS-IMS and machine learning - An alternative authentication approach. J. Agric. Food Chem.,  2021, 69(5), 1727-1738.
 [http://dx.doi.org/10.1021/acs.jafc.0c07447] [PMID:  33527826]

[174]
Surendran, S.; Qassadi, F.; Surendran, G.; Lilley, D.; Heinrich, M. Myrcene - what are the potential health benefits of this flavouring and aroma agent? Front. Nutr.,  2021, 8(699666), 699666.
 [http://dx.doi.org/10.3389/fnut.2021.699666] [PMID:  34350208]

[175]
Jiang, M.H.; Yang, L.; Zhu, L.; Piao, J.H.; Jiang, J.G. Comparative GC/MS analysis of essential oils extracted by 3 methods from the bud of Citrus aurantium L. var. amara Engl. J. Food Sci.,  2011, 76(9), C1219-C1225.
 [http://dx.doi.org/10.1111/j.1750-3841.2011.02421.x] [PMID:  22416680]

[176]
Smith, D.C.; Forland, S.; Bachanos, E.; Matejka, M.; Barrett, V. Qualitative analysis of citrus fruit extracts by GC/MS: An undergraduate experiment. Chem. Educ.,  2001, 6(1), 28-31.
 [http://dx.doi.org/10.1007/s00897000450a]

[177]
Benavente-García, O.; Castillo, J.; Marin, F.R.; Ortuño, A.; Del Río, J.A. Uses and properties of citrus flavonoids. J. Agric. Food Chem.,  1997, 45(12), 4505-4515.
 [http://dx.doi.org/10.1021/jf970373s] [PMID:  18593176]

[178]
Kurogi, Y. Mesangial cell proliferation inhibitors for the treatment of proliferative glomerular disease. Med. Res. Rev.,  2003, 23(1), 15-31.
 [http://dx.doi.org/10.1002/med.10028] [PMID:  12424751]

[179]
Yan, N.; Wen, L.; Peng, R.; Li, H.; Liu, H.; Peng, H.; Sun, Y.; Wu, T.; Chen, L.; Duan, Q.; Sun, Y.; Zhou, Q.; Wei, L.; Zhang, Z. Naringenin ameliorated kidney injury through Let-7a/TGFBR1 signaling in diabetic nephropathy. J. Diabetes Res.,  2016, 2016, 1-13.
 [http://dx.doi.org/10.1155/2016/8738760] [PMID:  27446963]

[180]
Ortiz-Andrade, R.R.; Sánchez-Salgado, J.C.; Navarrete-Vázquez, G.; Webster, S.P.; Binnie, M.; García-Jiménez, S.; León-Rivera, I.; Cigarroa-Vázquez, P.; Villalobos-Molina, R.; Estrada-Soto, S. Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulation. Diabetes Obes. Metab.,  2008, 10(11), 1097-1104.
 [http://dx.doi.org/10.1111/j.1463-1326.2008.00869.x] [PMID:  18355329]

[181]
Bickers, D.; Calow, P.; Greim, H.; Hanifin, J.M.; Rogers, A.E.; Saurat, J.H.; Sipes, I.G.; Smith, R.L.; Tagami, H. A toxicologic and dermatologic assessment of linalool and related esters when used as fragrance ingredients. Food Chem. Toxicol.,  2003, 41(7), 919-942.
 [http://dx.doi.org/10.1016/S0278-6915(03)00016-4] [PMID:  12804649]

[182]
Deepa, B.; Venkatraman, C. Effects of linalool on inflammation, matrix accumulation and podocyte loss in kidney of streptozotocin-induced diabetic rats. Toxicol. Mech. Methods,  2013, 23(4), 223-234.
 [http://dx.doi.org/10.3109/15376516.2012.743638] [PMID:  23193997]

[183]
Aaltonen, P.; Luimula, P.; Åström, E.; Palmen, T.; Grönholm, T.; Palojoki, E.; Jaakkola, I.; Ahola, H.; Tikkanen, I.; Holthöfer, H. Changes in the expression of nephrin gene and protein in experimental diabetic nephropathy. Lab. Invest.,  2001, 81(9), 1185-1190.
 [http://dx.doi.org/10.1038/labinvest.3780332] [PMID:  11555666]

[184]
Deepa, B.; Anuradha, C.V. Linalool, a plant derived monoterpene alcohol, rescues kidney from diabetes-induced nephropathic changes via blood glucose reduction. Diabetol. Croat.,  2011, 40(4), 121-138.

[185]
Forbes, J.M.; Coughlan, M.T.; Cooper, M.E. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes,  2008, 57(6), 1446-1454.
 [http://dx.doi.org/10.2337/db08-0057] [PMID:  18511445]

[186]
Baud, L.; Ardaillou, R. Reactive oxygen species: Production and role in the kidney. Am. J. Physiol.,  1986, 251(5 Pt 2), F765-F776.
 [PMID:  3022602]

[187]
Sedeek, M.; Nasrallah, R.; Touyz, R.M.; Hébert, R.L. NADPH oxidases, reactive oxygen species, and the kidney: friend and foe. J. Am. Soc. Nephrol.,  2013, 24(10), 1512-1518.
 [http://dx.doi.org/10.1681/ASN.2012111112] [PMID:  23970124]

[188]
Yan, L. Redox imbalance stress in diabetes mellitus: Role of the polyol pathway. Animal Model. Exp. Med.,  2018, 1(1), 7-13.
 [http://dx.doi.org/10.1002/ame2.12001] [PMID:  29863179]

[189]
Van Nguyen, C. Toxicity of the AGEs generated from the Maillard reaction: On the relationship of food-AGEs and biological-AGEs. Mol. Nutr. Food Res.,  2006, 50(12), 1140-1149.
 [http://dx.doi.org/10.1002/mnfr.200600144] [PMID:  17131455]

[190]
Makino, H.; Shikata, K.; Hironaka, K.; Kushiro, M.; Yamasaki, Y.; Sugimoto, H.; Ota, Z.; Araki, N.; Horiuchi, S. Ultrastructure of nonenzymatically glycated mesangial matrix in diabetic nephropathy. Kidney Int.,  1995, 48(2), 517-526.
 [http://dx.doi.org/10.1038/ki.1995.322] [PMID:  7564121]

[191]
Kummer, R.; Fachini-Queiroz, F.C.; Estevão-Silva, C.F.; Grespan, R.; Silva, E.L.; Bersani-Amado, C.A.; Cuman, R.K. Evaluation of anti-inflammatory activity of Citrus latifolia Tanaka essential oil and limonene in experimental mouse models. Evid. based Complement. Altern. Med.,  2013, 2013, 859083.

