Anti-inflammatory Effect and Toxicology Analysis of Oral Delivery Quercetin Nanosized Emulsion in Rats.

PURPOSE: This study evaluates the advantage of the quercetin encapsulation in nanosized emulsion (QU-NE) administered orally in rats in order to demonstrate its anti-oedematous and antioxidant effects as well as its toxicity. METHODS: The nanocarriers were prepared using the hot solvent diffusion with the phase inversion temperature methods. The nanocarriers physicochemical properties were then investigated. The anti-edematous activity was tested using paw edema in rats. In addition, NF-kB expression in subcutaneous tissue of the paws was accessed by immunohistochemistry while the lipid peroxidation was analyzed in the liver by malondialdehyde reaction with thiobarbituric acid. Hematological, renal and hepatic toxicity as well as the genetic damage were also evaluated. RESULTS: The results demonstrated that QU-NE exhibited pronounced anti-oedematous property comparable to drug diclofenac. This effect was associated with NF-κB pathway inhibition. The lipid peroxidation was also only reduced in rats treated with QU-NE. Besides this, no genetic damage, hematological, renal or hepatic toxicities were observed after administration of QU-NE. CONCLUSIONS: These results suggest that quercetin nanosized emulsion exhibits anti-oedematous and antioxidant properties and does not demonstrate toxic effects. This indicates that it has a potential application in the treatment of inflammatory diseases.

Interactions between anandamide-induced anterograde amnesia and post-training memory modulatory systems.

Rats were bilaterally implanted with indwelling cannulae in the CA1 region of the dorsal hippocampus. After recovery from surgery, they were trained in a one-trial, step-down inhibitory avoidance task using a 0.5 mA foot shock. The animals received intrahippocampal infusions of either vehicle or anandamide (100 microM, 0.5 microl/side) 30 min before training. Then, either immediately post-training or 3 h later, they received infusions of saline, noradrenaline (0.5 microg/side), SKF 38393 (1.5 microg/side), oxotremorine (0.6 microg/side) or Sp-cAMPs (0.5 microg/side) also in the hippocampus. All animals were tested for retention 24-h post-training. Anandamide produced anterograde amnesia. Immediate, but not delayed, post-training treatment with Sp-cAMPs and noradrenaline reversed this effect. SKF 38393 and oxotremorine had no influence on the amnesia caused by anandamide either when given immediately or 3 h after training. The results suggest that the amnesic effect of anandamide is related to the known noradrenergic regulation of cAMP-dependent protein kinase (PKA) activity previously described in the hippocampus immediately after avoidance training, which is crucial to long-term memory (LTM) formation.