curcumin and Elephantiasis--Filarial

The aim of this study is to evaluate the antifilarial, antiwolbachial and DNA topoisomerase II inhibitory activity of nanocurcumin (nano-CUR).. Nano-CUR formulations (F1-F6) were prepared using free radical polymerization and were characterized by particle size, morphology, encapsulation efficiency and in vitro release kinetics. Antifilarial potential was evaluated in vivo against Brugian filariasis in an experimental rodent model, Mastomys coucha, by selecting the formulation that maximized parasite elimination characteristics. Wolbachial status was determined by PCR and a relaxation assay was used to estimate DNA topoisomerase II inhibitory activity.. Nano-CUR (F3) having a 60 nm diameter and 89.78% entrapment efficiency showed the most favorable characteristics for the elimination of filarial parasites. In vivo pharmacokinetic and organ distribution studies demonstrate significantly greater C(max) (86.6 ± 2.56 ng ml(-1)), AUC0-∞ (796 ± 89.8 ng d ml(-1)), MRT (19.5 ± 7.82 days) and bioavailability of CUR (70.02%) in the organs from which the adult parasites were recovered. The optimized nano-CUR (F3) (5 × 5 mg/kg, orally) significantly augmented the microfilariciadal and adulticidal action of CUR over free CUR (5 × 50 mg/kg, orally) or Diethylcarbamizine (50 mg/kg, orally) against the Brugia malayi Mastomys coucha rodent model. The PCR results showed complete elimination of wolbachia from the recovered female parasites. Interestingly, nano-CUR was also found to be a novel inhibitor of filarial worm DNA topoisomerase II, Setaria Cervi in vitro.. This study recognizes the beforehand antimicrofilarial, antimacrofilarial, anti-wolbachial activity of nano-CUR (F3) over free forms and additionally its strong inhibitory action against the major target filarial parasite enzyme DNA topoisomerase II in vitro.

Topics: Animals; Brugia; Curcumin; Disease Models, Animal; Drug Carriers; Drug Liberation; Elephantiasis, Filarial; Filaricides; Host-Parasite Interactions; Male; Mice; Nanoparticles; Particle Size; Rats; Surface Properties; Tissue Distribution; Topoisomerase II Inhibitors

Diethylcarbamazine citrate (DEC) is widely used to treat lymphatic filariasis and Tropical Pulmonary Eosinophilia. A number of studies have reported a possible role in the host immune system, but exactly how DEC exerts this effect is still unknown. The present study reports the effects of DEC pretreatment on NF-κB regulation using the pleurisy model induced by carrageenan. Swiss male mice (Mus musculus) were divided into four experimental groups: control (SAL); carrageenan (CAR); diethylcarbamazine (DEC) and curcumin (CUR). The animals were pretreated with DEC (50mg/kg, v.o), CUR (50mg/kg, i.p) or distilled water for three consecutive days before pleurisy. One way analysis of variance (ANOVA) was performed by Tukey post-hoc test, and values were considered statistically significant when p<0.05. DEC pretreatment reduced tissue damage and the production of inflammatory markers, such as NO, iNOS, PGE2, COX-2, and PARP induced by carrageenan. Similarly, a known inhibitor of NF-κB pathway (curcumin) was also able to reduce these parameters. Like curcumin, DEC prevents NF-κB activation by reducing NF-κB p65 phosphorylation and IκBα degradation. DEC prevented NF-κB activation via p38 MAPK, but did not interfere in the ERK pathway in this experimental model. However, further studies should be developed to confirm this hypothesis. These findings suggest that DEC could be a promising drug for inflammatory disorders, especially in pulmonary diseases such as Acute Lung Inflammation, due its high anti-inflammatory potential which prevents NF-κB activation.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Curcumin; Diethylcarbamazine; Disease Models, Animal; Elephantiasis, Filarial; Humans; Inflammation Mediators; Male; Mice; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Pleurisy; Pulmonary Eosinophilia; Signal Transduction; Transcriptional Activation