[192]
Delort, E.; Jaquier, A.; Decorzant, E.; Chapuis, C.; Casilli, A.; Frérot, E. Comparative analysis of three Australian finger lime (Citrus australasica) cultivars: Identification of unique citrus chemotypes and new volatile molecules. Phytochemistry,  2015, 109, 111-124.
 [http://dx.doi.org/10.1016/j.phytochem.2014.10.023] [PMID:  25468539]

[193]
Joglekar, M.M.; Panaskar, S.N.; Chougale, A.D.; Kulkarni, M.J.; Arvindekar, A.U. A novel mechanism for antiglycative action of limonene through stabilization of protein conformation. Mol. Biosyst.,  2013, 9(10), 2463-2472.
 [http://dx.doi.org/10.1039/c3mb00020f] [PMID:  23872839]

[194]
Chaturvedi, S.K.; Ahmad, E.; Khan, J.M.; Alam, P.; Ishtikhar, M.; Khan, R.H. Elucidating the interaction of limonene with bovine serum albumin: a multi-technique approach. Mol. Biosyst.,  2015, 11(1), 307-316.
 [http://dx.doi.org/10.1039/C4MB00548A] [PMID:  25382435]

[195]
Panaskar, S.N.; Joglekar, M.M.; Taklikar, S.S.; Haldavnekar, V.S.; Arvindekar, A.U. Aegle marmelos Correa leaf extract prevents secondary complications in streptozotocin-induced diabetic rats and demonstration of limonene as a potent antiglycating agent. J. Pharm. Pharmacol.,  2013, 65(6), 884-894.
 [http://dx.doi.org/10.1111/jphp.12044] [PMID:  23647682]

[196]
Yoon, W.J.; Lee, N.H.; Hyun, C.G. Limonene suppresses lipopolysaccharide-induced production of nitric oxide, prostaglandin E2, and pro-inflammatory cytokines in RAW 264.7 macrophages. J. Oleo Sci.,  2010, 59(8), 415-421.
 [http://dx.doi.org/10.5650/jos.59.415] [PMID:  20625233]

[197]
Iwanage, Y. Studies on d-limonene, as gallstone solubilizer. II. Acute and subacute toxicities. Oyo Yakuri,  1975, 9, 387-401.

[198]
Kumar, J.; Verma, V.; Goyal, A.; Shahi, A.K.; Sparoo, R.; Sangwan, R.S.; Qazi, G.N. Genetic diversity analysis in Cymbopogon species using DNA markers. Plant Omics,  2009, 2(1), 20.

[199]
Ganjewala, D. Cymbopogon essential oils: Chemical compositions and bioactivities. Int. J. Essent. Oil Res,  2009, 3(2-3), 56-65.

[200]
Ilayperuma, I. Effects of intraperitoneal administration of Citral on male reproductive organs in the rat. Galen Med. J.,  2009, 13(1), 29-32.
 [http://dx.doi.org/10.4038/gmj.v13i1.891]

[201]
Babukumar, S.; Vinothkumar, V.; Sankaranarayanan, C.; Srinivasan, S. Geraniol, a natural monoterpene, ameliorates hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Pharm. Biol.,  2017, 55(1), 1442-1449.
 [http://dx.doi.org/10.1080/13880209.2017.1301494] [PMID:  28330423]

[202]
Kpoviessi, S.; Bero, J.; Agbani, P.; Gbaguidi, F.; Kpadonou-Kpoviessi, B.; Sinsin, B.; Accrombessi, G.; Frédérich, M.; Moudachirou, M.; Quetin-Leclercq, J. Chemical composition, cytotoxicity and in vitro antitrypanosomal and antiplasmodial activity of the essential oils of four Cymbopogon species from Benin. J. Ethnopharmacol.,  2014, 151(1), 652-659.
 [http://dx.doi.org/10.1016/j.jep.2013.11.027] [PMID:  24269775]

[203]
Robbins, S.R.J. Selected markets for the essential oils of lemongrass, citronella and eucalyptus. Tropical Products Institute Report,  1983, 17, 13.

[204]
Mishra, C.; Khalid, M.A.; Tripathi, D.; Mahdi, A.A. Comparative anti-diabetic study of three phytochemicals on high-fat diet and streptozotocin-induced diabetic dyslipidemic rats. Int. J. Biomed. Adv. Res.,  2018, 9(8), 8.

[205]
Katsukawa, M.; Nakata, R.; Takizawa, Y.; Hori, K.; Takahashi, S.; Inoue, H. Citral, a component of lemongrass oil, activates PPARα and γ and suppresses COX-2 expression. Biochim. Biophys. Acta Mol. Cell Biol. Lipids,  2010, 1801(11), 1214-1220.
 [http://dx.doi.org/10.1016/j.bbalip.2010.07.004] [PMID:  20656057]

[206]
Sforcin, J.M.; Amaral, J.T.; Fernandes, A., Jr; Sousa, J.P.B.; Bastos, J.K. Lemongrass effects on IL-1β and IL-6 production by macrophages. Nat. Prod. Res.,  2009, 23(12), 1151-1159.
 [http://dx.doi.org/10.1080/14786410902800681] [PMID:  19662581]

[207]
Zarandi, M.H.; Sharifiyazdi, H.; Nazifi, S.; Ghaemi, M.; Bakhtyari, M.K. Effects of citral on serum inflammatory factors and liver gene expression of IL-6 and TNF-alpha in experimental diabetes. Comp. Clin. Pathol.,  2021, 30(3), 351-361.
 [http://dx.doi.org/10.1007/s00580-021-03205-4]

[208]
Lee, H.J.; Jeong, H.S.; Kim, D.J.; Noh, Y.H.; Yuk, D.Y.; Hong, J.T. Inhibitory effect of citral on NO production by suppression of iNOS expression and NF-κB activation in RAW264.7 cells. Arch. Pharm. Res.,  2008, 31(3), 342-349.
 [http://dx.doi.org/10.1007/s12272-001-1162-0] [PMID:  18409048]

[209]
El-Said, Y.A.M.; Sallam, N.A.A.; Ain-Shoka, A.A.M.; Abdel-Latif, H.A.T. Geraniol ameliorates diabetic nephropathy via interference with miRNA-21/PTEN/Akt/mTORC1 pathway in rats. Naunyn Schmiedebergs Arch. Pharmacol.,  2020, 393(12), 2325-2337.
 [http://dx.doi.org/10.1007/s00210-020-01944-9] [PMID:  32666288]

[210]
Shah, G.; Shri, R.; Panchal, V.; Sharma, N.; Singh, B.; Mann, A.S. Scientific basis for the therapeutic use of Cymbopogon citratus, stapf (Lemon grass). J. Adv. Pharm. Technol. Res.,  2011, 2(1), 3-8.
 [http://dx.doi.org/10.4103/2231-4040.79796] [PMID:  22171285]

[211]
Rauter, A.P.; Lopes, R.G.; Martins, A. CGlycosylflavonoids: Identification, bioactivity and synthesis. Nat. Prod. Commun.,  2007, 2(11), 1934578X0700201125.

