Tannins and vascular complications of Diabetes: An update.

BACKGROUND Diabetes mellitus is a chronic metabolic disorder associated with persistent increased level of glucose in the blood. According to a report by World Health Organisation (WHO), prevalence of diabetes among adults over 18 years of age had reached to 8.5% in year 2014 which was 4.7% in 1980s. The Prolong increased level of glucose in blood leads to development of microvascular (blindness, nephropathy and neuropathy) and macrovascular (cardiovascular and stroke) degenerative complications because of uncontrolled level of glucose in blood. This also leads to the progression of oxidative stress and affecting metabolic, genetic and haemodynamic system by activation of polyol pathway, protein kinase C pathway, hexosamine pathway and increases advanced glycation end products (AGEs) formation. Diabetes mellitus and its associated complications are one of the major leading causes of mortality worldwide. Various natural products like alkaloids, glycosides, flavonoids, terpenoids and polyphenols are reported for their activity in management of diabetes and its associated diabetic complications. Tannins are systematically studied by many researchers in past few decades for their effect in diabetes and its complications. AIM The present review was designed to compile the data of tannins and their beneficial effects in the management of diabetic complications. METHOD Literature search was performed using various dataset like pubmed, EBSCO, proQuest Scopus and selected websites including the National Institutes of Health (NIH) and the World Health Organization (WHO). RESULTS Globally, more than 400 natural products have been investigated in diabetes and its complications. Tannins are the polyphenolic compounds present in many medicinal plants and various dietary sources like fruits, nuts, grains, spices and beverages. Various reports have shown that compounds like gallic acid, ellagic acid, catechin, epicatechin and procynidins from medicinal plants play major role in controlling progression of diabetes and its related complications by acting on molecular pathways and key targets involved in progression. Many chemists used above mentioned phyto-constituents as a pharmacophore for the developing new chemical entities having higher therapeutic benefits in management of diabetic complications. CONCLUSION This review focuses on the role of various tannins in prevention and management of diabetic complications like diabetic nephropathy, diabetic neuropathy, diabetic retinopathy and diabetic cardiomyopathy. It will help researchers to find some leads for the development of new cost effective therapy using dietary source for the management of diabetic complications.

[1]  Yong Li,et al.  Proanthocyanidins protect against early diabetic peripheral neuropathy by modulating endoplasmic reticulum stress. , 2014, The Journal of nutritional biochemistry.

[2]  Pengfei Hu,et al.  Regulation of autophagy by tea polyphenols in diabetic cardiomyopathy , 2018, Journal of Zhejiang University-SCIENCE B.

[3]  P. Srinivasan,et al.  Green tea attenuates diabetes induced Maillard-type fluorescence and collagen cross-linking in the heart of streptozotocin diabetic rats. , 2007, Pharmacological research.

[4]  Yaeni Kim,et al.  New therapeutic agents in diabetic nephropathy , 2017, The Korean journal of internal medicine.

[5]  Srijit Das,et al.  Effect of Piper sarmentosum Extract on the Cardiovascular System of Diabetic Sprague-Dawley Rats: Electron Microscopic Study , 2012, Evidence-based complementary and alternative medicine : eCAM.

[6]  Jianan Huang,et al.  Inhibiting effects of epigallocatechin gallate (EGCG) on the formation of age pigment in vitro and in vivo , 2011 .

[7]  Chun-Yin Huang,et al.  Anticoagulatory, antiinflammatory, and antioxidative effects of protocatechuic acid in diabetic mice. , 2009, Journal of agricultural and food chemistry.

[8]  A. Aura,et al.  Tannins: current knowledge of food sources, intake, bioavailability and biological effects. , 2009, Molecular nutrition & food research.

[9]  T. Slaga,et al.  Safety Assessment of Vitis vinifera (Grape)-Derived Ingredients as Used in Cosmetics , 2014, International journal of toxicology.

[10]  M. Mishra,et al.  Transcription factor Nrf2-mediated antioxidant defense system in the development of diabetic retinopathy. , 2013, Investigative ophthalmology & visual science.

[11]  M. Surekha,et al.  Effect of cinnamon and its procyanidin-B2 enriched fraction on diabetic nephropathy in rats. , 2014, Chemico-biological interactions.

