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. TheCmax⁡and the time to reachCmax⁡(tmax⁡) 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.

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.

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. 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. 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. 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.

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 gluthatione 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.

We investigated the effects of prolonged treatment of diabetic rats with curcumin-supplemented yoghurt on the physiological and biochemical changes associated with diabetes mellitus. An established metabolic cage model was used to assess these changes in three groups of streptozotocin-diabetic rats which had been administered, by gavage, curcumin blended into yoghurt in the doses of 30, 60 and 90 mg/kg body weight (BW) per d (groups DC₃₀, DC₆₀, DC₉₀) for 31 d. One group of non-diabetic rats was also treated with 90 mg/kg BW per d curcumin (NDC90). Three control groups of diabetic animals received water (DW), yoghurt (DY) and insulin at 27·78 μmol/d by subcutaneous injection (DI). Also, two groups of non-diabetic animals received water (NDW) and yoghurt (NDY). Groups DI and DC90 exhibited significant falls, relative to DW and DY, in food and water intake, urine volume, glycaemia, urinary urea and glucose, proteinuria, serum TAG and activities of aspartate and alanine aminotransferases, and higher hepatic glycogen and BW. These improvements were greater in DI than in DC90. No difference was observed in the serum levels of total cholesterol or HDL-cholesterol, or in the masses of adipose and muscular tissues, between DC90 and DW or DY. Moreover, the improvements in curcumin-treated rats, relative to DW and DY, were significant and dose-dependent. The NDC90 group also showed no difference from the NDW or NDY groups, in any of the markers for diabetes. In conclusion, curcumin mixed into yoghurt at the highest dose tested exhibited anti-diabetic activity, improving significantly most of the markers assessed in this study.