[212]
Figueirinha, A.; Paranhos, A.; Pérez-Alonso, J.J.; Santos-Buelga, C.; Batista, M.T. Cymbopogon citratus leaves: Characterization of flavonoids by HPLC–PDA–ESI/MS/MS and an approach to their potential as a source of bioactive polyphenols. Food Chem.,  2008, 110(3), 718-728.
 [http://dx.doi.org/10.1016/j.foodchem.2008.02.045]

[213]
Fonseca-Silva, F.; Inacio, J.D.F.; Canto-Cavalheiro, M.M.; Menna-Barreto, R.F.S.; Almeida-Amaral, E.E. Oral efficacy of apigenin against cutaneous leishmaniasis: Involvement of reactive oxygen species and autophagy as a mechanism of action. PLoS Negl. Trop. Dis.,  2016, 10(2), e0004442.
 [http://dx.doi.org/10.1371/journal.pntd.0004442] [PMID:  26862901]

[214]
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.
 [http://dx.doi.org/10.1152/ajprenal.00393.2016] [PMID:  28566504]

[215]
Xu, Y.; Zhang, J.; Fan, L.; He, X. miR-423-5p suppresses high-glucose-induced podocyte injury by targeting Nox4. Biochem. Biophys. Res. Commun.,  2018, 505(2), 339-345.
 [http://dx.doi.org/10.1016/j.bbrc.2018.09.067] [PMID:  30245133]

[216]
Hou, Y.; Zhang, Y.; Lin, S.; Yu, Y.; Yang, L.; Li, L.; Wang, W. Protective mechanism of apigenin in diabetic nephropathy is related to its regulation of miR-423-5P-USF2 axis. Am. J. Transl. Res.,  2021, 13(4), 2006-2020.
 [PMID:  34017372]

[217]
Hossain, C.M.; Ghosh, M.K.; Satapathy, B.S.; Dey, N.S.; Mukherjee, B. Apigenin causes biochemical modulation, GLUT4 and Cd38 alterations to improve diabetes and to protect damages of some vital organs in experimental diabetes. Am. J. Pharmacol. Toxicol.,  2014, 9(1), 39-52.
 [http://dx.doi.org/10.3844/ajptsp.2014.39.52]

[218]
DeRango-Adem, E.F.; Blay, J. Does oral apigenin have real potential for a therapeutic effect in the context of human gastrointestinal and other cancers? Front. Pharmacol.,  2021, 12, 681477.
 [http://dx.doi.org/10.3389/fphar.2021.681477] [PMID:  34084146]

[219]
Mukherjee, B.; Banerjee, S.; Mondal, L.; Chakraborty, S.; Chanda, D.; Perera, J.A. Bioactive flavonoid apigenin and its nanoformulations: a promising hope for diabetes and cancer. In: Nanomedicine for Bioactives; Springer: Singapore, 2020; pp. 367-382.
 [http://dx.doi.org/10.1007/978-981-15-1664-1_13]

[220]
Chakrovorty, A.; Bhattacharjee, B.; Dey, R.; Samadder, A.; Nandi, S. Graphene: the magic carbon derived biological weapon for human welfare. Int. Acad. Publ. House,  2021, 25, 9-17.
 [http://dx.doi.org/10.52756/ijerr.2021.v25.002]

[221]
Syamkumar, S.; Sasikumar, B. Molecular marker based genetic diversity analysis of curcuma species from India. Sci. Hortic.,  2007, 112(2), 235-241.
 [http://dx.doi.org/10.1016/j.scienta.2006.12.021]

[222]
Samadder, A.; Khuda-Bukhsh, A.R. Nanotechnological approaches in diabetes treatment: A new horizon. World J. Transl. Med.,  2014, 3(2), 84-95.
 [http://dx.doi.org/10.5528/wjtm.v3.i2.84]

[223]
Chen, L.; Liu, T.; Wang, Q.; Liu, J. Anti-inflammatory effect of combined tetramethylpyrazine, resveratrol and curcumin in vivo. BMC Complement. Altern. Med.,  2017, 17(1), 233.
 [http://dx.doi.org/10.1186/s12906-017-1739-7] [PMID:  28449676]

[224]
Widyananda, M.H.; Ansori, A.N.; Kharisma, V.D.; Rizky, W.C.; Dings, T.G.; Rebezov, M.; Maksimiuk, N.; Denisenko, A.; Nugraha, A.P. Investigating the potential of curcumin, demethoxycurcumin and bisdemethoxycurcumin as wild-type and mutant her2 inhibitors against various cancer types using bioinformatics analysis. Biochem. Cell. Arch.,  2021, 21(2), 3335-3343.

[225]
Zhang, D.W.; Fu, M.; Gao, S.H.; Liu, J.L. Curcumin and diabetes: A systematic review. Evid.-. Based Complementary Altern.Med,  2013, 2013, 636053.

[226]
Chuengsamarn, S.; Rattanamongkolgul, S.; Luechapudiporn, R.; Phisalaphong, C.; Jirawatnotai, S. Curcumin extract for prevention of type 2 diabetes. Diabetes Care,  2012, 35(11), 2121-2127.
 [http://dx.doi.org/10.2337/dc12-0116] [PMID:  22773702]

[227]
Bisht, S.; Feldmann, G.; Soni, S.; Ravi, R.; Karikar, C.; Maitra, A.; Maitra, A. Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): A novel strategy for human cancer therapy. J. Nanobiotechnology,  2007, 5(1), 3.
 [http://dx.doi.org/10.1186/1477-3155-5-3] [PMID:  17439648]

[228]
Chakrovorty, A.; Bhattacharjee, B.; Saxena, A.; Samadder, A.; Nandi, S. Current naturopathy to combat Alzheimer’s disease. Curr. Neuropharmacol.,  2022, 20, 808-841.
 [http://dx.doi.org/10.2174/1570159X20666220927121022] [PMID:  36173068]

[229]
Tabrizi, R.; Vakili, S.; Akbari, M.; Mirhosseini, N.; Lankarani, K.B.; Rahimi, M.; Mobini, M.; Jafarnejad, S.; Vahedpoor, Z.; Asemi, Z. The effects of curcumin-containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials. Phytother. Res.,  2019, 33(2), 253-262.
 [http://dx.doi.org/10.1002/ptr.6226] [PMID:  30402990]

[230]
He, Y.; Yue, Y.; Zheng, X.; Zhang, K.; Chen, S.; Du, Z. Curcumin, inflammation, and chronic diseases: How are they linked? Molecules,  2015, 20(5), 9183-9213.
 [http://dx.doi.org/10.3390/molecules20059183] [PMID:  26007179]

[231]
Motterlini, R.; Foresti, R.; Bassi, R.; Green, C.J. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic. Biol. Med.,  2000, 28(8), 1303-1312.
 [http://dx.doi.org/10.1016/S0891-5849(00)00294-X] [PMID:  10889462]

[232]
Karlowee, H.; Gumay, A.R. Turmeric as a preventive agent of oxidative stress and diabetic nephropathy in alloxan induced wistar rats. Pak. J. Med. Health Sci.,  2019, 13(4), 1208-1213.

