Antioxidative Effects of Natural Products on Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes and results in high mortality. It is therefore imperative to develop novel therapeutics for the prevention or inhibition of the progression of DCM. Oxidative stress is a key mechanism by which diabetes induces DCM. Hence, targeting of oxidative stress-related processes in DCM could be a promising therapeutic strategy. To date, a number of studies have shown beneficial effects of several natural products on the attenuation of DCM via an antioxidative mechanism of action. The aim of the present review is to provide a comprehensive and concise overview of the previously reported antioxidant natural products in the inhibition of DCM progression. Clinical trials of the antioxidative natural products in the management of DCM are included. In addition, discussion and perspectives are further provided in the present review.

[1]  E. El-Sayed,et al.  Curcumin Ameliorates Streptozotocin‐Induced Heart Injury in Rats , 2014, Journal of biochemical and molecular toxicology.

[2]  D. Zheng,et al.  Exogenous Hydrogen Sulfide Attenuates Cardiac Fibrosis Through Reactive Oxygen Species Signal Pathways in Experimental Diabetes Mellitus Models , 2015, Cellular Physiology and Biochemistry.

[3]  Kumar Sharma,et al.  Mitochondrial Hormesis and Diabetic Complications , 2015, Diabetes.

[4]  C. Rivera,et al.  Expression of GluK1c underlies the developmental switch in presynaptic kainate receptor function , 2012, Scientific Reports.

[5]  D. Harrison,et al.  Distinct roles of Nox1 and Nox4 in basal and angiotensin II-stimulated superoxide and hydrogen peroxide production. , 2008, Free radical biology & medicine.

[6]  S. Twigg,et al.  Fibrosis in diabetes complications: Pathogenic mechanisms and circulating and urinary markers , 2008, Vascular health and risk management.

[7]  D. Laight,et al.  The effects of garlic extract upon endothelial function, vascular inflammation, oxidative stress and insulin resistance in adults with type 2 diabetes at high cardiovascular risk. A pilot double blind randomized placebo controlled trial. , 2016, Journal of diabetes and its complications.

[8]  L. Cai,et al.  The Magnolia Bioactive Constituent 4-O-Methylhonokiol Protects against High-Fat Diet-Induced Obesity and Systemic Insulin Resistance in Mice , 2014, Oxidative medicine and cellular longevity.

[9]  Donna D. Zhang.  Mechanistic Studies of the Nrf2-Keap1 Signaling Pathway , 2006, Drug metabolism reviews.

[10]  Ashutosh Kumar,et al.  Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes. , 2011, Current neurovascular research.

[11]  Xiaokun Li,et al.  Inhibition of JNK Phosphorylation by a Novel Curcumin Analog Prevents High Glucose–Induced Inflammation and Apoptosis in Cardiomyocytes and the Development of Diabetic Cardiomyopathy , 2014, Diabetes.

[12]  X. He,et al.  Protection against Chromium (VI)‐induced oxidative stress and apoptosis by Nrf2. recruiting Nrf2 into the nucleus and disrupting the nuclear Nrf2/Keap1 association by toxic metal , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[13]  Charlotte Kloft,et al.  Is There a Risk of Bleeding Associated with Standardized Ginkgo bilobaExtract Therapy? A Systematic Review and Meta‐analysis , 2011, Pharmacotherapy.

[14]  C. Jun,et al.  Progress in researches on the pharmaceutical mechanism and clinical application ofGinkgo Biloba extract on various kinds of diseases , 2006, Chinese journal of integrative medicine.

[15]  Kenichi Watanabe,et al.  Tiny molecule, big power: Multi-target approach for curcumin in diabetic cardiomyopathy. , 2017, Nutrition.

[16]  Q. Qian,et al.  Effect of Salvia miltiorrhiza Hydrophilic Extract on Antioxidant Enzymes in Diabetic Patients with Chronic Heart Disease: A Randomized Controlled Trial , 2012, Phytotherapy research : PTR.

[17]  H. Cai.  NAD(P)H oxidase-dependent self-propagation of hydrogen peroxide and vascular disease. , 2005, Circulation research.

