4-hydroxylonchocarpin and Disease-Models--Animal

Antileishmanial activities of thirty-five synthetic chalcones have been examined. Among them, ten compounds (4, 6, 16, 22, 23, 24, 25, 29, 35 and 37) exhibited potent in vitro activity (IC50 range from 1.70 to 8 μM) against extracellular promastigotes and intracellular amastigotes form of Leishmania donovani. Two promising compounds 22 and 37 were tested in vivo in L. donovani/hamster model. Chalcone 37 showed 83.32% parasite inhibition at a dose of 50 mg/kg for 10 days whereas, 75.89% parasite inhibition at 100 mg/kg dose for 5 days by intraperitoneal route at day 7 post-treatment.

Topics: Animals; Cell Line; Chalcones; Chlorocebus aethiops; Cricetinae; Disease Models, Animal; Dose-Response Relationship, Drug; Injections, Intraperitoneal; Leishmania donovani; Leishmaniasis, Visceral; Macrophages; Mice; Molecular Structure; Parasitic Sensitivity Tests; Structure-Activity Relationship; Trypanocidal Agents; Vero Cells

The present study was designed to investigate the in vitro and in vivo anti-inflammatory activity of flavonoids isolated from Millettia pachycarpa Benth. The seeds of M. pachycarpa Benth were extracted with ethanol and subjected to chromatographic separation for the isolation of bioactive compounds. Their structures were elucidated by spectroscopic methods. The anti-inflammatory activity of the compounds was investigated by evaluating the inhibition ability of NO production, iNOS activity and iNOS protein expression induced by LPS-stimulated RAW264.7 macrophages in vitro and the carrageenan-induced hind paw edema model in vivo. Molecular docking simulation was also employed to obtain the binding parameters in the binding pocket of iNOS. Thirteen compounds (1-13) were isolated from Chinese herbal medicine M. pachycarpa Benth. Among them, 4-hydroxylonchocarpin (6) and deguelin (7) exhibited remarkable inhibitory rates of 66.5% and 57.7%, respectively, compared with that of 52.5% of indomethacin in LPS-induced macrophages cells. 4-hydroxylonchocarpin (6) with low toxicity (IC50 > 100 μm) exhibited better inhibitory effects to positive control of 1400W on iNOS activity at the concentration of 10 μm. Western blot assay revealed that 4-hydroxylonchocarpin (6) inhibited iNOS protein expression in RAW264.7 cells and molecular docking simulation showed that 4-hydroxylonchocarpin (6) fit well into the binding pocket of iNOS. In the carrageenan-induced paw edema model, our data revealed that the anti-inflammatory potential of 4-hydroxylonchocarpin (6) at 10 mg/kg showed comparable inhibitory ability to indomethacin at 5 h while a higher concentration of 4-hydroxylonchocarpin (6) at 50 mg/kg showed higher inhibitory activity than indomethacin, which was further confirmed by plasma levels of nitrite. The overall results suggest that 4-hydroxylonchocarpin (6) might be used as a potential therapeutic agent for inflammation-associated disorders.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Cells, Cultured; Depression, Chemical; Disease Models, Animal; Edema; Flavones; Flavonoids; Lipopolysaccharides; Macrophages; Male; Mice, Inbred ICR; Millettia; Nitric Oxide; Nitric Oxide Synthase Type II; Phytotherapy; Rotenone; Seeds