Curcumin improves the metabolic syndrome in high-fructose-diet-fed rats: role of TNF-α, NF-κB, and oxidative stress.

This study aimed to investigate effects of curcumin on high fructose diet (HFD)-induced metabolic syndrome (MetS) in rats and the possible mechanisms involved. MetS was induced in male albino rats (n = 20), over 8 weeks, by 65% HFD. For 8-week experiment period, rats were assigned to 2 equal groups: curcumin-treated rats received curcumin (200 mg/kg, p.o, once daily) along with HFD, and untreated rats were fed with HFD only. We evaluated body mass (BM), systolic blood pressure (SBP), homeostasis model assessment of insulin resistance (HOMA-IR), and serum levels of glucose, insulin, leptin, total cholesterol (TC), triglycerides (TGs), uric acid, malondialdehyde (MDA; lipid peroxidation product), and tumor necrosis factor-α (TNF-α; inflammatory cytokine), and serum catalase (endogenous antioxidant) activity and immunohistochemical expression of nuclear factor κB (NF-κB; inflammation-related transcription factor) in hepatocytes. HFD produced increases in BM, SBP, HOMA-IR, and serum levels of glucose, insulin, leptin, TC, TGs, uric acid, MDA, and TNF-α, a decrease in catalase activity, and strong positive expression of NF-κB in hepatocytes. Curcumin, in presence of HFD, produced significant improvements in all glucose and fat metabolism parameters, and in oxidative stress and inflammation biomarkers. Curcumin may potentially be useful in the treatment of MetS through its ability to modulate oxidation stress status and inflammation cascades.

Combination of Sitagliptin and Insulin against Type 2 Diabetes Mellitus with Neuropathy in Rats: Neuroprotection and Role of Oxidative and Inflammation Stress.

AIMS: The present study evaluated the effects of sitagliptin-insulin against type 2 diabetes mellitus with neuropathy in rats and possible neuroprotective mechanisms. METHODS: Diabetes was induced in 32 adult male albino rats by 6-week high-fat high-sugar diet followed by streptozotocin 30 mg/kg intraperitoneal injection. For 4 weeks thereafter, diabetic rats were divided into 4 groups, each group receiving one of the following daily: vehicle (untreated diabetic), insulin 10 IU/kg SC, sitagliptin 30 mg/kg PO or sitagliptin-insulin. We assessed systolic blood pressure (SBP), blood glucose, serum insulin and advanced glycation end-products (AGEs), thermal hyperalgesia and sciatic nerve tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) and sciatic histopathology. RESULTS: Compared to untreated and insulin-treated groups, sitagliptin decreased SBP, serum AGEs and sciatic MDA and TNF-α, and increased serum insulin and sciatic SOD, but insulin decreased blood glucose more. Sitagliptin-insulin (greater than sitagliptin or insulin alone) superiorly decreased and increased the above respective parameters, and ameliorated hyperalgesia and sciatic histopathological changes, but was similar to insulin in decreasing blood glucose, and similar to sitagliptin in rising serum insulin. CONCLUSIONS: Sitagliptin-insulin combination produced hypoglycemic and neuroprotective effect and ameliorated hyperalgesia, oxidative stress and inflammation more than either drug alone. This combination might have clinical efficacy in uncontrolled type 2 diabetes with neuropathy.