Piperine, a Natural Bioenhancer, Nullifies the Antidiabetic and Antioxidant Activities of Curcumin in Streptozotocin-Diabetic Rats

Abstract

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.

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

“…The overproduction of ROS and the decreased levels of antioxidant defenses contribute to the establishment of oxidative stress in DM (Maritim, Sanders, & Watkins, ). In agreement with this, DYOG rats had high levels of oxidative damage biomarkers, including plasma TBARS (Figure a) and hepatic PCO (Figure b) and low activity of antioxidant enzymes (Figure ), corroborating the results from previous studies (Arcaro et al, ; Assis et al, ). Structural modifications due to oxidative or glycative stress may explain the low activity of antioxidant enzymes in diabetes (Pigeolet et al, ; Yan & Harding, ).…”

“…The present study reinforces that yoghurt can be used for the oral administration of curcumin and solved the problem of low curcumin solubility in water, avoiding its administration in oil, which could negatively impact the lipid profile or even impair the beneficial effects of curcumin. Subsequent studies from our laboratory confirm the beneficial effects of curcumin on DM when administered via yoghurt (Arcaro et al, ; Assis et al, ). Finally, Palma et al did not observe the additive effect on glycemia reduction nor on biomarkers related to hepatic and renal damage and LPO (plasma) when compared with the treatment with insulin alone (4 U/day).…”

“…The antidiabetic activity of curcumin has been well documented in both type 1 (Gutierres et al, ) and type 2 (Shao et al, ) DM models, improving not only the levels of glycemia but also those of dyslipidemia and tissue damage markers. Previous studies carried out by groups from our laboratory (Arcaro et al, ; Assis et al, ) and by others (Ghosh, Bhattacharyya, Rashid, & Sil, ) have found that the treatment of diabetic rats with curcumin is able to reduce in vivo oxidative stress. These findings identify curcumin as a promising adjunct to insulin therapy for diabetes.…”

“…The treatment of STZ‐diabetic rats with 4‐U/day insulin is often used as an effective intervention for the control of glycemia levels and to normalize diabetic disturbances. This dose of insulin has been administered to diabetic rats as a positive control in previous studies by our laboratory (Arcaro et al, ; Assis et al, ; Gutierres et al, ) and also in studies by other groups using the experimental model of type 1 DM (Palma et al, ; Slaughter et al, ). In fact, STZ‐diabetic rats with initial glycemia values of approximately 470 mg/dl, when treated with 4‐U/day insulin, they had a biomarker profile practically identical to that of normal rats.…”

Dietary Antioxidants in Experimental Models of Liver Diseases

“…Curcumin is known to have low bioavailability when administered orally. Arcaro et al [23] used piperine (inhibitor of hepatic and intestinal absorption) together with curcumin. Even in the presence of piperine, antidiabetic and antioxidant activity of curcumin was not altered.…”