[12]  P. Teissèdre,et al.  New insight into the unresolved HPLC broad peak of Cabernet Sauvignon grape seed polymeric tannins by combining CPC and Q-ToF approaches. , 2018, Food chemistry.

[13]  M. Dianat,et al.  Combination of Grape Seed Extract and Exercise Training Improves Left Ventricular Dysfunction in STZ-Induced Diabetic Rats , 2015 .

[14]  M. Abukhalil,et al.  Epigallocatechin-3-gallate protects against diabetic cardiomyopathy through modulating the cardiometabolic risk factors, oxidative stress, inflammation, cell death and fibrosis in streptozotocin-nicotinamide-induced diabetic rats. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[15]  M. Mota,et al.  Anti-inflammatory actions of tannins isolated from the bark of Anacardium occidentale L. , 1985, Journal of ethnopharmacology.

[16]  N. K. Rao,et al.  Antidiabetic and renoprotective effects of the chloroform extract of Terminalia chebula Retz. seeds in streptozotocin-induced diabetic rats , 2006, BMC complementary and alternative medicine.

[17]  A. Sayed,et al.  Thymoquinone and proanthocyanidin attenuation of diabetic nephropathy in rats. , 2010, European review for medical and pharmacological sciences.

[18]  J. M. Petrash,et al.  Design of an amide N-glycoside derivative of β-glucogallin: a stable, potent, and specific inhibitor of aldose reductase. , 2014, Journal of medicinal chemistry.

[19]  J. Björkegren,et al.  Lipoprotein Secretion and Triglyceride Stores in the Heart* , 2001, The Journal of Biological Chemistry.

[20]  Richard J. Johnson,et al.  How does angiotensin II cause renal injury? , 2004, Hypertension.

[21]  H. Founds,et al.  Therapeutic potential of breakers of advanced glycation end product-protein crosslinks. , 2003, Archives of biochemistry and biophysics.

[22]  Yanyan Song,et al.  Epigallocatechin gallate upregulates NRF2 to prevent diabetic nephropathy via disabling KEAP1 , 2017, Free radical biology & medicine.

[23]  Y. Cha,et al.  Neuroprotective effects of Vitis vinifera extract on prediabetic mice induced by a high-fat diet , 2013, The Korean journal of internal medicine.

[24]  A. Panthong,et al.  Acute and chronic oral toxicity of standardized water extract from the fruit of Phyllanthus emblica Linn. , 2010 .

[25]  Jin Sook Kim,et al.  Epicatechin breaks preformed glycated serum albumin and reverses the retinal accumulation of advanced glycation end products. , 2015, European journal of pharmacology.

[26]  Jin Sook Kim Seeds of Cornus officinalis and Diabetic Cataracts , 2014 .

[27]  A. Lim,et al.  Diabetic nephropathy – complications and treatment , 2014, International journal of nephrology and renovascular disease.

[28]  V. Tiwari,et al.  Diabetic nephropathy: New insights into established therapeutic paradigms and novel molecular targets. , 2017, Diabetes research and clinical practice.

[29]  G. Shao,et al.  Tannins from pomegranate seeds ameliorate renal injury in streptozotocin-induced diabetic rat through the activation of microRNA-495 via regulating SMAD 7 , 2017 .

[30]  Y. Kulkarni,et al.  Bauhinia variegata (Caesalpiniaceae) leaf extract: An effective treatment option in type I and type II diabetes. , 2016, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[31]  M. Abdulla,et al.  Antioxidant and pro-oxidant effects of oil palm (Elaeis guineensis) leaves extract in experimental diabetic nephropathy: a duration-dependent outcome , 2013, BMC Complementary and Alternative Medicine.

[32]  K. Sabitha,et al.  GREEN TEA EXTRACT IMPEDES DYSLIPIDAEMIA AND DEVELOPMENT OF CARDIAC DYSFUNCTION IN STREPTOZOTOCIN‐DIABETIC RATS , 2006, Clinical and experimental pharmacology & physiology.

[33]  H. Ou,et al.  Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways in streptozotocin-induced diabetic rats. , 2013, International journal of cardiology.

[34]  M. Abdelsaid,et al.  Early Intervention of Tyrosine Nitration Prevents Vaso-Obliteration and Neovascularization in Ischemic Retinopathy , 2009, Journal of Pharmacology and Experimental Therapeutics.

[35]  K. Itoh,et al.  An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. , 1997, Biochemical and biophysical research communications.

