Curcumin combined with metformin decreases glycemia and dyslipidemia, and increases paraoxonase activity in diabetic rats.

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.

Curcumin improves the effect of a reduced insulin dose on glycemic control and oxidative stress in streptozotocin-diabetic rats.

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.

Insulin treatment reverses the increase in atrogin-1 expression in atrophied skeletal muscles of diabetic rats with acute joint inflammation.

BACKGROUND: The aim of this study was to evaluate the changes in biomarkers of skeletal muscle proteolysis (atrogin-1, muscle RING finger-1 protein [MuRF-1]) and inflammation (nuclear factor kappa-B) in skeletal muscles of rats under two catabolic conditions, diabetes mellitus (DM) and acute joint inflammation, and the effects of insulin therapy. MATERIALS AND METHODS: Male Wistar rats were divided into groups without diabetes - normal (N), saline (NS), or ι-carrageenan (NCa) injection into the tibiotarsal joint - and groups with diabetes - diabetes (D), plus insulin (DI), saline (DS), or ι-carrageenan (DCa) injection into the tibiotarsal joint, or ι-carrageenan injection and treatment with insulin (DCaI). Three days after ι-carrageenan injection (17 days after diabetes induction), tibialis anterior (TA) and soleus (SO) skeletal muscles were used for analysis. RESULTS: DM alone caused a significant decrease in the mass of TA and SO muscles, even with low levels of atrogenes (atrogin-1, MuRF-1), which could be interpreted as an adaptive mechanism to spare muscle proteins under this catabolic condition. The loss of muscle mass was exacerbated when ι-carrageenan was administered in the joints of diabetic rats, in association with increased expression of atrogin-1, MuRF-1, and nuclear factor kappa-B. Treatment with insulin prevented the increase in atrogin-1 (TA, SO) and the loss of muscle mass (SO) in diabetic-carrageenan rats; in comparison with TA, SO muscle was more responsive to the anabolic actions of insulin. CONCLUSION: Acute joint inflammation overcame the adaptive mechanism in diabetic rats to prevent excessive loss of muscle mass, worsening the catabolic state. The treatment of diabetic-carrageenan rats with insulin prevented the loss of skeletal muscle mass mainly via atrogin-1 inhibition. Under the condition of DM and inflammation, muscles with the prevalence of slow-twitch, type 1 fibers were more responsive to insulin treatment, recovering the ability to grow.

Combined Effects of Curcumin and Lycopene or Bixin in Yoghurt on Inhibition of LDL Oxidation and Increases in HDL and Paraoxonase Levels in Streptozotocin-Diabetic Rats.

Combination therapy using natural antioxidants to manage diabetes mellitus and its complications is an emerging trend. The aim of this study was to investigate the changes promoted by treatment of streptozotocin (STZ)-diabetic rats with yoghurt enriched with the bioactives curcumin, lycopene, or bixin (the latter two being carotenoids). Antioxidants were administered individually, or as mixtures, and biomarkers of metabolic and oxidative disturbances, particularly those associated with cardiovascular risk, were assessed. Treatment of STZ-diabetic rats with natural products individually decreased glycemia, triacylglycerol, total-cholesterol, oxidative stress biomarkers, including oxidized low-density lipoprotein (ox-LDL), and increased the activities of antioxidant enzymes. Individual carotenoids increased both high-density lipoprotein (HDL) and paraoxonase levels, whereas curcumin increased only paraoxonase. Treatments with mixtures of curcumin and lycopene or bixin had combined effects, decreasing biomarkers of carbohydrate and lipid disturbances (curcumin effect), increasing the HDL levels (carotenoids effects) and mitigating oxidative stress (curcumin and carotenoids effects). The combined effects also led to prevention of the LDL oxidation, thereby mitigating the cardiovascular risk in diabetes. These findings provide evidence for the beneficial effect of curcumin and carotenoid mixtures as a supplementation having antioxidant and antiatherogenic potentials, thus appearing as an interesting strategy to be studied as a complementary therapy for diabetic complications.

Curcumin Pharmacokinetic and Pharmacodynamic Evidences in Streptozotocin-Diabetic Rats Support the Antidiabetic Activity to Be via Metabolite(s).

This study measures the curcumin concentration in rat plasma by liquid chromatography and investigates the changes in the glucose tolerance and insulin sensitivity of streptozotocin-diabetic rats treated with curcumin-enriched yoghurt. The analytical method for curcumin detection was linear from 10 to 500 ng/mL. The C max⁡ and the time to reach C max⁡ (t max⁡) of curcumin in plasma were 3.14 ± 0.9 µg/mL and 5 minutes (10 mg/kg, i.v.) and 0.06 ± 0.01 µg/mL and 14 minutes (500 mg/kg, p.o.). The elimination half-time was 8.64 ± 2.31 (i.v.) and 32.70 ± 12.92 (p.o.) minutes. The oral bioavailability was about 0.47%. Changes in the glucose tolerance and insulin sensitivity were investigated in four groups: normal and diabetic rats treated with yoghurt (NYOG and DYOG, resp.) and treated with 90 mg/kg/day curcumin incorporated in yoghurt (NC90 and DC90, resp.). After 15 days of treatment, the glucose tolerance and the insulin sensitivity were significantly improved in DC90 rats in comparison with DYOG, which can be associated with an increase in the AKT phosphorylation levels and GLUT4 translocation in skeletal muscles. These findings can explain, at least in part, the benefits of curcumin-enriched yoghurt to diabetes and substantiate evidences for the curcumin metabolite(s) as being responsible for the antidiabetic activity.

