Anti-Zika Virus Activity of Plant Extracts Containing Polyphenols and Triterpenes on Vero CCL-81 and Human Neuroblastoma SH-SY5Y Cells.

Zika virus (ZIKV) infection is a global threat associated to neurological disorders in adults and microcephaly in children born to infected mothers. No vaccine or drug is available against ZIKV. We herein report the anti-ZIKV activity of 36 plant extracts containing polyphenols and/or triterpenes. ZIKV-infected Vero CCL-81 cells were treated with samples at non-cytotoxic concentrations, determined by MTT and LDH assays. One third of the extracts elicited concentration-dependent anti-ZIKV effect, with viral loads reduction from 0.4 to 3.8 log units. The 12 active extracts were tested on ZIKV-infected SH-SY5Y cells and significant reductions of viral loads (in log units) were induced by Maytenus ilicifolia (4.5 log), Terminalia phaeocarpa (3.7 log), Maytenus rigida (1.7 log) and Echinodorus grandiflorus (1.7 log) extracts. Median cytotoxic concentration (CC50 ) of these extracts in Vero cells were higher than in SH-SY5Y lineage. M. ilicifolia (IC50 =16.8±10.3 µg/mL, SI=3.4) and T. phaeocarpa (IC50 =22.0±6.8 µg/mL, SI=4.8) were the most active extracts. UPLC-ESI-MS/MS analysis of M. ilicifolia extract led to the identification of 7 triterpenes, of which lupeol and a mixture of friedelin/friedelinol showed no activity against ZIKV. The composition of T. phaeocarpa extract comprises phenolic acids, ellagitannins and flavonoids, as recently reported by us. In conclusion, the anti-ZIKV activity of 12 plant extracts is here described for the first time and polyphenols and triterpenes were identified as the probable bioactive constituents of T. phaeocarpa and M. ilicifolia, respectively.

Biological activities of extracts from Aspidosperma subincanum Mart. and in silico prediction for inhibition of acetylcholinesterase.

Species of Aspidosperma are traditionally used to treat malaria, leishmaniasis, microbial, and inflammatory diseases. Aspidosperma subincanum Mart. known as "guatambu" is used in Brazilian traditional medicine to treat diabetes, hypercholesterolemia, and digestive diseases. Its tonic properties have been employed by the indigenous populations to stimulate the circulatory and genitourinary tracts and to improve respiratory function as well as to relieve spasms and to reduce fever. The species is known to contain antitumoural and antimalarial indole alkaloids. In the present study, various less explored biological activities of extracts from leaves and branches of A. subincanum were investigated, that is, inhibition of acetylcholinesterase as well as antioxidant and antibacterial activity. Twenty-one known indole alkaloids from this species were targeted for predicting the inhibition of acetylcholinesterase, and their biological activities were collected from the literature. Through in silico the prediction, the indole alkaloids uleine and derivatives demonstrated a strong probability of being able to inhibit the acetylcholinesterase enzyme, as well as the olivacine derivatives 3,4-dihydroolivacine and N-methyl-tetrahydro-olivacine (guatambuine), and the subincanadines C and E. Indeed, the extracts of A. subincanum showed acetylcholinesterase inhibitory activity, antioxidant activity in the lipid peroxidation assay, and antimicrobial activity against Staphylococcus aureus ATCC 25923, and their pharmacological properties should be explored further.