[233]
Nowotny, K.; Jung, T.; Höhn, A.; Weber, D.; Grune, T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules,  2015, 5(1), 194-222.
 [http://dx.doi.org/10.3390/biom5010194] [PMID:  25786107]

[234]
Soetikno, V.; Watanabe, K.; Sari, F.R.; Harima, M.; Thandavarayan, R.A.; Veeraveedu, P.T.; Arozal, W.; Sukumaran, V.; Lakshmanan, A.P.; Arumugam, S.; Suzuki, K. Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats. Mol. Nutr. Food Res.,  2011, 55(11), 1655-1665.
 [http://dx.doi.org/10.1002/mnfr.201100080] [PMID:  22045654]

[235]
Riser, B.L.; Denichilo, M.; Cortes, P.; Baker, C.; Grondin, J.M.; Yee, J.; Narins, R.G. Regulation of connective tissue growth factor activity in cultured rat mesangial cells and its expression in experimental diabetic glomerulosclerosis. J. Am. Soc. Nephrol.,  2000, 11(1), 25-38.
 [http://dx.doi.org/10.1681/ASN.V11125] [PMID:  10616837]

[236]
Huang, J.; Huang, K.; Lan, T.; Xie, X.; Shen, X.; Liu, P.; Huang, H. Curcumin ameliorates diabetic nephropathy by inhibiting the activation of the SphK1-S1P signaling pathway. Mol. Cell. Endocrinol.,  2013, 365(2), 231-240.
 [http://dx.doi.org/10.1016/j.mce.2012.10.024] [PMID:  23127801]

[237]
Yuan, F.; Kolb, R.; Pandey, G.; Li, W.; Sun, L.; Liu, F.; Sutterwala, F.S.; Liu, Y.; Zhang, W. Involvement of the NLRC4-inflammasome in diabetic nephropathy. PLoS One,  2016, 11(10), e0164135.
 [http://dx.doi.org/10.1371/journal.pone.0164135] [PMID:  27706238]

[238]
Lu, M.; Yin, N.; Liu, W.; Cui, X.; Chen, S.; Wang, E. Curcumin ameliorates diabetic nephropathy by suppressing NLRP3 inflammasome signaling. BioMed Res. Int.,  2017, 2017, 1-10.
 [http://dx.doi.org/10.1155/2017/1516985] [PMID:  28194406]

[239]
Zhang, J.; Li, Q.; Zhang, X.; Chen, Y.; Lu, Y.; Wang, X.; Zhang, L.; Wang, T. Bisdemethoxycurcumin alleviates dextran sodium sulfate-induced colitis via inhibiting NLRP3 inflammasome activation and modulating the gut microbiota in mice. Antioxidants,  2022, 11(10), 1994.
 [http://dx.doi.org/10.3390/antiox11101994] [PMID:  36290717]

[240]
Tang, J.; Tan, X.; Huang, X.; Zhang, J.; Chen, L.; Li, A.; Wang, D. Dual targeting of autophagy and NF-κB pathway by PPARγ contributes to the inhibitory effect of demethoxycurcumin on NLRP3 inflammasome priming. Curr. Mol. Pharmacol.,  2021, 14(5), 914-921.
 [http://dx.doi.org/10.2174/1874467214666210301121020] [PMID:  33645492]

[241]
Sun, L.N.; Yang, Z.Y.; Lv, S.S.; Liu, X.C.; Guan, G.J.; Liu, G. Curcumin prevents diabetic nephropathy against inflammatory response via reversing caveolin-1 Tyr14 phosphorylation influenced TLR4 activation. Int. Immunopharmacol.,  2014, 23(1), 236-246.
 [http://dx.doi.org/10.1016/j.intimp.2014.08.023] [PMID:  25196431]

[242]
ALTamimi, J.Z.; AlFaris, N.A.; AL-Farga, A.M.; Alshammari, G.M.; BinMowyna, M.N.; Yahya, M.A. Curcumin reverses diabetic nephropathy in streptozotocin-induced diabetes in rats by inhibition of PKCβ/p66Shc axis and activation of FOXO-3a. J. Nutr. Biochem.,  2021, 87, 108515.
 [http://dx.doi.org/10.1016/j.jnutbio.2020.108515] [PMID:  33017608]

[243]
Meshkibaf, M.H.; Maleknia, M.; Noroozi, S. Effect of curcumin on gene expression and protein level of methionine sulfoxide reductase A (MSRA), SOD, CAT and GPx in Freund’s adjuvant inflammation-induced male rats. J. Inflamm. Res.,  2019, 12, 241-249.
 [http://dx.doi.org/10.2147/JIR.S212577] [PMID:  31564949]

[244]
Nishinaka, T.; Ichijo, Y.; Ito, M.; Kimura, M.; Katsuyama, M.; Iwata, K.; Miura, T.; Terada, T.; Yabe-Nishimura, C. Curcumin activates human glutathione S-transferase P1 expression through antioxidant response element. Toxicol. Lett.,  2007, 170(3), 238-247.
 [http://dx.doi.org/10.1016/j.toxlet.2007.03.011] [PMID:  17449203]

[245]
Kim, B.H.; Lee, E.S.; Choi, R.; Nawaboot, J.; Lee, M.Y.; Lee, E.Y.; Kim, H.S.; Chung, C.H. Protective effects of curcumin on renal oxidative stress and lipid metabolism in a rat model of type 2 diabetic nephropathy. Yonsei Med. J.,  2016, 57(3), 664-673.
 [http://dx.doi.org/10.3349/ymj.2016.57.3.664] [PMID:  26996567]

[246]
Tu, Q.; Li, Y.; Jin, J.; Jiang, X.; Ren, Y.; He, Q. Curcumin alleviates diabetic nephropathy via inhibiting podocyte mesenchymal transdifferentiation and inducing autophagy in rats and MPC5 cells. Pharm. Biol.,  2019, 57(1), 778-786.
 [http://dx.doi.org/10.1080/13880209.2019.1688843] [PMID:  31741405]

[247]
Zhang, M.; Lu, P.; Zhao, F.; Sun, X.; Ma, W.; Tang, J.; Zhang, C.; Ji, H.; Wang, X. Uncovering the molecular mechanisms of Curcumae rhizoma against myocardial fibrosis using network pharmacology and experimental validation. J. Ethnopharmacol.,  2023, 300, 115751.
 [http://dx.doi.org/10.1016/j.jep.2022.115751] [PMID:  36162550]

[248]
de Oliveira Filho, J.G.; de Almeida, M.J.; Sousa, T.L.; dos Santos, D.C.; Egea, M.B. Bioactive Compounds of Turmeric (Curcuma longa L.). In: Bioactive Compounds in Underutilized Vegetables and Legumes. Reference Series in Phytochemistry; Murthy, H.N.; Paek, K.Y., Eds.; Springer: Cham, 2021. 
 [http://dx.doi.org/10.1007/978-3-030-57415-4_37]

[249]
Ye, M.; Shang, Z-P.; Xu, L-L.; Lu, Y-Y.; Guan, M.; Li, D-Y.; Le, Z-Y.; Bai, Z-L.; Qiao, X. Advances in chemical constituents and quality control of turmeric. World J. Tradit. Chin. Med.,  2019, 5(2), 116.
 [http://dx.doi.org/10.4103/wjtcm.wjtcm_12_19]