[18]  M. Yimam,et al.  Effects of Aloe vera supplementation in subjects with prediabetes/metabolic syndrome. , 2013, Metabolic syndrome and related disorders.

[19]  L. Cai,et al.  Metallothionein plays a prominent role in the prevention of diabetic nephropathy by sulforaphane via up-regulation of Nrf2. , 2015, Free radical biology & medicine.

[20]  Jiliang Wu,et al.  Flos Puerariae Extract Prevents Myocardial Apoptosis via Attenuation Oxidative Stress in Streptozotocin-Induced Diabetic Mice , 2014, PloS one.

[21]  C. Stefanadis,et al.  Distinct association of admission hyperglycemia with one-year adverse outcome in diabetic and non-diabetic patients with acute ST-elevation myocardial infarction. , 2013, Hellenic Journal of Cardiology.

[22]  K. Itoh,et al.  Keap1-dependent Proteasomal Degradation of Transcription Factor Nrf2 Contributes to the Negative Regulation of Antioxidant Response Element-driven Gene Expression* , 2003, Journal of Biological Chemistry.

[23]  P. Shanthi,et al.  Kalpaamruthaa modulates oxidative stress in cardiovascular complication associated with type 2 diabetes mellitus through PKC-β/Akt signaling. , 2013, Canadian journal of physiology and pharmacology.

[24]  J. Sadoshima,et al.  Upregulation of Nox4 by Hypertrophic Stimuli Promotes Apoptosis and Mitochondrial Dysfunction in Cardiac Myocytes , 2010, Circulation research.

[25]  T. Nag,et al.  Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation. , 2016, Chemico-biological interactions.

[26]  Mohd Ali Hashim,et al.  Superoxide Ion: Generation and Chemical Implications. , 2016, Chemical reviews.

[27]  Nishat Fatima,et al.  Study of pharmacodynamic interaction of Phyllanthus emblica extract with clopidogrel and ecosprin in patients with type II diabetes mellitus. , 2014, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[28]  R. Salie,et al.  The cardioprotective effect of an aqueous extract of fermented rooibos (Aspalathus linearis) on cultured cardiomyocytes derived from diabetic rats. , 2014, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[29]  Paul J Thornalley,et al.  Activation of NF-E2–Related Factor-2 Reverses Biochemical Dysfunction of Endothelial Cells Induced by Hyperglycemia Linked to Vascular Disease , 2008, Diabetes.

[30]  Shyam Biswal,et al.  Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. , 2007, Annual review of pharmacology and toxicology.

[31]  E. Ogier-Denis,et al.  NAD(P)H Oxidase Nox-4 Mediates 7-Ketocholesterol-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Aortic Smooth Muscle Cells , 2004, Molecular and Cellular Biology.

[32]  A. Wen,et al.  Aralia taibaiensis Protects Cardiac Myocytes against High Glucose-Induced Oxidative Stress and Apoptosis. , 2015, The American journal of Chinese medicine.

[33]  Zhubo Li,et al.  Dendrobium officinale Kimura et Migo attenuates diabetic cardiomyopathy through inhibiting oxidative stress, inflammation and fibrosis in streptozotocin-induced mice. , 2016, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[34]  Devendra Vaishnav,et al.  Ficus recemosa bark extract attenuates diabetic complications and oxidative stress in STZ-induced diabetic rats , 2016, Pharmaceutical biology.

[35]  N. Sundaresan,et al.  Defective Nrf2-dependent redox signalling contributes to microvascular dysfunction in type 2 diabetes. , 2013, Cardiovascular research.

[36]  P. Viswanathan,et al.  Renoprotective effect of aged garlic extract in streptozotocin-induced diabetic rats , 2013, Indian journal of pharmacology.

[37]  S. Bailey,et al.  Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes. , 2012, American journal of physiology. Cell physiology.

[38]  Yi Tan,et al.  Metallothionein Is Downstream of Nrf2 and Partially Mediates Sulforaphane Prevention of Diabetic Cardiomyopathy , 2016, Diabetes.

[39]  L. Cai,et al.  Sulforaphane Prevents Angiotensin II-Induced Testicular Cell Death via Activation of NRF2 , 2017, Oxidative medicine and cellular longevity.