[36]  R. Goyal,et al.  Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats , 2011, Pharmacognosy research.

[37]  T. Inoue,et al.  Toxicological studies on procyanidin B-2 for external application as a hair growing agent. , 1999, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[38]  J. M. Petrash,et al.  Aldose reductase inhibition alleviates hyperglycemic effects on human retinal pigment epithelial cells. , 2015, Chemico-biological interactions.

[39]  A. Kuhad,et al.  Amelioration of functional, biochemical and molecular deficits by epigallocatechin gallate in experimental model of alcoholic neuropathy , 2011, European journal of pain.

[40]  M. Nangaku,et al.  In a type 2 diabetic nephropathy rat model, the improvement of obesity by a low calorie diet reduces oxidative/carbonyl stress and prevents diabetic nephropathy. , 2005, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[41]  R. Isbrucker,et al.  Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: teratogenicity and reproductive toxicity studies in rats. , 2006, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[42]  Paul J Thornalley Glycation in diabetic neuropathy: characteristics, consequences, causes, and therapeutic options. , 2002, International review of neurobiology.

[43]  Y. Kulkarni,et al.  Hyperglycemia to nephropathy via transforming growth factor beta. , 2014, Current diabetes reviews.

[44]  Y. Kulkarni,et al.  Attenuation of renal damage in type I diabetic rats by umbelliferone — a coumarin derivative , 2017, Pharmacological reports : PR.

[45]  D. Tracey,et al.  Immune and inflammatory mechanisms in neuropathic pain , 2006, Brain Research Reviews.

[46]  K. Trudeau,et al.  High glucose disrupts mitochondrial morphology in retinal endothelial cells: implications for diabetic retinopathy. , 2010, The American journal of pathology.

[47]  Cristóbal N. Aguilar,et al.  Pentagalloylglucose (PGG): A valuable phenolic compound with functional properties , 2017 .

[48]  F. Milagro,et al.  Healthy properties of proanthocyanidins , 2010, BioFactors.

[49]  D. Cherkin,et al.  Unanticipated benefits of CAM therapies for back pain: an exploration of patient experiences. , 2010, Journal of alternative and complementary medicine.

[50]  S. Tian,et al.  Propyl Gallate Plays a Nephroprotective Role in Early Stage of Diabetic Nephropathy Associated with Suppression of Glomerular Endothelial Cell Proliferation and Angiogenesis , 2012, Experimental diabetes research.

[51]  M. A. Mahgoub,et al.  Diabetes mellitus and cardiac function , 1998, Molecular and Cellular Biochemistry.

[52]  K. Toyoda,et al.  Subchronic toxicity study of gallic acid by oral administration in F344 rats. , 2001, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[53]  N. Lopes,et al.  Polyphenol-enriched cocoa protects the diabetic retina from glial reaction through the sirtuin pathway. , 2015, The Journal of nutritional biochemistry.

[54]  T. Mukherjee,et al.  Physico-Chemical Studies on the Evaluation of the Antioxidant Activity of Herbal Extracts and Active Principles of Some Indian Medicinal Plants , 2007, Journal of clinical biochemistry and nutrition.

[55]  Bao‐ying Li,et al.  Back‐regulation of six oxidative stress proteins with grape seed proanthocyanidin extracts in rat diabetic nephropathy , 2008, Journal of cellular biochemistry.

[56]  Ludmil Benov,et al.  Possible role of antioxidative capacity of (-)-epigallocatechin-3-gallate treatment in morphological and neurobehavioral recovery after sciatic nerve crush injury. , 2017, Journal of neurosurgery. Spine.

[57]  K. Upadhyaya,et al.  Tannins are Astringent , 2012 .

[58]  C. Rivard,et al.  Abnormal Angiogenesis in Diabetic Nephropathy , 2009, Diabetes.

[59]  R. Qin,et al.  Quantitative proteomics study of protective effects of grape seed procyanidin B2 on diabetic cardiomyopathy in db/db mice , 2014, Bioscience, biotechnology, and biochemistry.

[60]  R. Goyal,et al.  Prevention of diabetes-induced myocardial dysfunction in rats using the juice of the Emblica officinalis fruit. , 2011, Experimental and clinical cardiology.

[61]  M. Roller,et al.  Food and Chemical Toxicology , 2013 .

