Interaction of dicentrinone, an antitrypanosomal aporphine alkaloid isolated from Ocotea puberula (Lauraceae), in cell membrane models at the air-water interface.

In the present work, the oxoaporphine alkaloid dicentrinone was isolated, for the first time, from leaves of Ocotea puberula (Lauraceae). This alkaloid exhibited antiparasitic activity against trypomastigote forms of Trypanosoma cruzi (IC50 of 16.4 ± 1.7 µM), similar to the positive control benznidazole (IC50 of 18.7 ± 4.1 µM), reduced mammalian cytotoxicity (CC50 > 200 µM), and a selectivity index (SI) higher than 12. These results were correlated with the effects observed using cellular membrane models, represented by 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), in Langmuir monolayers. Dicentrinone was incorporated in the films, submitted to lateral compression, and characterized by tensiometry. As observed in compression-decompression and time-stability curves, dicentrinone expanded the lipid monolayers, decreased the compressional modulus of the film, and reduced the stability of the monolayer. Brewster Angle Microscopy and interfacial Infrared Spectroscopy showed that dicentrinone causes the monolayers to be segregated in phases, and to increase the number of gauche/trans conformers ratio for the lipid acyl methylene groups, indicating configurational disorder. As a result, dicentrinone caused a disturbance in the cell membrane models, altering the physicochemical properties of the lipid surface such as thermodynamic, rheological, morphological, and structural aspects. These results can be useful to understand the interactions between dicentrinone and lipid biological surfaces at the molecular level.

Antioxidant, anti-rheumatic and anti-inflammatory investigation of extract and dicentrinone from Duguetia furfuracea (A. St.-Hil.) Benth. & Hook. f.

ETHNOPHARMACOLOGICAL RELEVANCE: The preparations of teas and syrups using Duguetia furfuracea have been used in folk medicine to treat rheumatism and back pain. Several rheumatic diseases are anti-inflammatory and are treated with several anti-inflammatories. AIM OF THE STUDY: The objective of this work were to evaluate the chemical investigation of methanolic extract obtained from leaves of D. furfuracea (MEDF) and test the MEDF, such as chloroform (CF), ethyl acetate (EAF) and hydromethanol (HMF) fractions and the alkaloid dicentrinone (DF-1) in vitro antioxidant effects and in vivo models of inflammation. MATERIAL AND METHODS: MEDF and CF were analyzed by LC-PDA and the results revealed the presence of alkaloid aporphine and oxoaporphine. The concentrations of total phenols, flavonoids and flavonols were determined. Additionally, MEDF, fractions and dicentrinone were evaluated free radical scavenging activity 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and peroxidation ß-carotene/linoleic acid and malondialdehyde (MDA) assays. The anti-inflammatory effects of MEDF, fractions and dicentrinone were studied in carrageenan-induced paw edema. The anti-rheumatic potential was studied in air pouch model and zymosan-induced arthritis. RESULTS: CF fractionation resulted in the isolation of the oxaporphine alkaloid dicentrinone (DF-1). The highest phenols (624.37mg GAE/g extract), flavonoids (580.51mg QE/g extract) and flavonols (254.44mg QE/g extract), concentration was found in extract. In antioxidant tests, MEDF exhibited the highest scavenging activity and lipoperoxidation. The extract (30-300mg/kg) and all tested fractions inhibited the edema induced by carrageenan. The oral administration of DF-1 inhibited both edema associated with carrageenan-induced inflammation in mice. In air pouch model of inflammation, MEDF (30-300mg/kg) and DF-1 (100mg/kg) inhibited leukocyte migration and plasmatic leakage induced by carrageenan in mice. Finally, MEDF (100mg/kg) did not alter zymozan-induced arthritis in mice. CONCLUSION: The results showed that D. furfuracea exhibits antioxidant, anti-rheumatic potential and anti-inflammatory activity. The presence of the alkaloid dicentrinone in extract and CF fraction could be responsible, at least in part, for the observed effects.