[250]
Dong, Y.; Yin, S.; Song, X.; Huo, Y.; Fan, L.; Ye, M.; Hu, H. Involvement of ROS-p38-H2AX axis in novel curcumin analogues-induced apoptosis in breast cancer cells. Mol. Carcinog.,  2016, 55(4), 323-334.
 [http://dx.doi.org/10.1002/mc.22280] [PMID:  25647442]

[251]
Sueth-Santiago, V.; Moraes, J.B.B.; Sobral Alves, E.S.; Vannier-Santos, M.A.; Freire-de-Lima, C.G.; Castro, R.N.; Mendes-Silva, G.P.; Del Cistia, C.N.; Magalhães, L.G.; Andricopulo, A.D.; Sant’Anna, C.M.R.; Decoté-Ricardo, D.; Freire de Lima, M.E. The effectiveness of natural diarylheptanoids against trypanosoma cruzi: Cytotoxicity, ultrastructural alterations and molecular modeling studies. PLoS One,  2016, 11(9), e0162926.
 [http://dx.doi.org/10.1371/journal.pone.0162926] [PMID:  27658305]

[252]
Li, Y.; Toscano, M.; Mazzone, G.; Russo, N. Antioxidant properties and free radical scavenging mechanisms of cyclocurcumin. New J. Chem.,  2018, 42(15), 12698-12705.
 [http://dx.doi.org/10.1039/C8NJ01819G]

[253]
Fu, M.; Chen, L.; Zhang, L.; Yu, X.; Yang, Q. Cyclocurcumin, a curcumin derivative, exhibits immune-modulating ability and is a potential compound for the treatment of rheumatoid arthritis as predicted by the MM-PBSA method. Int. J. Mol. Med.,  2017, 39(5), 1164-1172.
 [http://dx.doi.org/10.3892/ijmm.2017.2926] [PMID:  28339004]

[254]
Zhou, C.X.; Zhang, L.S.; Chen, F.F.; Wu, H.S.; Mo, J.X.; Gan, L.S. Terpenoids from Curcuma wenyujin increased glucose consumption on HepG2 cells. Fitoterapia,  2017, 121, 141-145.
 [http://dx.doi.org/10.1016/j.fitote.2017.06.011] [PMID:  28625730]

[255]
Das, J.M.; Sarma, B.; Nath, N.; Borthakur, M.K. Sustainable prospective of some selected species from moraceae and araceae family of Northeast India: A review. Plant Sci. Today,  2022, 9(2), 312-321.
 [http://dx.doi.org/10.14719/pst.1427]

[256]
Yende, S.; Harle, U.; Rajgure, D.; Tuse, T.; Vyawahare, N. Pharmacological profile of Acorus calamus: an overview. Phcog Rev.,  2008, 2(4), 23.

[257]
Sharma, V.; Sharma, R.; Gautam, D.; Kuca, K.; Nepovimova, E.; Martins, N. Role of Vacha (Acorus calamus Linn.) in neurological and metabolic disorders: evidence from ethnopharmacology, phytochemistry, pharmacology and clinical study. J. Clin. Med.,  2020, 9(4), 1176.
 [http://dx.doi.org/10.3390/jcm9041176] [PMID:  32325895]

[258]
Zhao, Z.F.; Zhou, L.L.; Chen, X.; Cheng, Y.X.; Hou, F.F.; Nie, J. Acortatarin A inhibits high glucose-induced extracellular matrix production in mesangial cells. Chin. Med. J.,  2013, 126(7), 1230-1235.
 [PMID:  23557549]

[259]
Samadder, A.; Dey, S.; Sow, P.; Das, R.; Nandi, S.; Das, J.; Bhattacharjee, B.; Chakrovorty, A.; Biswas, M.; Guptaroy, P. Phyto-chlorophyllin prevents food additive induced genotoxicity and mitochondrial dysfunction via cytochrome c mediated pathway in mice model. Comb. Chem. High Throughput Screen.,  2021, 24(10), 1618-1627.
 [http://dx.doi.org/10.2174/1386207323666201230093510] [PMID:  33380297]

[260]
Das, J.; Samadder, A.; Mondal, J.; Abraham, S.K.; Khuda-Bukhsh, A.R. Nano-encapsulated chlorophyllin significantly delays progression of lung cancer both in in vitro and in vivo models through activation of mitochondrial signaling cascades and drug-DNA interaction. Environ. Toxicol. Pharmacol.,  2016, 46, 147-157.
 [http://dx.doi.org/10.1016/j.etap.2016.07.006] [PMID:  27458703]

[261]
Fahey, J.W.; Stephenson, K.K.; Dinkova-Kostova, A.T.; Egner, P.A.; Kensler, T.W.; Talalay, P. Chlorophyll, chlorophyllin and related tetrapyrroles are significant inducers of mammalian phase 2 cytoprotective genes. Carcinogenesis,  2005, 26(7), 1247-1255.
 [http://dx.doi.org/10.1093/carcin/bgi068] [PMID:  15774490]

[262]
Abouzaid, O. Ameliorating role of chlorophyllin on oxidative stress induced by pirimiphos methyl in erythrocytes and brain of rats. Benha Vet. Med. J.,  2013, 24(1), 141-150.

[263]
Suryavanshi, S.V.; Gharpure, M.; Kulkarni, Y.A. Sodium copper chlorophyllin attenuates adenine-induced chronic kidney disease via suppression of TGF-beta and inflammatory cytokines. Naunyn Schmiedebergs Arch. Pharmacol.,  2020, 393(11), 2029-2041.
 [http://dx.doi.org/10.1007/s00210-020-01912-3] [PMID:  32500189]

[264]
Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: An overview. J. Nutr. Sci.,  2016, 5, e47.
 [http://dx.doi.org/10.1017/jns.2016.41] [PMID:  28620474]

[265]
Kopustinskiene, D.M.; Jakstas, V.; Savickas, A.; Bernatoniene, J. Flavonoids as anticancer agents. Nutrients,  2020, 12(2), 457.
 [http://dx.doi.org/10.3390/nu12020457] [PMID:  32059369]

[266]
Hu, Q.; Qu, C.; Xiao, X.; Zhang, W.; Jiang, Y.; Wu, Z.; Song, D.; Peng, X.; Ma, X.; Zhao, Y. Flavonoids on diabetic nephropathy: Advances and therapeutic opportunities. Chin. Med.,  2021, 16(1), 74.
 [http://dx.doi.org/10.1186/s13020-021-00485-4] [PMID:  34364389]

[267]
Yao, L.H.; Jiang, Y.M.; Shi, J.; Tomás-Barberán, F.A.; Datta, N.; Singanusong, R.; Chen, S.S. Flavonoids in food and their health benefits. Plant Foods Hum. Nutr.,  2004, 59(3), 113-122.
 [http://dx.doi.org/10.1007/s11130-004-0049-7] [PMID:  15678717]

[268]
Amri, J.; Alaee, M.; Babaei, R.; Salemi, Z.; Meshkani, R.; Ghazavi, A.; Akbari, A.; Salehi, M. Biochanin-A has antidiabetic, antihyperlipidemic, antioxidant, and protective effects on diabetic nephropathy via suppression of TGF-β1 and PAR-2 genes expression in kidney tissues of STZ-induced diabetic rats. Biotechnol. Appl. Biochem.,  2022, 69(5), 2112-2121.
 [http://dx.doi.org/10.1002/bab.2272] [PMID:  34652037]

[269]
Ramada, M.M.; Ali, M.A.; Albohy, A.; Zada, S.K.; Tolba, M.F.; Abu-ELElla, D. Molecular modeling studies on biochanin-a as a potential dual inhibitor for VEGFR-2 and Cyclin D1-CDK-4 complex. Arch. Pharm. Sci. Ain Shams Univ,  2021, 5(1), 16-32.

