New flavone, and cytotoxicity activity of Rauia resinosa ethanolic extract and constituents.

The ethanolic extract from leaves of Rauia resinosa, Rutaceae, provided a new flavone, 5-hydroxy-5',6,7-trimethoxy-3',4'-methylenedioxyflavone (1), in addition to four known compounds: 3',4',5,5',7-pentamethoxyflavone (2), 5,7,8-trimethoxy-3'4'-methylenedioxyflavone (3), 3',4',5,7,8-pentamethoxyflavone (4) and ß-sitosterol (5). The structures of all compounds were established on the basis of spectroscopic methods, mainly 1D and 2D NMR, UPLC-DAD-MS and UPLC-ESI-MS/MS, involving comparison with literature data. Cytotoxicity of leaves and stems extracts, their fractions and compounds (2), (3), (4) and (5) were evaluated against T24 (bladder carcinoma), TOV-21-G (ovarian adenocarcinoma) and HepG2 (liver carcinoma) cell lines.

Anti-arboviral activity and chemical characterization of hispidulin and ethanolic extracts from Millingtonia hortensis L.f. and Oroxylum indicum (L.) Kurz (Bignoniaceae).

Millingtonia hortensis L.f. and Oroxylum indicum (L.) Kurz (Bignoniaceae) are native species from the Asian continent. They are popularly used in traditional medicine and their extracts are rich in flavonoids. In this work, ethanolic extracts of stems and leaves of these species were evaluated against the Chikungunya, Zika and Mayaro virus. The extracts were subjected to analysis by ultra-efficient liquid chromatography coupled to mass spectrometry. Additionally, M. hortensis leaves extract was fractionated, leading to the isolation of hispidulin. Anti-arboviral activity against the three viruses was detected for M. hortensis leaves extract with EC50 ranging from 37.8 to 134.1 µg/mL and for O. indicum stems extract with EC50 ranging from 18.6 to 55.9 µg/mL. Hispidulin inhibited viral cytopathic effect of MAYV (EC50 value 32.2 µM) and CHIKV (EC50 value 78.8 µM). In LC-DAD-ESI-MS/MS analysis we characterized 25 flavonoids confirming once again the presence of these substances in extracts of these species.

Antiviral effect of silymarin against Zika virus in vitro.

Zika virus (ZIKV) epidemic and its association with severe neurological syndromes have raised worldwide concern. Despite the great clinical relevance of this infection, no vaccine or specific treatment is available and the search for antiviral compounds against ZIKV is extremely necessary. Several natural compounds, such as silymarin, exhibit antioxidant, hepatoprotective, and antiviral properties; however, the antiviral potential of this compound remains partially investigated. Therefore, the objective of this study was to evaluate in vitro the antiviral activity of silymarin against ZIKV infection. Global antiviral activity, dose-dependent, plaque reduction, and time-of-drug-addition assays were used to determine the anti-ZIKV activity of silymarin. Additionally, to start characterizing the mechanisms of action we determined whether silymarin could have a virucidal effect and inhibit viral adsorption and penetration stages. Regarding its global antiviral activity, silymarin showed significant inhibition of ZIKV infection, protecting cells infected with EC50 equal to 34.17µg/mL, with a selectivity index greater than 17 and 4x greater than that of the positive control (ribavirin). Its greatest efficiency was achieved at 125µg/mL, whose cell viability did not differ from the control without infection and treatment. Furthermore, treatment with silymarin reduced viral load by up to two logs (> 90%) concerning viral control, when evaluating virucidal activity and the precocious times of infection. Thus, our results set to show the promising anti-ZIKV activity of silymarin, which does not seem to have a single inhibition mechanism, acting at different times of infection, and still has the advantage of silymarin be a phytotherapy already available on the market.