Piperine, a natural bioenhancer, nullifies the antidiabetic and antioxidant activities of curcumin in streptozotocin-diabetic rats.

Knowing that curcumin has low bioavailability when administered orally, and that piperine has bioenhancer activity by inhibition of hepatic and intestinal biotransformation processes, the aim of this study was to investigate the antidiabetic and antioxidant activities of curcumin (90 mg/kg) and piperine (20 or 40 mg/kg), alone or co-administered, incorporated in yoghurt, in streptozotocin (STZ)-diabetic rats. The treatment for 45 days of STZ-diabetic rats with curcumin-enriched yoghurt improved all parameters altered in this experimental model of diabetes: the body weight was increased in association with the weight of skeletal muscles and white adipose tissues; the progressive increase in the glycemia levels was avoided, as well as in the glycosuria, urinary urea, dyslipidemia, and markers of liver (alanine and aspartate aminotransferases and alkaline phosphatase) and kidney (urinary protein) dysfunction; the hepatic oxidative stress was decreased, since the activities of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were increased, and the levels of malondialdehyde and protein carbonyl groups were reduced. The dose of 20 mg/kg piperine also showed antidiabetic and antioxidant activities. The treatment of STZ-diabetic rats with both curcumin and 20 mg/kg piperine in yoghurt did not change the antidiabetic and antioxidant activities of curcumin; notably, the treatment with both curcumin and 40 mg/kg piperine abrogated the beneficial effects of curcumin. In addition, the alanine aminotransferase levels were further increased in diabetic rats treated with curcumin and 40 mg/kg piperine in comparison with untreated diabetic rats. These findings support that the co-administration of curcumin with a bioenhancer did not bring any advantage to the curcumin effects, at least about the antidiabetic and antioxidant activities, which could be related to changes on its biotransformation.

Salacia campestris root bark extract: peroxidase inhibition, antioxidant and antiradical profile / Salacia campestris extrato da casca da raiz: inibição da peroxidase, antioxidante e anti-radicalar perfil

Reactive oxygen species (ROS) and free radical species have been implicated in initiating or accompanying many diseases in living organisms; there is thus, a continual need for antioxidants molecules to inactivate ROS/free radicals. Many studies of plants crude extracts have demonstrated free-radical scavenging and antioxidant action. Salacia species have long been used, in several countries, as traditional medicines against certain diseases and for their anti-inflammatory properties. In this study, Salacia campestris Walp (Hippocrateaceae) root bark ethanol extract (ScEtOH) was assessed for its ability to scavenge free radicals and reactive oxygen species; the results were expressed as percentage inhibition of the active species. ScEtOH was efficient against studied species: DPPH radical (obtained inhibition = 30 percent), ABTSò+ (IC50 = 1.8±0.8 μg/mL), HOCl (IC50 = 1.7 ± 0.1 μg/mL), O2ò- (obtained inhibition = 32 percent), and NOò (obtained inhibition = 18 percent). Peroxidase activity inhibition was evaluated through the guaiacol oxidation reaction catalyzed by hemin, HRP and myeloperoxidase (MPO); data showed that ScEtOH at 10 μg/mL led to 54 and 51 percent of inhibition, respectively, for the hemin and HRP systems. In the MPO system, ScEtOH promoted a 50 percent inhibition at 8.9 μg/mL, whereas quercetin, a powerful MPO inhibitor, inhibited this system at 1.35 μg/mL.

Espécies reativas do oxigênio (ERO) e radicais livres estão relacionados ao início ou à exacerbação de muitas doenças em organismos vivos; existindo portanto uma necessidade contínua por moléculas antioxidantes que inativem as ERO e radicais livres. Muitos estudos com extratos brutos de plantas têm demonstrado propriedades antioxidantes e sequestradoras de radicais livres. Espécies de Salacia são utilizadas, em muitos países, como remédio tradicional contra certas doenças e por suas propriedades antiinflamatórias. Neste estudo, o extrato bruto etanólico da casca da raiz da Salacia campestris Walp (Hippocrateaceae) foi avaliado quanto à sua habilidade em seqüestrar radicais livres e espécies reativas do oxigênio; os resultados são expressos como porcentagem de inibição das espécies ativas. ScEtOH mostrou-se eficiente frente as espécies estudadas: radical DPPH (inibição obtida = 30 por cento), ABTSò+ (IC50 = 1,8±0,8 μg/mL), HOCl (IC50 = 1,7 ± 0,1 μg/mL), O2ò- (inibição obtida = 32 por cento), and NOò (inibição obtida = 18 por cento). A inibição da atividade peroxidásica foi avaliada através da oxidação do guaiacol catalisada pela hemina, HRP e mieloperoxidase (MPO); os dados mostram que 10 μg/mL de ScEtOH promovem 54 e 51 por cento de inibição, respectivamente para os sistemas da hemina e da HRP. No sistema da MPO, ScEtOH promoveu 50 por cento de inibição na dose de 8,9 μg/mL, enquanto a quercetina, um potente inibidor da MPO promoveu tal inibição com 1,35 μg/mL.