[40]  U. Hoffmann,et al.  Aged garlic extract improves homocysteine-induced endothelial dysfunction in macro- and microcirculation. , 2006, The Journal of nutrition.

[41]  E. Abel,et al.  Diabetic cardiomyopathy revisited. , 2007, Circulation.

[42]  R. Malik,et al.  Diabetic cardiomyopathy: mechanisms, diagnosis and treatment. , 2004, Clinical science.

[43]  P. Shanthi,et al.  Kalpaamruthaa ameliorates myocardial and aortic damage in cardiovascular complications associated with type 2 diabetes mellitus. , 2013, Canadian journal of physiology and pharmacology.

[44]  M. Hori,et al.  Effect of intracoronary thrombectomy on 30-day mortality in non-diabetic patients with acute hyperglycemia after acute myocardial infarction. , 2009, Journal of cardiology.

[45]  P. Umbarkar,et al.  Mitochondrial Peroxiredoxin-3 protects against hyperglycemia induced myocardial damage in Diabetic cardiomyopathy. , 2016, Free radical biology & medicine.

[46]  L. Cai,et al.  Diabetic cardiomyopathy and its mechanisms: Role of oxidative stress and damage , 2014, Journal of diabetes investigation.

[47]  Yiheng Wang,et al.  Betanin reduces the accumulation and cross-links of collagen in high-fructose-fed rat heart through inhibiting non-enzymatic glycation. , 2015, Chemico-biological interactions.

[48]  J. Drzewoski,et al.  Can the onset of heart failure be delayed by treating diabetic cardiomyopathy? , 2017, Diabetology & Metabolic Syndrome.

[49]  P. Tsao,et al.  Diabetic Cardiovascular Disease Induced by Oxidative Stress , 2015, International journal of molecular sciences.

[50]  M. Rafraf,et al.  Chamomile tea improves glycemic indices and antioxidants status in patients with type 2 diabetes mellitus. , 2016, Nutrition.

[51]  P. Shanthi,et al.  Protective role of Kalpaamruthaa in type II diabetes mellitus-induced cardiovascular disease through the modulation of protease-activated receptor-1 , 2015, Pharmacognosy magazine.

[52]  L. Cai,et al.  Inhibition of JNK by compound C66 prevents pathological changes of the aorta in STZ-induced diabetes , 2014, Journal of cellular and molecular medicine.

[53]  Chao Liu,et al.  Curcumin Alleviates Diabetic Cardiomyopathy in Experimental Diabetic Rats , 2012, PloS one.

[54]  A. Schmidt,et al.  Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. , 2001, American journal of physiology. Endocrinology and metabolism.

[55]  A. Dashti,et al.  Effect of Black Tea Consumption on Intracellular Cytokines, Regulatory T Cells and Metabolic Biomarkers in Type 2 Diabetes Patients , 2016, Phytotherapy research : PTR.

[56]  Q. Ma,et al.  NRF2 Cysteine Residues Are Critical for Oxidant/Electrophile-Sensing, Kelch-Like ECH-Associated Protein-1-Dependent Ubiquitination-Proteasomal Degradation, and Transcription Activation , 2009, Molecular Pharmacology.

[57]  C. Gardana,et al.  Quantitative characterization of flavonoid compounds in Rooibos tea (Aspalathus linearis) by LC-UV/DAD. , 2002, Journal of agricultural and food chemistry.

[58]  R. Gottlieb,et al.  Myocardial stress and autophagy: mechanisms and potential therapies , 2017, Nature Reviews Cardiology.

[59]  V. Fischer,et al.  Capillary Basal Laminar Thickness in Diabetic Human Myocardium , 1979, Diabetes.

[60]  Li Chen,et al.  [Icariin reduces mitochondrial oxidative stress injury in diabetic rat hearts]. , 2011, Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica.

[61]  K. Channon,et al.  Preoperative Atorvastatin Treatment in CABG Patients Rapidly Improves Vein Graft Redox State by Inhibition of Rac1 and NADPH-Oxidase Activity , 2010, Circulation.

[62]  S. Srivastava,et al.  Protective effects of magnesium lithospermate B against diabetic atherosclerosis via Nrf2-ARE-NQO1 transcriptional pathway. , 2010, Atherosclerosis.

