Antioxidative Effects of Natural Products on Diabetic Cardiomyopathy

Table 1

Effects of natural products on diabetic cardiomyopathy.

Name	Model	Dose	Target	Effect	Ref.
Sulforaphane	STZ-induced diabetic C57BL/6J mice	0.5 mg/kg/d, for 3 months	Nrf2	Cardiac oxidative damage ↓, inflammation ↓, hypertrophy ↓, fibrosis ↓, and dysfunction ↓	[56]
	HFD/STZ-induced diabetic C57BL/6J mice	0.5 mg/kg/d, for 4 months	Nrf2	Cardiac LKB1/AMPK pathway ↑, lipotoxicity ↓, fibrosis ↓, inflammation ↓, and dysfunction ↓	[57]
	HFD/STZ-induced diabetic C57BL/6J WT and Nrf2 KO mice and 129 s WT and Mt KO mice	0.5 mg/kg/d, for 4 months	Nrf2	Cardiac MT ↑, HO-1 ↑, NQO1 ↑, oxidative damage ↓, inflammation ↓, fibrosis ↓, hypertrophy ↓, and dysfunction ↓	[31]
Curcumin	STZ-induced diabetic Wistar rats	200 mg/kg/d, for 6 weeks	Free radicals	Myocardial capillary sclerosis ↓	[61]
	STZ-induced diabetic Wistar rats	100 or 200 mg/kg/d, for 16 weeks	AGEs/RAGE, NOX subunits, and SOD	Myocardial dysfunction ↓, cardiac fibrosis ↓, AGE accumulation ↓, oxidative stress ↓, inflammation ↓, apoptosis ↓, phosphorylation of Akt and GSK-3β ↑	[62]
	High glucose-treated neonatal rat cardiomyocytes	10 μmol/L, for 30 min	NOX subunits	HG-induced oxidative stress and apoptosis ↓	[65]
	STZ-induced diabetic Sprague-Dawley rats	100 mg/kg/d, for 8 weeks	PKC, NOX subunits, and TGF-β	Blood glucose ↓, cardiac oxidative stress ↓, lipid peroxidation ↓, antioxidant activity ↑, cardiomyocyte hypertrophy ↓, myocardial fibrosis ↓, left ventricular dysfunction ↓	[63]
	STZ-induced diabetic rats	20 mg/kg/d, for 45 days	HO-1 ↑	Expression of ANP, MEF2A, MEF2C, and P300 ↓, left ventricular function ↑	[64]
Icariin	STZ-induced diabetic Sprague-Dawley rats	30 or 120 ml/kg/d, for 8 weeks	Mitochondrial ROS	Myocardial collagen deposition ↓, ventricular hypertrophy ↓, body weight loss ↓, cardiac function ↑	[68]
Flos Puerariae	STZ-induced diabetic C57BL/6J mice	100 or 200 mg/kg/d, for 10 weeks	Expression of NOX and the antioxidants SOD and GSH	Cardiac remodeling↓, apoptotic cardiac cell death ↓	[69]
Betanin	High fructose feed-induced diabetic Sprague-Dawley rats	25 or 100 mg/kg/d, for 60 days	AGEs/RAGE, oxidative stress, and NF-κB	Cardiac fibrosis ↓, TGF-β1 and CTGF ↓	[70]
Chrysin	STZ-induced diabetic Wistar rats	60 mg/kg, for 28 days	PPAR-γ	Cardiac CAT ↑, MnSOD ↑, GSH ↑, AGEs/RAGE ↓, oxidative stress ↓, apoptosis ↓, cardiac dysfunction ↓	[71]
Aralia taibaiensis	High glucose-treated H9c2 cells	25, 50, or 75 μg/ml	Nrf2	Apoptosis ↓, ROS ↓, and oxidative damage ↓	[75]
Magnolia plant extract	High-fat diet-induced obese C57BL/6 mice	BL153 at 5 or 10 mg/kg/d, for 24 weeks	Not indicated	Cardiac lipid accumulation ↓, inflammation ↓, oxidative stress ↓, and apoptosis ↓.	[76]
	High-fat diet-induced obese C57BL/6 mice	4-O-methylhonokiol at 0.5 or 1.0 mg/kg/d, for 24 weeks	Nrf2/HO-1, Akt2	Cardiac oxidative stress ↓, lipid accumulation ↓, hypertrophy ↓, and dysfunction ↓	[78]
Abroma augusta L. leaf	STZ/nicotinamide-induced type 2 diabetic rats	100 or 200 mg/kg/d, for 4 weeks	Not indicated	Hyperglycemia ↓, hyperlipidemia ↓, membrane disintegration ↓, cardiac oxidative stress and oxidative stress-induced cell death ↓	[80]