[270]
Sun, M.Y.; Ye, Y.; Xiao, L.; Rahman, K.; Xiad, W.; Zhang, H. Daidzein: A review of pharmacological effects. Afr. J. Tradit. Complement. Altern. Med.,  2016, 13(3), 117-132.
 [http://dx.doi.org/10.21010/ajtcam.v13i3.15]

[271]
Laddha, A.P.; Kulkarni, Y.A. Daidzein attenuates kidney damage in diabetic rats. FASEB J.,  2020, 34(S1), 1.
 [http://dx.doi.org/10.1096/fasebj.2020.34.s1.05292]

[272]
Laddha, A.P.; Murugesan, S.; Kulkarni, Y.A. In-vivo and in-silico toxicity studies of daidzein: an isoflavone from soy. Drug Chem. Toxicol.,  2022, 45(3), 1408-1416.
 [http://dx.doi.org/10.1080/01480545.2020.1833906] [PMID:  33059469]

[273]
Katyal, T.; Garg, A.; Budhiraja, R. Combination of daidzein, hemin and bms182874 halts the progression of diabetes-induced experimental nephropathy. Endocr. Metab. Immune Disord. Drug Targets,  2013, 13(2), 152-162.
 [http://dx.doi.org/10.2174/1871530311313020003] [PMID:  23701217]

[274]
Qian, Y.; Guan, T.; Huang, M.; Cao, L.; Li, Y.; Cheng, H.; Jin, H.; Yu, D. Neuroprotection by the soy isoflavone, genistein, via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model. Neurochem. Int.,  2012, 60(8), 759-767.
 [http://dx.doi.org/10.1016/j.neuint.2012.03.011] [PMID:  22490611]

[275]
Elmarakby, A.A.; Ibrahim, A.S.; Faulkner, J.; Mozaffari, M.S.; Liou, G.I.; Abdelsayed, R. Tyrosine kinase inhibitor, genistein, reduces renal inflammation and injury in streptozotocin-induced diabetic mice. Vascul. Pharmacol.,  2011, 55(5-6), 149-156.
 [http://dx.doi.org/10.1016/j.vph.2011.07.007] [PMID:  21807121]

[276]
Kim, M.J.; Lim, Y. Protective effect of short-term genistein supplementation on the early stage in diabetes-induced renal damage. Mediators Inflamm.,  2013, 2013, 1-14.
 [http://dx.doi.org/10.1155/2013/510212] [PMID:  23737649]

[277]
Wang, Y.; Li, Y.; Zhang, T.; Chi, Y.; Liu, M.; Liu, Y. Genistein and myd88 activate autophagy in high glucose-induced renal podocytes in vitro. Med. Sci. Monit.,  2018, 24, 4823-4831.
 [http://dx.doi.org/10.12659/MSM.910868] [PMID:  29999001]

[278]
Xiong, C.; Wu, Q.; Fang, M.; Li, H.; Chen, B.; Chi, T. Protective effects of luteolin on nephrotoxicity induced by long-term hyperglycaemia in rats. Int. J. Med. Res.,  2020, 202048(4), 0300060520903642.

[279]
Zhang, M.; He, L.; Liu, J.; Zhou, L. Luteolin attenuates diabetic nephropathy through suppressing inflammatory response and oxidative stress by inhibiting STAT3 pathway. Exp. Clin. Endocrinol. Diabetes,  2021, 129(10), 729-739.
 [http://dx.doi.org/10.1055/a-0998-7985] [PMID:  31896157]

[280]
Asuzu, I.U.; Asuzu, I.U. Luteolin isolate from the methanol extract identified as the single-carbon compound responsible for broad antiulcer activities of Cassia singueana Leaves. IOSR J. Pharm.,  2014, 4(10), 17-23.
 [http://dx.doi.org/10.9790/3013-04010017023]

[281]
Das, S.; Das, J.; Samadder, A.; Paul, A.; Khuda-Bukhsh, A.R. Strategic formulation of apigenin-loaded PLGA nanoparticles for intracellular trafficking, DNA targeting and improved therapeutic effects in skin melanoma in vitro. Toxicol. Lett.,  2013, 223(2), 124-138.
 [http://dx.doi.org/10.1016/j.toxlet.2013.09.012] [PMID:  24070738]

[282]
Das, S.; Das, J.; Paul, A.; Samadder, A.; Khuda-Bukhsh, A.R. Apigenin, a bioactive flavonoid from Lycopodium clavatum, stimulates nucleotide excision repair genes to protect skin keratinocytes from ultraviolet B-induced reactive oxygen species and DNA damage. J. Acupunct. Meridian Stud.,  2013, 6(5), 252-262.
 [http://dx.doi.org/10.1016/j.jams.2013.07.002] [PMID:  24139463]

[283]
Das, S.; Das, J.; Samadder, A.; Paul, A.; Khuda-Bukhsh, A.R. Efficacy of PLGA-loaded apigenin nanoparticles in Benzo[a]pyrene and ultraviolet-B induced skin cancer of mice: Mitochondria mediated apoptotic signalling cascades. Food Chem. Toxicol.,  2013, 62, 670-680.
 [http://dx.doi.org/10.1016/j.fct.2013.09.037] [PMID:  24120900]

[284]
Harishkumar, R.; Reddy, L.P.K.; Karadkar, S.H.; Murad, M.A.; Karthik, S.S.; Manigandan, S.; Selvaraj, C.I.; Christopher, J.G. Toxicity and selective biochemical assessment of quercetin, gallic acid, and curcumin in zebrafish. Biol. Pharm. Bull.,  2019, 42(12), 1969-1976.
 [http://dx.doi.org/10.1248/bpb.b19-00296] [PMID:  31787712]

[285]
Mu, M.; An, P.; Wu, Q.; Shen, X.; Shao, D.; Wang, H.; Zhang, Y.; Zhang, S.; Yao, H.; Min, J.; Wang, F. The dietary flavonoid myricetin regulates iron homeostasis by suppressing hepcidin expression. J. Nutr. Biochem.,  2016, 30, 53-61.
 [http://dx.doi.org/10.1016/j.jnutbio.2015.10.015] [PMID:  27012621]

[286]
Bigoniya, P.; Singh, C.S.; Shrivastava, B. In vivo and in vitro hepatoprotective potential of kaempferol, a flavone glycoside from Capparis spinosa. Int. J. Pharm. Biol. Sci.,  2013, 3(4), 139-152.