[63]  L. Cai,et al.  Magnolia Bioactive Constituent 4-O-Methylhonokiol Prevents the Impairment of Cardiac Insulin Signaling and the Cardiac Pathogenesis in High-Fat Diet-Induced Obese Mice , 2015, International journal of biological sciences.

[64]  A. Wen,et al.  Antihyperglycemic, hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis in experimental type 2 diabetic rats. , 2014, Journal of ethnopharmacology.

[65]  H. Huttunen,et al.  Coregulation of Neurite Outgrowth and Cell Survival by Amphoterin and S100 Proteins through Receptor for Advanced Glycation End Products (RAGE) Activation* , 2000, The Journal of Biological Chemistry.

[66]  J. Shaw,et al.  Global estimates of the prevalence of diabetes for 2010 and 2030. , 2010, Diabetes research and clinical practice.

[67]  M. Kwak,et al.  Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[68]  M. Nagata,et al.  Curcumin prevents diabetic cardiomyopathy in streptozotocin-induced diabetic rats: possible involvement of PKC-MAPK signaling pathway. , 2012, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[69]  G. Gupta,et al.  Management of diabetic complications: a chemical constituents based approach. , 2013, Journal of ethnopharmacology.

[70]  F. Villarreal,et al.  The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy. , 2006, Journal of the American College of Cardiology.

[71]  Chieh-Hsi Wu,et al.  Inhibitory Effect of Magnolia Officinalis and Lovastatin on Aortic Oxidative Stress and Apoptosis in Hyperlipidemic Rabbits , 2006, Journal of cardiovascular pharmacology.

[72]  N. Mellen,et al.  Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway. , 2014, Journal of molecular and cellular cardiology.

[73]  Mark Hannink,et al.  Distinct Cysteine Residues in Keap1 Are Required for Keap1-Dependent Ubiquitination of Nrf2 and for Stabilization of Nrf2 by Chemopreventive Agents and Oxidative Stress , 2003, Molecular and Cellular Biology.

[74]  Xiuxia Liu,et al.  Sodium butyrate activates NRF2 to ameliorate diabetic nephropathy possibly via inhibition of HDAC. , 2017, The Journal of endocrinology.

[75]  Min Zhang,et al.  Nox4 Is a Protective Reactive Oxygen Species Generating Vascular NADPH Oxidase , 2012, Circulation research.

[76]  S. Bodhankar,et al.  Cardioprotective Activity of Pongamia pinnata in Streptozotocin-Nicotinamide Induced Diabetic Rats , 2015, BioMed research international.

[77]  Hongting Zheng,et al.  Therapeutic Potential of Nrf2 Activators in Streptozotocin-Induced Diabetic Nephropathy , 2011, Diabetes.

[78]  Hongting Zheng,et al.  Nrf2 modulates contractile and metabolic properties of skeletal muscle in streptozotocin-induced diabetic atrophy. , 2013, Experimental cell research.

[79]  D. Stern,et al.  Understanding RAGE, the receptor for advanced glycation end products , 2005, Journal of Molecular Medicine.

[80]  S. Yuda,et al.  Diabetic cardiomyopathy: pathophysiology and clinical features , 2012, Heart Failure Reviews.

[81]  Yi Tan,et al.  Metallothionein deletion exacerbates intermittent hypoxia-induced renal injury in mice. , 2015, Toxicology letters.

[82]  M. Ishar,et al.  Ameliorative effect of Aegle marmelos leaf extract on early stage alloxan-induced diabetic cardiomyopathy in rats , 2011, Pharmaceutical biology.

[83]  A. Shah,et al.  Pivotal Role of a gp91phox-Containing NADPH Oxidase in Angiotensin II-Induced Cardiac Hypertrophy in Mice , 2002, Circulation.

[84]  A. Wen,et al.  Antioxidant and antiglycation properties of triterpenoid saponins from Aralia taibaiensis traditionally used for treating diabetes mellitus , 2010, Redox report : communications in free radical research.

[85]  Yi Tan,et al.  The Role of MicroRNAs in Diabetic Nephropathy , 2014, Journal of diabetes research.