Aegle marmelos leaf extract	Alloxan-induced diabetic rats	200 mg/kg/d, for 14 days	GSH, CAT, and SOD	Cardiac necrosis ↓ and inflammation ↓	[81]
Dendrobium officinale extract	STZ-induced Kunming diabetic mice	300 mg/kg/d, for 8 weeks	SOD	Cardiac MDA ↓, lipid accumulation ↓, and the expression of inflammatory and fibrotic factors ↓	[82]
Fermented rooibos extract	H2O2-treated cardiomyocytes isolated from the hearts of STZ-induced rats	1 or 10 μg/ml, for 6 hours	GSH	ROS generation ↓, apoptosis ↓	[84]
Ficus racemosa stem bark extract	STZ-induced diabetic Wistar rats	200 or 400 mg/kg/d, for 8 weeks	SOD	Cardiac MDA ↓	[85]
Ginkgo biloba	STZ-induced diabetic rats	100 mg/kg/d, for 3 months	SOD	Creatine kinase activity ↑, myofibril loss ↓, reduction of myocyte diameter ↓	[88]
Kalpaamruthaa	HFD/STZ-induced diabetic Sprague-Dawley rats	200 mg/kg/d, for 28 days	NOX, eNOS	Cardiac lipid peroxides ↓, proinflammatory cytokines ↓, matrix metalloproteinase-2 and matrix metalloproteinase-9 ↓, cardiac remodeling ↓	[89]
	HFD/STZ-induced diabetic Sprague-Dawley rats	200 mg/kg/d, for 28 days	PKC-β/Akt	Cardiac lipid accumulation ↓, chromatin condensation and marginalization ↓, hepatic antioxidants ↑, insulin resistance ↓, blood glucose ↓	[90]
	HFD/STZ-induced diabetic Sprague-Dawley rats	200 mg/kg/d, for 28 days	Cardiac expression of protease-activated receptor-1	Pancreatic antioxidants ↑, pancreatic lipid peroxides and carbonyl content ↓, markers of injury in the plasma, heart, and liver↓	[91]
North American ginseng	STZ-induced diabetic C57BL/6J type 1 diabetic mice or db/db type 2 diabetic mice	200 mg/kg/d, for 2 or 4 months	Oxidative stress	Cardiac extracellular matrix proteins and vasoactive factors ↓, hypertrophy ↓, dysfunction ↓	[92]
Pongamia pinnata	STZ/nicotinamide-induced type 2 diabetic rats	100 mg/kg/d, for 4 months	Not indicated	Cardiac SOD ↑, GSH ↑, MDA ↓, remodeling, dysfunction ↓, biomarkers for cardiac injury ↓, blood glucose ↓	[93]
Syzygium cumini	High glucose-treated H9c2 cells	9 μg/ml	ROS	Hypertrophy ↓, accumulation of extracellular matrix ↓	[94]

AGEs: advanced glycosylation end products; AMPK: 5′ AMP-activated protein kinase; ANP: atrial natriuretic peptide; CAT: catalase; CTGF: connective tissue growth factor; eNOS: endothelial nitric oxide synthase; GSH: glutathione; GSK-3β: glycogen synthase kinase 3 beta; HFD: high-fat diet; HG: high glucose; HO-1: heme oxygenase-1; KO: knockout; LKB1: liver kinase B1; MDA: malondialdehyde; MEF2A: myocyte-specific enhancer factor 2A; MEF2C: myocyte-specific enhancer factor 2C; MT: metallothionein; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NOX: NADPH oxidase; NQO1: NADPH quinone oxidoreductase; Nrf2: nuclear factor erythroid 2-related factor 2; PKC-β: protein kinase C-beta; PPAR-γ: peroxisome proliferator-activated receptor-gamma; RAGE: receptor for AGEs; ROS: reactive oxygen species; SOD: superoxide dismutase; STZ: streptozotocin; WT: wild type; ↑: activation or improvement; ↓: inhibition or downregulation.