[62]  M. Moridani,et al.  Renoprotective effects of (+)-catechin in streptozotocin-induced diabetic rat model. , 2012, Nutrition research.

[63]  T. Mitsuhashi,et al.  Importance of hypercoagulability over hyperglycemia for vascular complication in type 2 diabetes. , 2000, Diabetes research and clinical practice.

[64]  I. Tavares,et al.  Nociceptive spinal cord neurons of laminae I–III exhibit oxidative stress damage during diabetic neuropathy which is prevented by early antioxidant treatment with epigallocatechin-gallate (EGCG) , 2015, Brain Research Bulletin.

[65]  Hongli Li,et al.  Potential role of cyanidin 3-glucoside (C3G) in diabetic cardiomyopathy in diabetic rats: An in vivo approach , 2016, Saudi journal of biological sciences.

[66]  J. Mak Potential role of green tea catechins in various disease therapies: Progress and promise , 2012, Clinical and experimental pharmacology & physiology.

[67]  Doaa S. Ibrahim,et al.  Effect of strawberry (Fragaria × ananassa) leaf extract on diabetic nephropathy in rats , 2015, International journal of experimental pathology.

[68]  A. Doss,et al.  Antibacterial Activity of Tannins from the Leaves of Solanum trilobatum Linn. , 2009 .

[69]  H. Jeong,et al.  Effects of Epigallocatechin-3-Gallate on the Expression of TGF-β1, PKC α/βII, and NF-κB in High-Glucose-Stimulated Glomerular Epithelial Cells , 2011, Chonnam medical journal.

[70]  A. Barden,et al.  Advanced Glycation End Products: A Review , 2013 .

[71]  Iyuki Namekata,et al.  Ellagic acid and gingerol, activators of the sarco-endoplasmic reticulum Ca²⁺-ATPase, ameliorate diabetes mellitus-induced diastolic dysfunction in isolated murine ventricular myocardia. , 2013, European journal of pharmacology.

[72]  M. Bähr,et al.  Bax antisense oligonucleotides reduce axotomy-induced retinal ganglion cell death in vivo by reduction of Bax protein expression , 1999, Cell Death and Differentiation.

[73]  P. Suryanarayana,et al.  Inhibition of protein glycation by procyanidin‐B2 enriched fraction of cinnamon: Delay of diabetic cataract in rats , 2013, IUBMB life.

[74]  R. Kopito,et al.  Aggresomes: A Cellular Response to Misfolded Proteins , 1998, The Journal of cell biology.

[75]  D. Granato,et al.  In vitro antioxidant and antihypertensive compounds from camu-camu (Myrciaria dubia McVaugh, Myrtaceae) seed coat: A multivariate structure-activity study. , 2018, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[76]  Richard A. Anderson,et al.  Green tea polyphenols improve cardiac muscle mRNA and protein levels of signal pathways related to insulin and lipid metabolism and inflammation in insulin-resistant rats. , 2010, Molecular nutrition & food research.

[77]  Liping Xu,et al.  Mechanism of Tang Luo Ning effect on attenuating of oxidative stress in sciatic nerve of STZ-induced diabetic rats. , 2015, Journal of ethnopharmacology.

[78]  G. Fu,et al.  Epigallocatechin-3 Gallate, a Green Tea Catechin, Attenuated the Downregulation of the Cardiac Gap Junction Induced by High Glucose in Neonatal Rat Cardiomyocytes , 2010, Cellular Physiology and Biochemistry.

[79]  X. Yin,et al.  Effective compounds group of Mongolian prescriptions BAIMAI-SAN protect against peripheral neuropathy in lower limbs of rats through neuro protective effect. , 2011, Journal of ethnopharmacology.

[80]  P. Kumar,et al.  Ellagic acid inhibits non-enzymatic glycation and prevents proteinuria in diabetic rats. , 2016, Food & function.

[81]  Yeong Shik Kim,et al.  Epigalloccatechin-3-gallate Inhibits Ocular Neovascularization and Vascular Permeability in Human Retinal Pigment Epithelial and Human Retinal Microvascular Endothelial Cells via Suppression of MMP-9 and VEGF Activation , 2014, Molecules.

[82]  B. Bhandary,et al.  ACUTE AND SUBACUTE TOXICITY STUDY OF THE ETHANOL EXTRACTS OF PUNICA GRANATUM (LINN). WHOLE FRUIT AND SEEDS AND SYNTHETIC ELLAGIC ACID IN SWISS ALBINO MICE , 2013 .

