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Despite substantial morbidity and mortality, no therapeutic agents exist for treatment of dengue or Zika, and the currently available dengue vaccine is only recommended for dengue virus (DENV)-immune individuals. Thus, development of therapeutic and/or preventive drugs is urgently needed. DENV and Zika virus (ZIKV) nonstructural protein 1 (NS1) can directly trigger endothelial barrier dysfunction and induce inflammatory responses, contributing to vascular leak in vivo. Here we evaluated the efficacy of the (1-6,1-3)-β-D-glucan isolated from Agaricus subrufescens fruiting bodies (FR) and its sulfated derivative (FR-S) against DENV-2 and ZIKV infection and NS1-mediated pathogenesis. FR-S, but not FR, significantly inhibited DENV-2 and ZIKV replication in human monocytic cells (EC

Agaricus brasiliensis cell-wall polysaccharides isolated from fruiting body (FR) and mycelium (MI) and their respective sulfated derivatives (FR-S and MI-S) were chemically characterized using elemental analysis, TLC, FT-IR, NMR, HPLC, and thermal analysis. Cytotoxic activity was evaluated against A549 tumor cells by MTT and sulforhodamine assays. The average molecular weight (Mw) of FR and MI was estimated to be 609 and 310 kDa, respectively. FR-S (127 kDa) and MI-S (86 kDa) had lower Mw, probably due to hydrolysis occurring during the sulfation reaction. FR-S and MI-S presented ~14% sulfur content in elemental analysis. Sulfation of samples was characterized by the appearance of two new absorption bands at 1253 and 810 cm(-1) in the infrared spectra, related to S=O and C-S-O sulfate groups, respectively. Through (1)H and (13)C NMR analysis FR-S was characterized as a (1→6)-(1→3)-β-D-glucan fully sulfated at C-4 and C-6 terminal and partially sulfated at C-6 of (1→3)-β-D-glucan moiety. MI-S was shown to be a (1→3)-β-D-gluco-(1→2)-β-D-mannan, partially sulfated at C-2, C-3, C-4, and C-6, and fully sulfated at C-6 of the terminal residues. The combination of high degree of sulfation and low molecular weight was correlated with the increased cytotoxic activity (48 h of treatment) of both FR-S (EC₅₀=605.6 μg/mL) and MI-S (EC₅₀=342.1 μg/mL) compared to the non-sulfated polysaccharides FR and MI (EC₅₀>1500 μg/mL).

Ethnopharmacological relevance: Araucaria angustifolia (Bert.) O. Kuntze (Araucariaceae) is a Brazilian medicinal plant traditionally used for the treatment of various illnesses including dried skin, wounds, shingles, and sexually transmitted diseases. Aim of the study: The rationale of the study was to provide evidence of its antiherpes activity in order to confirm its popular use that could be related to herpes disease. Materials and methods: The crude hydroethanolic extract (HE) obtained from Araucaria angustifolia leaves was submitted to a sequential liquid–liquid extraction with solvents of increased polarity. The HE and fractions obtained were evaluated for cytotoxicity and antiherpes activity (Herpes Simplex Virus type 1) by MTT assay. The most active fractions were selected to perform an in vitro antiviral activity-guided chromatographic fractionation. Results: The ethyl acetate (EA) and n-butanol (NB) fractions have shown the best results for antiherpetic activity and their further fractionation yielded 22 subfractions. From these subfractions, 14 were active, and the most potent antiherpetic activity was obtained for NB1-4 subfraction with selectivity index (SI) of 57.51. Chemical analysis of NB1-4 subfractions revealed the presence of proanthocyanidins and the known biflavonoids (bilobetin, II-7-O-methyl-robustaflavone and cupressuflavone). The same biflavonoids have been detected in EA subfractions. Conclusion: The present study has shown that the hydroethanolic extract from Araucaria angustifolia leaves as well as many different fractions and subfractions exhibited antiherpes activity, supporting the use of this plant species in folk medicine.