[287]
Samadder, A.; Tarafdar, D.; Das, R.; Khuda-Bukhsh, A.R.; Abraham, S.K. Efficacy of nanoencapsulated pelargonidin in ameliorating pesticide toxicity in fish and L6 cells: Modulation of oxidative stress and signalling cascade. Sci. Total Environ.,  2019, 671, 466-473.
 [http://dx.doi.org/10.1016/j.scitotenv.2019.03.381] [PMID:  31331442]

[288]
Dey, R.; Nandi, S.; Samadder, A. “Pelargonidin mediated selective activation of p53 and parp proteins in preventing food additive induced genotoxicity: an in vivo coupled in silico molecular docking study”. Eur. J. Pharm. Sci.,  2021, 156, 105586.
 [http://dx.doi.org/10.1016/j.ejps.2020.105586] [PMID:  33039567]

[289]
Samadder, A.; Tarafdar, D.; Abraham, S.; Ghosh, K.; Khuda-Bukhsh, A. Nano-pelargonidin protects hyperglycemic-induced L6 cells against mitochondrial dysfunction. Planta Med.,  2017, 83(5), 468-475.
 [http://dx.doi.org/10.1055/s-0043-100017] [PMID:  28073120]

[290]
Samadder, A.; Abraham, S.K.; Khuda-Bukhsh, A.R. Nanopharmaceutical approach using pelargonidin towards enhancement of efficacy for prevention of alloxan-induced DNA damage in L6 cells via activation of PARP and p53. Environ. Toxicol. Pharmacol.,  2016, 43, 27-37.
 [http://dx.doi.org/10.1016/j.etap.2016.02.010] [PMID:  26943895]

[291]
Lee, I.C.; Bae, J.S. Pelargonidin protects against renal injury in a mouse model of sepsis. J. Med. Food,  2019, 22(1), 57-61.
 [http://dx.doi.org/10.1089/jmf.2018.4230] [PMID:  30160593]

[292]
Smeriglio, A.; Barreca, D.; Bellocco, E.; Trombetta, D. Chemistry, pharmacology and health benefits of anthocyanins. Phytother. Res.,  2016, 30(8), 1265-1286.
 [http://dx.doi.org/10.1002/ptr.5642] [PMID:  27221033]

[293]
Francomano, F. Caruso, A.; Barbarossa, A.; Fazio, A.; La Torre, C.; Ceramella, J.; Mallamaci, R.; Saturnino, C.; Iacopetta, D.; Sinicropi, M.S. β-Caryophyllene: A sesquiterpene with countless biological properties. Appl. Sci. (Basel),  2019, 9(24), 5420.
 [http://dx.doi.org/10.3390/app9245420]

[294]
Hashiesh, H.M.; Meeran, M.F.N.; Sharma, C.; Sadek, B.; Kaabi, J.A.; Ojha, S.K. Therapeutic potential of β-caryophyllene: A dietary cannabinoid in diabetes and associated complications. Nutrients,  2020, 12(10), 2963.
 [http://dx.doi.org/10.3390/nu12102963] [PMID:  32998300]

[295]
Abbas, M.A. Taha, M.O.; Zihlif, M.A.; Disi, A.M. β-Caryophyllene causes regression of endometrial implants in a rat model of endometriosis without affecting fertility. Eur. J. Pharmacol.,  2013, 702(1-3), 12-19.
 [http://dx.doi.org/10.1016/j.ejphar.2013.01.011] [PMID:  23353590]

[296]
Horváth, B. Mukhopadhyay, P.; Kechrid, M.; Patel, V.; Tanchian, G.; Wink, D.A.; Gertsch, J.; Pacher, P. β-Caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependent manner. Free Radic. Biol. Med.,  2012, 52(8), 1325-1333.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2012.01.014] [PMID:  22326488]

[297]
Li, H. Wang, D.; Chen, Y.; Yang, M. β-Caryophyllene inhibits high glucose-induced oxidative stress, inflammation and extracellular matrix accumulation in mesangial cells. Int. Immunopharmacol.,  2020, 84, 106556.
 [http://dx.doi.org/10.1016/j.intimp.2020.106556] [PMID:  32416450]

[298]
Rajab, B.S.; Albukhari, T.A.; Khan, A.A.; Refaat, B.; Almehmadi, S.J.; Nasreldin, N.; Elshopakey, G.E.; El-Boshy, M. Antioxidative and anti-inflammatory protective effects of β-caryophyllene against amikacin-induced nephrotoxicity in rat by regulating the Nrf2/AMPK/AKT and NF-κB/TGF-β/KIM-1 molecular pathways. Oxid. Med. Cell. Longev.,  2022, 2022, 1-12.
 [http://dx.doi.org/10.1155/2022/4212331] [PMID:  36062191]

[299]
Lo, J.Y.; Kamarudin, M.N.A.; Hamdi, O.A.A.; Awang, K.; Kadir, H.A. Curcumenol isolated from Curcuma zedoaria suppresses Akt-mediated NF-κB activation and p38 MAPK signaling pathway in LPS-stimulated BV-2 microglial cells. Food Funct.,  2015, 6(11), 3550-3559.
 [http://dx.doi.org/10.1039/C5FO00607D] [PMID:  26301513]

[300]
Yoshioka, T.; Fujii, E.; Endo, M.; Wada, K.; Tokunaga, Y.; Shiba, N.; Hohsho, H.; Shibuya, H.; Muraki, T. Antiinflammatory potency of dehydrocurdione, a zedoary-derived sesquiterpene. Inflamm. Res.,  1998, 47(12), 476-481.
 [http://dx.doi.org/10.1007/s000110050361] [PMID:  9892041]

[301]
Ohnishi, M.; Urasaki, T.; Egusa, K.; Kunobu, C.; Harada, T.; Shinkado, R.; Nishi, H.; Maehara, S.; Kitamura, C.; Hata, T.; Ohashi, K.; Shibuya, H.; Inoue, A. Curcuma sp.-derived dehydrocurdione induces heme oxygenase-1 through a Michael reaction between its α, β-unsaturated carbonyl and Keap1. Phytother. Res.,  2018, 32(5), 892-897.
 [http://dx.doi.org/10.1002/ptr.6028] [PMID:  29356228]

[302]
Cui, H.; Zhang, B.; Li, G.; Li, L.; Chen, H.; Qi, J.; Liu, W.; Chen, J.; Wang, P.; Lei, H. Identification of a quality marker of vinegar-Processed Curcuma zedoaria on oxidative liver injury. Molecules,  2019, 24(11), 2073.
 [http://dx.doi.org/10.3390/molecules24112073] [PMID:  31151312]

[303]
Wang, G.G.; Lu, X.H.; Li, W.; Zhao, X.; Zhang, C. Protective effects of luteolin on diabetic nephropathy in STZ-induced diabetic rats. Evid.-based Complement. Altern. Med.,  2011, 2011, 323-171.

