Synthesis and anti-inflammatory activity of three nitro chalcones.

The aim of this study was to synthesize three nitro substituted chalcones and to evaluate their anti-inflammatory activity in the model of carrageenan induced edema in rats. The nitro chalcone were prepared by aldol condensation using of mechanical agitation and environmentally friendly solvents with 72-73% yields in approximately 2h. The three structures were evaluated on biological activity at dose of 200mg/kg and they showed anti-inflammatory protective effect by both oral and intraperitoneal administration, this effect was time dependent.

Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats.

BACKGROUND: Traditional plant treatment for diabetes has shown a surging interest in the last few decades. Therefore, the purpose of this study was to assess the hypoglycemic effect of the aqueous extract of C. papaya leaves in diabetic rats. Several studies have reported that some parts of the C. papaya plant exert hypoglycemic effects in both animals and humans. METHODS: Diabetes was induced in rats by intraperitoneal administration of 60 mg/kg of streptozotocin (STZ). The aqueous extract of C. papaya was administered in three different doses (0.75, 1.5 and 3 g/100 mL) as drinking water to both diabetic and non-diabetic animals during 4 weeks. RESULTS: The aqueous extract of Carica papaya (0.75 g and 1.5 g/100 mL) significantly decreased blood glucose levels (p<0.05) in diabetic rats. It also decreased cholesterol, triacylglycerol and amino-transferases blood levels. Low plasma insulin levels did not change after treatment in diabetic rats, but they significantly increased in non-diabetic animals. Pancreatic islet cells were normal in non-diabetic treated animals, whereas in diabetic treated rats, C. papaya could help islet regeneration manifested as preservation of cell size. In the liver of diabetic treated rats, C. papaya prevented hepatocyte disruption, as well as accumulation of glycogen and lipids. Finally, an antioxidant effect of C. papaya extract was also detected in diabetic rats. CONCLUSIONS: This study showed that the aqueous extract of C. papaya exerted a hypoglycemic and antioxidant effect; it also improved the lipid profile in diabetic rats. In addition, the leaf extract positively affected integrity and function of both liver and pancreas.

Synergistic Herb-Herb Interaction of the Antinociceptive and Anti-Inflammatory Effects of Syzygium aromaticum and Rosmarinus officinalis Combination.

The use of alternative medicine to treat pain has been increased, and the combination of several medicinal plants for its relief is a common practice in traditional medicine. The present study is aimed at determining whether a combination of Syzygium aromaticum (S. aromaticum) and Rosmarinus officinalis L. (R. officinalis) potentiates their antinociceptive and anti-inflammatory effects. These effects were explored using the formalin and carrageenan assays in rats, respectively. Animals received local pretreatment with S. aromaticum oil or R. officinalis ethanolic extract (0.1-100 µg/paw) alone or combined in a 1 : 1 rate. Concentration-response curves were built to compare pharmacological responses after an individual administration of S. aromaticum, R. officinalis, or their combination. The pharmacological interaction was investigated by an isobolographic study using the EC50 of each component in a fixed 1 : 1 ratio. S. aromaticum and R. officinalis administered alone showed significant and concentration-dependent antinociceptive and anti-inflammatory effects, but R. officinalis was more potent than S. aromaticum in both the antinociceptive and anti-inflammatory effects (EC50 = 7.96 ± 0.6 µg/paw vs. EC50 = 41.6 ± 1.7 µg/paw; EC50 = 1.97 ± 0.3 µg/paw vs. EC50 = 26.9 ± 2.5 µg/paw, respectively). The isobolographic analysis of the combination of these species in a 1 : 1 ratio showed a synergistic interaction between S. aromaticum and R. officinalis since Z mix (experimental value) was lower than Z add (theoretical value) for both the antinociceptive effect (Z mix = 0.45 ± 0.1 < Z add = 24.8 ± 1.3) and the anti-inflammatory effect (Z mix = 5.2 ± 0.6 < Z add = 14.4 ± 2.2), suggesting a potentiation for both pharmacological effects. These results prove evidence of the efficacy of mixture herb-herb used in folk medicine for pain therapy. It also emphasizes the requirement of pharmacological studies to explore the efficacy and safety of herb interactions.

Synergistic antinociceptive interaction of Syzygium aromaticum or Rosmarinus officinalis coadministered with ketorolac in rats.