[83]  B. Turchetti,et al.  Antimicrobial and antiviral activity of hydrolysable tannins. , 2008, Mini reviews in medicinal chemistry.

[84]  M. Kikuchi,et al.  Safety evaluation of proanthocyanidin-rich extract from grape seeds. , 2002, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[85]  S. Chatterjee,et al.  Acute and sub-chronic oral toxicity study of black tea in rodents , 2015, Indian journal of pharmacology.

[86]  Wen-Bin Wu,et al.  Effects of (-)-epigallocatechin gallate on RPE cell migration and adhesion , 2010, Molecular vision.

[87]  A. Verkhratsky,et al.  Diabetes-induced alterations in calcium homeostasis in sensory neurones of streptozotocin-diabetic rats are restricted to lumbar ganglia and are prevented by neurotrophin-3 , 2002, Diabetologia.

[88]  N. Malleshi,et al.  Inhibition of aldose reductase from cataracted eye lenses by finger millet (Eleusine coracana) polyphenols. , 2008, Bioorganic & medicinal chemistry.

[89]  P. Muthenna,et al.  Ellagic acid, a new antiglycating agent: its inhibition of Nϵ-(carboxymethyl)lysine. , 2012, The Biochemical journal.

[90]  H. Vlassara Advanced glycation end-products and atherosclerosis. , 1996, Annals of medicine.

[91]  M. Beck,et al.  28-Day oral (gavage) toxicity studies of green tea catechins prepared for beverages in rats. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[92]  R. Bruzzone,et al.  Connections with connexins: the molecular basis of direct intercellular signaling. , 1996, European journal of biochemistry.

[93]  C. Akileshwari,et al.  Attenuation of diabetic retinopathy in rats by ellagic acid through inhibition of AGE formation , 2017, Journal of Food Science and Technology.

[94]  N. Dhalla,et al.  Pathogenesis of cardiac dysfunction in diabetes mellitus. , 1985, The Canadian journal of cardiology.

[95]  Z. Makita,et al.  Pigment epithelium-derived factor protects cultured retinal pericytes from advanced glycation end product-induced injury through its antioxidative properties. , 2002, Biochemical and biophysical research communications.

[96]  M. Yin,et al.  Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice , 2009, Nutrition & metabolism.

[97]  Daniel Shu Wei Ting MMed,et al.  Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review , 2016 .

[98]  A. Khalatbary,et al.  Therapeutic potential of Juglans regia L. leaf extract against diabetic retinopathy in rat , 2017, Iranian journal of basic medical sciences.

[99]  Ling Lai,et al.  Advanced glycation end products‐induced apoptosis attenuated by PPARδ activation and epigallocatechin gallate through NF‐κB pathway in human embryonic kidney cells and human mesangial cells , 2010, Diabetes/metabolism research and reviews.

[100]  J. Perchellet,et al.  Antitumor-promoting activities of tannic acid, ellagic acid, and several gallic acid derivatives in mouse skin. , 1992, Basic life sciences.

[101]  Li Li Guo,et al.  Epigallocatechin-3-gallate Attenuates Renal Damage by Suppressing Oxidative Stress in Diabetic db/db Mice , 2016, Oxidative medicine and cellular longevity.

[102]  Y. Kulkarni,et al.  NF-κβ: A Potential Target in the Management of Vascular Complications of Diabetes , 2017, Front. Pharmacol..

[103]  M. Brownlee Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[104]  J. M. Petrash,et al.  Bioflavonoid ellagic acid inhibits aldose reductase: Implications for prevention of diabetic complications , 2014 .

[105]  Yao-Jen Liang,et al.  Epigallocatechin-3-gallate combined with alpha lipoic acid attenuates high glucose-induced receptor for advanced glycation end products (RAGE) expression in human embryonic kidney cells. , 2013, Anais da Academia Brasileira de Ciencias.

[106]  P. He,et al.  Procyanidin B2 inhibits high glucose‑induced epithelial‑mesenchymal transition in HK‑2 human renal proximal tubular epithelial cells. , 2015, Molecular medicine reports.

[107]  V. Usuelli,et al.  Novel therapeutic approaches for diabetic nephropathy and retinopathy. , 2015, Pharmacological research.

