curcumin and Filariasis

With the development of resistance to conventionally used synthetic insecticides, vector management has become acutely problematic. Hence more attention has been focused on botanicals. Therefore our present study was aimed to evaluate the efficacy of extracts from rhizomes of Curcuma aromatica against the larvae of filariasis vector mosquitoes, Culex quinquefasciatus employing standard WHO procedure at Mysore. The soxhlet extraction was carried out using non-polar organic solvent, petroleum ether. The efficacy of petroleum ether extract seemed to be effective with LC(50) and LC(90) values of 11.42 and 18.00 ppm respectively. Bioassay-guided fractionation through flash chromatography lead to the isolation of two larvicidal compounds namely 9-oxoneoprocurcumenol and neoprocurcumenol. Between the two, 9-oxoneoprocurcumenol exerted significant toxicity (P<0.01) on mosquito larvae with LC(50) value of 5.81 ppm and LC(90) being 9.99 ppm compared to neoprocurcumenol with 13.69 and 23.92 ppm of LC(50) and LC(90) values respectively. From the results, C. aromatica could be considered as one of the powerful candidate to bring about useful botanicals so as to prevent the resurgence of mosquito vectors.

Topics: Alkanes; Animals; Culex; Curcuma; Drugs, Chinese Herbal; Filariasis; Insect Vectors; Insecticides; Larva; Lethal Dose 50; Mosquito Control; Rhizome; Sesquiterpenes

Female adult bovine filarial worms Setaria digitata were extracted with phosphate-buffered saline (pH 7.4) and glutathione S-transferase (GST) activity and protein content were determined. The protein content, GST enzyme activity, and specific activity were 10.61 +/- 3.41 mg ml(-1), 0.09 +/- 0.019 micromol min(-1) ml(-1), and 0.009 +/- 0.002 micromol min(-1) mg(-1) protein, respectively. The GST inhibition studies were performed with and without the inhibitors resulted from earlier molecular docking studies viz., ethacrynic acid, plumbagin, and curcumin for which the IC(50) values were 19.42, 51.41, and 114.86 microM, respectively. The in vitro macrofilaricidal activity of these molecules was studied by worm motility and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay at 24- and 48-h incubation. Plumbagin and ethacrynic acid showed 100% inhibition in worm motility at lower concentrations of 3.19 and 6.6 microM, respectively, at 48-h incubation while curcumin was effective at 54.29 microM. In MTT reduction assay, the ED(50) values (50% inhibition in formazan formation) for plumbagin, ethacrynic acid, and curcumin at 48-h incubation were 1.20, 2.48, and 19.86 microM, respectively. MTT reduction assay showed that plumbagin was the most effective in killing the adult S. digitata worms followed by ethacrynic acid and curcumin. In conclusion, all the three molecules selected by molecular modeling and docking studies inhibited the GST enzyme isolated from S. digitata and exhibited macrofilaricidal activity in vitro.

Topics: Animals; Cattle; Cattle Diseases; Curcumin; Ethacrynic Acid; Female; Filariasis; Filaricides; Filarioidea; Glutathione Transferase; Helminth Proteins; Inhibitory Concentration 50; Locomotion; Naphthoquinones; Survival Analysis