Syzygium aromaticum (L.) Merr. & L.M. Perry (Mirtaceae) and Rosmarinus officinalis L. (Lamiaceae) are both medicinal plants used for centuries to alleviate pain. The aim of the study was to demonstrate the therapeutic potential utility of herb-drug association of S. aromaticum essential oil or R. officinalis ethanolic extract coadministered with ketorolac. Antinociceptive pharmacological interaction was investigated by an isbolographic study using the formalin test in rats. Both alone and in combination with ketorolac; S. aromaticum and R. officinalis produced a dose-dependent antinociceptive response. To plot the isobologram, we used the effective dose 50 of each one component in a fixed 1:1 ratio. The isobolographic analysis showed that, in both combinations, ketorolac plus essential oil S. aromaticum and ketorolac plus ethanolic extract R. officinalis, the experimental value (Zexp) was lower than the theoretical value (Zadd). In addition, this study shows that eugenol, a metabolite present in S. aromaticum, and ursolic acid, a metabolite present in R. officinalis, also synergized the antinociceptive effect of ketorolac. While, the oleanolic acid present in both medicinal species did not show a synergistic antinociceptive effect in combination with ketorolac. No adverse effects were observed with these herb-drug interactions. These findings suggest that essential oil S. aromaticum and ethanolic extract R. officinalis could be useful in combination with ketorolac for the treatment of inflammatory pain.

No effect of magnesium supplementation on metabolic control and insulin sensitivity in type 2 diabetic patients with normomagnesemia.

There are limited and conflicting data from clinical trials concerning the beneficial effects of magnesium supplementation on diabetic patients. We investigated the effects of magnesium supplementation on metabolic control and insulin sensitivity in type 2 diabetic patients with normomagnesemia. A total of 98 normomagnesemic subjects with type 2 diabetes were enrolled in a randomized, crossover, double-blind, placebo-controlled trial. Participants were randomly assigned to receive magnesium lactate (360 mg elemental magnesium) or placebo for three months, followed by a three-month washout period. Treatment assignments were then reversed over an additional three months of follow-up. The primary endpoint was a reduction in fasting glucose and HbA1c. A total of 56 subjects completed the follow-up in the magnesium and placebo supplementation groups. Urinary magnesium excretion was increased following magnesium supplementation in the intervention group compared with the placebo group (p = 0.0002). Fasting glucose, HbA1c, insulin and HOMA-IR, as well as lipid profile, did not change significantly during treatment. We concluded that magnesium supplementation does not improve metabolic control or insulin sensitivity in diabetic subjects with normomagnesemia.

Differential effects of high-carbohydrate and high-fat diet composition on metabolic control and insulin resistance in normal rats.

The macronutrient component of diets is critical for metabolic control and insulin action. The aim of this study was to compare the effects of high fat diets (HFDs) vs. high carbohydrate diets (HCDs) on metabolic control and insulin resistance in Wistar rats. Thirty animals divided into five groups (n = 6) were fed: (1) Control diet (CD); (2) High-saturated fat diet (HSFD); (3) High-unsaturated fat diet (HUFD); (4) High-digestible starch diet, (HDSD); and (5) High-resistant starch diet (HRSD) during eight weeks. HFDs and HCDs reduced weight gain in comparison with CD, however no statistical significance was reached. Calorie intake was similar in both HFDs and CD, but rats receiving HCDs showed higher calorie consumption than other groups, (p < 0.01). HRSD showed the lowest levels of serum and hepatic lipids. The HUFD induced the lowest fasting glycemia levels and HOMA-IR values. The HDSD group exhibited the highest insulin resistance and hepatic cholesterol content. In conclusion, HUFD exhibited the most beneficial effects on glycemic control meanwhile HRSD induced the highest reduction on lipid content and did not modify insulin sensitivity. In both groups, HFDs and HCDs, the diet constituents were more important factors than caloric intake for metabolic disturbance and insulin resistance.

Proglumide enhances the antinociceptive effect of cyclooxygenase inhibitors in diabetic rats in the formalin test.

The purpose of this study was to assess the effect of the non-selective cholecystokinin receptor antagonist proglumide on the antinociceptive activity of ketorolac and meloxicam in non-diabetic and diabetic rats. Streptozotocin (60 mg/kg) injection caused hyperglycemia which was maintained for 2 weeks. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Local peripheral ipsilateral, but not contralateral, administration of ketorolac and meloxicam produced antinociception in non-diabetic and diabetic rats. However, the antinociceptive effect of both drugs was significantly reduced in diabetic animals. Proglumide was ineffective by itself and it did not affect the antinociception induced by the cyclooxygenase inhibitors in non-diabetic rats. Contrariwise, proglumide reduced formalin-induced nociception and it increased ketorolac- or meloxicam-induced antinociception in diabetic rats. These results suggest that peripheral cholecystokinin plays an important role in diabetes-induced sensitization as well as in the reduction of the antinociceptive effects of ketorolac and meloxicam in diabetic rats. The combination of cholecystokinin receptor antagonists and ketorolac or meloxicam may be a useful strategy to reduce nociception in diabetic patients.