Background Combination of current antidiabetic agents with natural antioxidants to manage diabetes mellitus and its complications has appeared as an emerging trend. Curcumin, a yellow pigment isolated from Curcuma longa rhizomes, has gained attention due to its beneficial effects in controlling the disturbances observed in diabetes mellitus. The purpose of this study was to investigate if yoghurt enriched with curcumin and metformin, individually or as mixtures, ameliorates physiometabolic parameters, glycoxidative stress biomarkers, and paraoxonase 1 (PON 1) activity in diabetic rats. Methods Streptozotocin-diabetic rats (6-week-old Wistar rats) were treated for 30 days with curcumin and metformin, isolated or as mixtures in yoghurt (10 rats/group). After treatments, the plasma levels of glucose, triacylglycerol, cholesterol, thiobarbituric acid reactive substances (TBARS, a biomarker of lipid oxidation), fluorescent advanced glycation end products (AGEs), and the activity of PON 1, an antioxidant enzyme were assessed. Data were analyzed using one-way analysis of variance (ANOVA) followed by Student–Newman–Keuls test. Results Treatment of diabetic rats with curcumin or metformin alone decreased the plasma levels of glucose, triacylglycerol, cholesterol, TBARS, and fluorescent AGEs, as well as increased the activity of PON 1. The combination of metformin with curcumin further decreased dyslipidemia and TBARS levels in diabetic rats, indicating synergy, and maintained the high levels of PON 1. Conclusion These findings indicated that curcumin combined with metformin may act synergistically on dyslipidemia and oxidative stress, as well as increased PON 1 levels. Therefore, it might be a promising strategy for combating diabetic complications, mainly the cardiovascular events.

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Insulin with natural antioxidants is emerging as a combination treatment for diabetes mellitus that attempts to exert effective glycemic control without adverse effects. The present study aimed to investigate the additive effects on metabolic disturbances, oxidative damage, and antioxidant defenses in streptozotocin-diabetic rats treated with curcumin and a reduced insulin dose. The best results were obtained in the treatment of diabetic rats with 4-U/day insulin; however, the glycemia levels in these rats were lower than those in normal rats, indicating a risk of hypoglycemia. Isolated treatments using curcumin or insulin in a reduced dose (1 U/day) decreased glycemia, dyslipidemia, and biomarkers of liver and kidney damage and increased the activity of hepatic antioxidants (superoxide dismutase and glutathione peroxidase), however, only to a lesser extent than 4-U/day insulin, without improvements in catalase activity or plasma lipid peroxidation. Decreases in glycemia, dyslipidemia, and tissue damage markers were more evident in the curcumin + 1-U/day insulin treatment than those seen in isolated treatments. The activity of hepatic antioxidants, including catalase, was further increased, and biomarkers of oxidative damage were decreased. Curcumin with a reduced insulin dose appears to be a promising strategy for combating the complications associated with diabetes and oxidative stress.

Introduction Oxidative stress and exacerbated generation of advanced glycation end products (AGEs) participate in the onset of diabetic complications. Lycopene is a potent antioxidant; evidence accounts for its ability to mitigate diabetic disturbances, including the deleterious events of advanced glycation. Therefore, this carotenoid has emerged as a candidate to be used in combination with antidiabetic drugs, such as metformin, attempting to counteract the glycoxidative stress. This study investigated the effects of the treatments with lycopene or metformin, alone or in combination, on glycoxidative stress biomarkers and antioxidant defenses in diabetic rats. Methods Streptozotocin-induced diabetic rats were treated for 35 days with lycopene (45 mg/kg) or metformin (250 mg/kg), alone or as mixtures in yoghurt. Plasma levels of glucose, triglycerides, cholesterol, thiobarbituric acid reactive substances and protein carbonyl groups (biomarkers of oxidative damage), fluorescent AGEs (biomarkers of advanced glycation), and paraoxonase 1 activity (antioxidant enzyme) were assessed. Changes in the hepatic and renal levels of glycoxidative damage biomarkers and the activities of antioxidant enzymes were investigated. Results The combination of lycopene with metformin maintained the beneficial effects of the isolated treatments, improving the glucose tolerance and lipid profile, lessening biomarkers of oxidative damage, and increasing the paraoxonase 1 activity. Besides, the combined therapy caused further decreases in postprandial glycemia, plasma levels of cholesterol and AGEs, avoided lipid peroxidation (plasma, kidney), and increased antioxidant defenses, mainly the activity of superoxide dismutase (liver, kidney), indicating the maintenance of the lycopene effects. Conclusion Lycopene combined with metformin may act synergistically in the control of postprandial glycemia, dyslipidemia and glycoxidative stress, as well as increased antioxidant defenses, arising as a promising therapeutic strategy to mitigate diabetic complications.

Both oxidative stress and the exacerbated generation of advanced glycation end products (AGEs) have crucial roles in the onset and progression of diabetic complications. Curcumin has antioxidant and antidiabetic properties; its combination with compounds capable of preventing the advanced glycation events, such as aminoguanidine, is an interesting therapeutic option to counteract diabetic complications. This study is aimed at investigating the effects of treatments with curcumin or aminoguanidine, alone or in combination, on metabolic alterations in streptozotocin-diabetic rats; the focus was mainly on the potential of these bioactive compounds to oppose the glycoxidative stress. Curcumin (90 mg/kg) or aminoguanidine (50 and 100 mg/kg), alone or in combination, slightly decreased glycemia and the biomarkers of early protein glycation, but markedly decreased AGE levels (biomarkers of advanced glycation) and oxidative damage biomarkers in the plasma, liver, and kidney of diabetic rats. Some novel insights about the in vivo effects of these bioactive compounds are centered on the triggering of cytoprotective machinery. The treatments with curcumin and/or aminoguanidine increased the activities of the antioxidant enzymes (paraoxonase 1, superoxide dismutase, and catalase) and the levels of AGE detoxification system components (AGE-R1 receptor and glyoxalase 1). In addition, combination therapy between curcumin and aminoguanidine effectively prevented dyslipidemia in diabetic rats. These findings demonstrate the combination of curcumin (natural antioxidant) and aminoguanidine (prototype therapeutic agent with anti-AGE activity) as a potential complementary therapeutic option for use with antihyperglycemic agents, which may aggregate beneficial effects against diabetic complications.