In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts.

In the context of the cancer-inflammation relationship and the use of natural products as potential antitumor and anti-inflammatory agents, the alkaloid-enriched fraction of Boehmeriacaudata (BcAEF) aerial parts was evaluated. In vitro antiproliferative studies with human tumor cell lines showed high activity at low concentrations. Further investigation on NCI-H460 cells showed an irreversible effect on cell proliferation, with cell cycle arrest at G2/M phase and programmed cell death induction. Molecular docking studies of four alkaloids identified in BcAEF with colchicine's binding site on ß-tubulin were performed, suggesting (-)-C (15R)-hydroxycryptopleurine as the main inductor of the observed mitotic death. In vivo studies showed that BcAEF was able to reduce Ehrlich tumor volume progression by 30 to 40%. Checking myeloperoxidase activity, BcAEF reduced neutrophils migration towards the tumor. The in vivo anti-inflammatory activity was evaluated by chemically induced edema models. In croton oil-induced ear edema and carrageenan (CG)-induced paw edema models, BcAEF reduced edema around 70 to 80% together with inhibition of activation and/or migration of neutrophils to the inflammatory area. All together the results presented herein show BcAEF as a potent antitumor agent combining antiproliferative and anti-inflammatory properties, which could be further explored in (pre)clinical studies.

Artemisia annua L.: evidence of sesquiterpene lactones' fraction antinociceptive activity.

BACKGROUND: Artemisia annua L. has been used for many centuries in Chinese traditional medicine. Artemisinin, the active principle was first isolated and identified in the 1970s becoming the global back bone to the fight against malaria. Our research group previously developed an economic and ecological friendly process to obtain this compound. In the pursuit to also exploit the residue generated throughout the process we further evaluated the pharmacological potential of that extract. METHODS: The alcoholic crude extract after artemisinin precipitation maintained an enriched sesquiterpene lactones content with residue artemisinin (1.72%) and deoxyartemisinin (0.31%), used as chemical markers for this sample. This study evaluated the pharmacological potential of the enriched sesquiterpene lactone fraction (Lac-FR) on different nociceptive and inflammatory experimental animal models. Previous findings on the biological properties of lactones obtained from natural products permitted us to explore the antinociceptive activities of these compounds based on in vivo chemical-induced behavioral assays. RESULTS: The enriched sesquiterpene lactone fraction (Lac-FR) was administrated by intraperitoneal injection producing a relevant reduction in the reaction time of the animals in both phases of the formalin test, significantly reduced the sensitivity to mechanical allodynia stimulus, reduced the paw edema caused by carrageenan injection and promoted high antinociceptive activity in tail flick model suggesting relationship with the opioid system. Further studies are being undertaken to elucidate the active components involved with the antinociceptive activity as well as evaluation of synergy effect that is seen by combination of substances that is greater than would be expected from consideration of individual contributions. CONCLUSION: For the first time, results presented herein provided consistent data to support the potential use of these lactones for pain relief as revealed by chemical-induced nociception assays in mice.

Antiparasitic activities of novel ruthenium/lapachol complexes.

The present study describes the synthesis, characterization, antileishmanial and antiplasmodial activities of novel diimine/(2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 4,4'-methylbipyridine (Me-bipy) and 4,4'-methoxybipyridine (MeO-bipy)/phosphine/ruthenium(II) complexes containing lapachol (Lap, 2-hydroxy-3-(3-33 methyl-2-buthenyl)-1,4-naphthoquinone) as bidentate ligand. The [Ru(Lap)(PPh3)2(bipy)]PF6 (1), [Ru(Lap)(PPh3)2(Me-bipy)]PF6 (2), [Ru(Lap)(PPh3)2(MeO-bipy)]PF6(3) and[Ru(Lap)(PPh3)2(phen)]PF6 (4) complexes, PPh3=triphenylphospine, were synthesized from the reactions of cis-[RuCl2(PPh3)2(X-bipy)] or cis-[RuCl2(PPh3)2(phen)], with lapachol. The [RuCl2(Lap)(dppb)] (5) [dppb=1,4-bis(diphenylphosphine)butane] was synthesized from the mer-[RuCl3(dppb)(H2O)] complex. The complexes were characterized by elemental analysis, molar conductivity, infrared and UV-vis spectroscopy, (31)P{(1)H} and (1)H NMR, and cyclic voltammetry. The Ru(III) complex, [RuCl2(Lap)(dppb)], was also characterized by the EPR technique. The structure of the complexes [Ru(Lap)(PPh3)2(bipy)]PF6 and [RuCl2(Lap)(dppb)] was elucidated by X-ray diffraction. The evaluation of the antiparasitic activities of the complexes against Leishmania amazonensis and Plasmodium falciparum demonstrated that lapachol-ruthenium complexes are more potent than the free lapachol. The [RuCl2(Lap)(dppb)] complex is the most potent and selective antiparasitic compound among the five new ruthenium complexes studied in this work, exhibiting an activity comparable to the reference drugs.