[108]  V. Vadivel,et al.  Antioxidant and antidiabetic properties of condensed tannins in acetonic extract of selected raw and processed indigenous food ingredients from Kenya. , 2011, Journal of food science.

[109]  M. Sternberg,et al.  Advanced glycation endproducts (AGEs): Pharmacological inhibition in diabetes. , 2006, Pathologie-biologie.

[110]  S. Quideau Chemistry and biology of ellagitannins : an underestimated class of bioactive plant polyphenols , 2009 .

[111]  Yong Li,et al.  Grape seed procyanidin B2 protects podocytes from high glucose-induced mitochondrial dysfunction and apoptosis via the AMPK-SIRT1-PGC-1α axis in vitro. , 2016, Food & function.

[112]  GodwinSelvarajEsther,et al.  Molecular docking studies of Ellagic Acid and Gallic Acid In diabeticNephropathy , 2014 .

[113]  M. Brownlee,et al.  Advanced protein glycosylation in diabetes and aging. , 1995, Annual review of medicine.

[114]  K. Whitney,et al.  Subchronic 3-month oral toxicity study of grape seed and grape skin extracts. , 2002, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[115]  Y. Kulkarni,et al.  Gallic acid attenuates type I diabetic nephropathy in rats. , 2018, Chemico-biological interactions.

[116]  P. Huang,et al.  Reduced severity of oxygen-induced retinopathy in eNOS-deficient mice. , 2001, Investigative ophthalmology & visual science.

[117]  M. Fan,et al.  Cellular apoptosis and cardiac dysfunction in STZ‐induced diabetic rats attenuated by anthocyanins via activation of IGFI‐R/PI3K/Akt survival signaling , 2017, Environmental toxicology.

[118]  S. Shankar,et al.  Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. , 2011, Biochemical pharmacology.

[119]  G. Luo,et al.  Blockade of the Formation of Insoluble Ubiquitinated Protein Aggregates by EGCG3”Me in the Alloxan-Induced Diabetic Kidney , 2013, PloS one.

[120]  Mark D. Huffman,et al.  AHA Statistical Update Heart Disease and Stroke Statistics — 2012 Update A Report From the American Heart Association WRITING GROUP MEMBERS , 2010 .

[121]  Nahid Hasan,et al.  Protective role of green tea on diabetic nephropathy—A review , 2016 .

[122]  U. Smith,et al.  Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. , 2006, The New England journal of medicine.

[123]  A. Gaikwad,et al.  Gallotannin ameliorates the development of streptozotocin‐induced diabetic nephropathy by preventing the activation of PARP , 2009, Phytotherapy research : PTR.

[124]  M. Chaves,et al.  The stem bark extracts of Cenostigma macrophyllum attenuates tactile allodynia in streptozotocin-induced diabetic rats , 2013, Pharmaceutical biology.

[125]  A. Basbaum,et al.  Transmitting Pain and Itch Messages: A Contemporary View of the Spinal Cord Circuits that Generate Gate Control , 2014, Neuron.

[126]  Y. Hung,et al.  Kidney-targeting Smad7 gene transfer inhibits renal TGF-β/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways, and improves diabetic nephropathy in mice , 2012, Diabetologia.

[127]  R. Bucala,et al.  Advanced glycation end products increase retinal vascular endothelial growth factor expression. , 1998, The Journal of clinical investigation.

[128]  K. Block,et al.  Green tea (Camellia sinensis) attenuates nephropathy by downregulating Nox4 NADPH oxidase in diabetic spontaneously hypertensive rats. , 2009, The Journal of nutrition.

[129]  Jie-Ping Zhu,et al.  (−)-Epigallocatechin-3-gallate attenuates myocardial injury induced by ischemia/reperfusion in diabetic rats and in H9c2 cells under hyperglycemic conditions , 2017, International journal of molecular medicine.

[130]  M. Kumari,et al.  Tannins: An Antinutrient with Positive Effect to Manage Diabetes , 2012 .

[131]  J. M. Landete Ellagitannins, ellagic acid and their derived metabolites: A review about source, metabolism, functions and health , 2011 .

[132]  R. Isbrucker,et al.  Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: dermal, acute and short-term toxicity studies. , 2006, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[133]  Y. Lee,et al.  Galloyl glucoses from the seeds of Cornus officinalis with inhibitory activity against protein glycation, aldose reductase, and cataractogenesis ex vivo. , 2011, Biological & pharmaceutical bulletin.