[304]
Yu, Q.; Zhang, M.; Qian, L.; Wen, D.; Wu, G. Luteolin attenuates high glucose-induced podocyte injury via suppressing NLRP3 inflammasome pathway. Life Sci.,  2019, 225, 1-7.
 [http://dx.doi.org/10.1016/j.lfs.2019.03.073] [PMID:  30935950]

[305]
Iskender, H.; Dokumacioglu, E.; Sen, T.M.; Ince, I.; Kanbay, Y.; Saral, S. The effect of hesperidin and quercetin on oxidative stress, NF-κB and SIRT1 levels in a STZ-induced experimental diabetes model. Biomed. Pharmacother.,  2017, 90, 500-508.
 [http://dx.doi.org/10.1016/j.biopha.2017.03.102] [PMID:  28395272]

[306]
Elbe, H.; Vardi, N.; Esrefoglu, M.; Ates, B.; Yologlu, S.; Taskapan, C. Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats. Hum. Exp. Toxicol.,  2015, 34(1), 100-113.
 [http://dx.doi.org/10.1177/0960327114531995] [PMID:  24812155]

[307]
Wang, C.; Pan, Y.; Zhang, Q.Y.; Wang, F.M.; Kong, L.D. Quercetin and allopurinol ameliorate kidney injury in STZ-treated rats with regulation of renal NLRP3 inflammasome activation and lipid accumulation. PLoS One,  2012, 7(6), e38285.
 [http://dx.doi.org/10.1371/journal.pone.0038285] [PMID:  22701621]

[308]
Hu, Q.H.; Wang, C.; Li, J.M.; Zhang, D.M.; Kong, L.D. Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: renal organic ion transporter involvement. Am. J. Physiol. Renal Physiol.,  2009, 297(4), F1080-F1091.
 [http://dx.doi.org/10.1152/ajprenal.90767.2008] [PMID:  19605544]

[309]
Kandasamy, N.; Ashokkumar, N. Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats. Toxicol. Appl. Pharmacol.,  2014, 279(2), 173-185.
 [http://dx.doi.org/10.1016/j.taap.2014.05.014] [PMID:  24923654]

[310]
Kandasamy, N.; Ashokkumar, N. Renoprotective effect of myricetin restrains dyslipidemia and renal mesangial cell proliferation by the suppression of sterol regulatory element binding proteins in an experimental model of diabetic nephropathy. Eur. J. Pharmacol.,  2014, 743, 53-62.
 [http://dx.doi.org/10.1016/j.ejphar.2014.09.014] [PMID:  25240712]

[311]
Luo, W.; Chen, X.; Ye, L.; Chen, X.; Jia, W.; Zhao, Y.; Samorodov, A.V.; Zhang, Y.; Hu, X.; Zhuang, F.; Qian, J.; Zheng, C.; Liang, G.; Wang, Y. Kaempferol attenuates streptozotocin-induced diabetic nephropathy by downregulating TRAF6 expression: The role of TRAF6 in diabetic nephropathy. J. Ethnopharmacol.,  2021, 268, 113553.
 [http://dx.doi.org/10.1016/j.jep.2020.113553] [PMID:  33152432]

[312]
Ozcan, F.; Ozmen, A.; Akkaya, B.; Aliciguzel, Y.; Aslan, M. Beneficial effect of myricetin on renal functions in streptozotocin-induced diabetes. Clin. Exp. Med.,  2012, 12(4), 265-272.
 [http://dx.doi.org/10.1007/s10238-011-0167-0] [PMID:  22083509]

[313]
Yang, L.; Liao, M. Influence of myrcene on inflammation, matrix accumulation in the kidney tissues of streptozotocin-induced diabetic rat. Saudi J. Biol. Sci.,  2021, 28(10), 5555-5560.
 [http://dx.doi.org/10.1016/j.sjbs.2020.11.090] [PMID:  34588865]

[314]
Zhongliu, Y. Cancer Review; Yu, R., Ed.; Shanghai Science/Technology Publisher, Peop. Rep: China, 1994. 

[315]
Senthil Kumar, K.J.; Gokila Vani, M.; Wang, C.S.; Chen, C.C.; Chen, Y.C.; Lu, L.P.; Huang, C.H.; Lai, C.S.; Wang, S.Y. Geranium and lemon essential oils and their active compounds downregulate angiotensin-converting enzyme 2 (ACE2), a SARS-CoV-2 spike receptor-binding domain, in epithelial cells. Plants,  2020, 9(6), 770.
 [http://dx.doi.org/10.3390/plants9060770] [PMID:  32575476]

[316]
Kim, H.R.; Kim, W.K.; Ha, A.W. Effects of phytochemicals on blood pressure and neuroprotection mediated via brain renin-angiotensin system. Nutrients,  2019, 11(11), 2761.
 [http://dx.doi.org/10.3390/nu11112761] [PMID:  31739443]

[317]
Jones, H.S.; Gordon, A.; Magwenzi, S.G.; Naseem, K.; Atkin, S.L.; Courts, F.L. The dietary flavonol quercetin ameliorates angiotensin II-induced redox signaling imbalance in a human umbilical vein endothelial cell model of endothelial dysfunction via ablation of p47 phox expression. Mol. Nutr. Food Res.,  2016, 60(4), 787-797.
 [http://dx.doi.org/10.1002/mnfr.201500751] [PMID:  26778209]

[318]
Luo, J.; Zhang, C.; Liu, Q.; Ou, S.; Zhang, L.; Peng, X. Combinative effect of sardine peptides and quercetin alleviates hypertension through inhibition of angiotensin I converting enzyme activity and inflammation. Food Res. Int.,  2017, 100(Pt 1), 579-585.
 [http://dx.doi.org/10.1016/j.foodres.2017.07.019] [PMID:  28873724]

[319]
Guo, X.; Chen, M.; Zeng, H.; Liu, P.; Zhu, X.; Zhou, F.; Liu, J.; Zhang, J.; Dong, Z.; Tang, Y.; Gao, C.; Yao, P. Quercetin attenuates ethanol-induced iron uptake and myocardial injury by regulating the angiotensin II-L-type calcium channel. Mol. Nutr. Food Res.,  2018, 62(5), 1700772.
 [http://dx.doi.org/10.1002/mnfr.201700772] [PMID:  29266790]

[320]
Suchal, K.; Malik, S.; Khan, S.; Malhotra, R.; Goyal, S.; Bhatia, J.; Ojha, S.; Arya, D. Molecular pathways involved in the amelioration of myocardial injury in diabetic rats by kaempferol. Int. J. Mol. Sci.,  2017, 18(5), 1001.
 [http://dx.doi.org/10.3390/ijms18051001] [PMID:  28505121]
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DOI https://dx.doi.org/10.2174/0929867330666230519112312	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

To Explore the Putative Molecular Targets of Diabetic Nephropathy and their Inhibition Utilizing Potential Phytocompounds

Abstract

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the Treatment of Chronic Inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

Current Medicinal Chemistry

To Explore the Putative Molecular Targets of Diabetic Nephropathy and their Inhibition Utilizing Potential Phytocompounds

Abstract

Call for Papers in Thematic Issues

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the Treatment of Chronic Inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

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