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

Abstract

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.

Keywords: bixin; cardiovascular risk; curcumin; diabetes mellitus; lycopene; oxidative stress.

Figure 1

Temporal changes in glycemia (A); triacylglycerol (B); and total-cholesterol (C) plasma levels in STZ-diabetic rats treated for 50 days with yoghurt enriched with curcumin and carotenoids, individually or as mixtures. Values are expressed as means ± SEM, n = 10. Differences between groups were considered significant at p < 0.05 and were analyzed by one-way ANOVA followed by a Student-Newman-Keuls test. Differences in the same group relative to day 0 were analyzed using a paired Student’s t test. #, different compared to day 0 (p < 0.05).

Figure 2

Plasma levels of high-density lipoprotein (HDL) cholesterol (A) thiobarbituric acid reactive substances (TBARS) (B); oxidized low-density lipoprotein (ox-LDL) (C); and paraoxonase 1 (PON1) activity (D) of STZ-diabetic rats after 50 days of treatment with yoghurt enriched with curcumin and carotenoids, individually or as mixtures. Values are expressed as means ± SEM, n = 10. Differences between groups were considered significant at p < 0.05 and were analyzed with one-way ANOVA followed by Student-Newman-Keuls test. a, different compared to NYOG; b, different compared to DYOG; c, different compared to DINS; d, different compared to DC; e, different compared to DB (p < 0.05).

Figure 3

Hepatic levels of TBARS (A); and carbonyl protein groups (B) of STZ-diabetic rats after 50 days of treatment with yoghurt enriched with curcumin and carotenoids, individually or as mixtures. Values are expressed as means ± SEM, n = 10. Differences between groups were considered significant at p < 0.05 and were analyzed with one-way ANOVA followed by Student-Newman-Keuls test. a, different compared to NYOG; b, different compared to DYOG; c, different compared to DINS; d, different compared to DC; e, different compared to DB; f, different compared to DCB; g, different compared to DL (p < 0.05).

Figure 4

Hepatic activities of superoxide dismutase (SOD) (A); catalase (CAT) (B); glutathione peroxidase (GSH-Px) (C); and non-protein sulfhydryl groups (NPSH) levels (D) of STZ-diabetic rats after 50 days of treatment with yoghurt enriched with curcumin and carotenoids, individually or as mixtures. Values are expressed as means ± SEM, n = 10. Differences between groups were considered significant at p < 0.05 and were analyzed with one-way ANOVA followed by Student-Newman-Keuls test. a, different compared to NYOG; b, different compared to DYOG; c, different compared to DINS; d, different compared to DC; e, different compared to DB; f, different compared to DCB; g, different compared to DL (p < 0.05).