[86]  Xiangrong Tian,et al.  New antioxidant and antiglycation active triterpenoid saponins from the root bark of Aralia taibaiensis. , 2012, Fitoterapia.

[87]  Wei Yu,et al.  Curcumin Protects Neonatal Rat Cardiomyocytes against High Glucose-Induced Apoptosis via PI3K/Akt Signalling Pathway , 2016, Journal of diabetes research.

[88]  Q. Ma,et al.  Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes. , 2009, Journal of molecular and cellular cardiology.

[89]  S. Chakrabarti,et al.  Preventive effects of North American Ginseng (Panax quinquefolius) on Diabetic Retinopathy and Cardiomyopathy , 2013, Phytotherapy research : PTR.

[90]  M. Thomson,et al.  Anti-diabetic and anti-oxidant potential of aged garlic extract (AGE) in streptozotocin-induced diabetic rats , 2015, BMC Complementary and Alternative Medicine.

[91]  陈军,et al.  Progress in Researches on the Pharmaceutical Mechanism and Clinical Application of Ginkgo Biloba Extract on Various Kinds of Diseases , 2006 .

[92]  M. Kong,et al.  C66 ameliorates diabetic nephropathy in mice by both upregulating NRF2 function via increase in miR-200a and inhibiting miR-21 , 2016, Diabetologia.

[93]  S. Reddy,et al.  The transcription factor NRF2 protects against pulmonary fibrosis , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[94]  Q. Ma.  Transcriptional responses to oxidative stress: pathological and toxicological implications. , 2010, Pharmacology & therapeutics.

[95]  L. Cai,et al.  Magnolia Extract (BL153) Protection of Heart from Lipid Accumulation Caused Cardiac Oxidative Damage, Inflammation, and Cell Death in High-Fat Diet Fed Mice , 2014, Oxidative medicine and cellular longevity.

[96]  L. Cai,et al.  Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation. , 2013, Journal of molecular and cellular cardiology.

[97]  D. Dettmer,et al.  Protective effects of Gingko biloba extract EGb 761 on myocardium of experimentally diabetic rats. I: ultrastructural and biochemical investigation on cardiomyocytes. , 1999, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[98]  J. Chen,et al.  The Receptor for Advanced Glycation End Products (RAGE) Is a Cellular Binding Site for Amphoterin , 1995, The Journal of Biological Chemistry.

[99]  K. Rahman,et al.  Dietary supplementation with aged garlic extract reduces plasma and urine concentrations of 8-iso-prostaglandin F(2 alpha) in smoking and nonsmoking men and women. , 2002, The Journal of nutrition.

[100]  F. Azizi,et al.  Effect of broccoli sprouts on insulin resistance in type 2 diabetic patients: a randomized double-blind clinical trial , 2012, International journal of food sciences and nutrition.

[101]  S. Factor,et al.  Capillary microaneurysms in the human diabetic heart. , 1980, The New England journal of medicine.

[102]  A. Al-Khadra,et al.  Nigella sativa Improves Glycemic Control and Ameliorates Oxidative Stress in Patients with Type 2 Diabetes Mellitus: Placebo Controlled Participant Blinded Clinical Trial , 2015, PloS one.

[103]  C. Liang,et al.  AGEs increased migration and inflammatory responses of adventitial fibroblasts via RAGE, MAPK and NF-kappaB pathways. , 2010, Atherosclerosis.

[104]  D. Mikhailidis,et al.  Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy , 2013, Diabetology & Metabolic Syndrome.

[105]  Dhiren P. Shah,et al.  ON OXIDATIVE STRESS AND DIABETIC COMPLICATIONS , 2013 .

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

[107]  Cardioprotective Role of Syzygium cumini Against Glucose-Induced Oxidative Stress in H9C2 Cardiac Myocytes , 2013, Cardiovascular Toxicology.

[108]  N. Ahmed,et al.  Antiglycation properties of aged garlic extract: possible role in prevention of diabetic complications. , 2006, The Journal of nutrition.

[109]  V. De Feo,et al.  Abroma augusta L. (Malvaceae) leaf extract attenuates diabetes induced nephropathy and cardiomyopathy via inhibition of oxidative stress and inflammatory response , 2015, Journal of Translational Medicine.