[134]  T. Imai,et al.  Evaluation of toxicity of green tea catechins with 90-day dietary administration to F344 rats. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[135]  B. Özçelik,et al.  Influence of processing conditions on procyanidin profiles and antioxidant capacity of chocolates: Optimization of dark chocolate manufacturing by response surface methodology , 2016 .

[136]  T. Yokozawa,et al.  Attenuation of oxidative stress and inflammation by gravinol in high glucose-exposed renal tubular epithelial cells. , 2010, Toxicology.

[137]  Z. Dong,et al.  Effect of tannic acid on myocardial lesions in diabetic rats and its mechanism , 2011, Proceedings 2011 International Conference on Human Health and Biomedical Engineering.

[138]  Rui-hai Zhou,et al.  Proteomic analysis of kidney and protective effects of grape seed procyanidin B2 in db/db mice indicate MFG-E8 as a key molecule in the development of diabetic nephropathy. , 2013, Biochimica et biophysica acta.

[139]  S. Yagihashi,et al.  Polyol pathway and diabetic nephropathy revisited: Early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase , 2010, Journal of diabetes investigation.

[140]  A. Barber,et al.  Nrf2 as molecular target for polyphenols: A novel therapeutic strategy in diabetic retinopathy , 2016, Critical reviews in clinical laboratory sciences.

[141]  H. Devaraj,et al.  Assessment of the no-observed-adverse-effect level (NOAEL) of gallic acid in mice. , 2001, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[142]  Bao‐ying Li,et al.  Grape Seed Proanthocyanidins Ameliorate Diabetic Nephropathy via Modulation of Levels of AGE, RAGE and CTGF , 2009, Nephron Experimental Nephrology.

[143]  A. Juvekar,et al.  Attenuation of diabetic nephropathy in streptozotocin-induced diabetic rats by Punica granatum Linn. leaves extract , 2016, Journal of traditional and complementary medicine.

[144]  P. Suryanarayana,et al.  The Isolation and Characterization of β-Glucogallin as a Novel Aldose Reductase Inhibitor from Emblica officinalis , 2012, PloS one.

[145]  Yujie Li,et al.  Grape seed proanthocyanidin extracts ameliorate podocyte injury by activating peroxisome proliferator-activated receptor-γ coactivator 1α in low-dose streptozotocin-and high-carbohydrate/high-fat diet-induced diabetic rats. , 2014, Food & function.

[146]  M. Yin,et al.  Anti-glycative and anti-inflammatory effects of caffeic acid and ellagic acid in kidney of diabetic mice. , 2010, Molecular nutrition & food research.

[147]  D. E. Hamassaki,et al.  Green tea is neuroprotective in diabetic retinopathy. , 2013, Investigative ophthalmology & visual science.

[148]  K. Saigo,et al.  Genotoxicity studies on green tea catechin. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[149]  W. Samy,et al.  Amelioration of Diabetes and Painful Diabetic Neuropathy by Punica granatum L. Extract and Its Spray Dried Biopolymeric Dispersions , 2014, Evidence-based complementary and alternative medicine : eCAM.

[150]  H. Ahsan,et al.  Gallic acid ameliorates renal functions by inhibiting the activation of p38 MAPK in experimentally induced type 2 diabetic rats and cultured rat proximal tubular epithelial cells. , 2015, Chemico-biological interactions.

[151]  K. Ahamed,et al.  Protective effect of tannins from Ficus racemosa in hypercholesterolemia and diabetes induced vascular tissue damage in rats. , 2012, Asian Pacific journal of tropical medicine.

[152]  Thanka Johnson,et al.  Impact of EGCG Supplementation on the Progression of Diabetic Nephropathy in Rats: An Insight into Fibrosis and Apoptosis. , 2017, Journal of agricultural and food chemistry.

[153]  Chun-Fa Huang,et al.  A subacute toxicity evaluation of green tea (Camellia sinensis) extract in mice. , 2011, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[154]  A. Marble Diabetic nephropathy. , 1955, The Journal of clinical endocrinology and metabolism.

[155]  Rayaz A. Malik,et al.  Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments , 2010, Diabetes Care.

[156]  A. Nègre-Salvayre,et al.  Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors , 2008, British journal of pharmacology.