Anti-SARS-CoV-2 Activity of Ampelozizyphus amazonicus (Saracura-Mirá): Focus on the Modulation of the Spike-ACE2 Interaction by Chemically Characterized Bark Extracts by LC-DAD-APCI-MS/MS.

Traditional medicine shows several treatment protocols for COVID-19 based on natural products, revealing its potential as a possible source of anti-SARS-CoV-2 agents. Ampelozizyphus amazonicus is popularly used in the Brazilian Amazon as a fortifier and tonic, and recently, it has been reported to relieve COVID-19 symptoms. This work aimed to investigate the antiviral potential of A. amazonicus, focusing on the inhibition of spike and ACE2 receptor interaction, a key step in successful infection. Although saponins are the major compounds of this plant and often reported as its active principles, a polyphenol-rich extract was the best inhibitor of the spike and ACE2 interaction. Chemical characterization of A. amazonicus bark extracts by LC-DAD-APCI-MS/MS before and after clean-up steps for polyphenol removal showed that the latter play an essential role in maintaining this activity. The effects of the extracts on viral replication were also assessed, and all samples (aqueous and ethanol extracts) demonstrated in vitro activity, inhibiting viral titers in the supernatant of Calu-3 cells after 24 hpi. By acting both in the SARS-CoV-2 cell entry process and its replication, A. amazonicus bark extracts stand out as a multitarget agent, highlighting the species as a promising candidate in the development of anti-SARS-CoV-2 drugs.

7-Ketocholesterol and cholestane-triol increase expression of SMO and LXRα signaling pathways in a human breast cancer cell line.

Oxysterols are 27-carbon oxidation products of cholesterol metabolism. Oxysterols possess several biological actions, including the promotion of cell death. Here, we examined the ability of 7-ketocholesterol (7-KC), cholestane-3ß-5α-6ß-triol (triol), and a mixture of 5α-cholestane-3ß,6ß-diol and 5α-cholestane-3ß,6α-diol (diol) to promote cell death in a human breast cancer cell line (MDA-MB-231). We determined cell viability, after 24-h incubation with oxysterols. These oxysterols promoted apoptosis. At least part of the observed effects promoted by 7-KC and triol arose from an increase in the expression of the sonic hedgehog pathway mediator, smoothened. However, this increased expression was apparently independent of sonic hedgehog expression, which did not change. Moreover, these oxysterols led to increased expression of LXRα, which is involved in cellular cholesterol efflux, and the ATP-binding cassette transporters, ABCA1 and ABCG1. Diols did not affect these pathways. These results suggested that the sonic hedgehog and LXRα pathways might be involved in the apoptotic process promoted by 7-KC and triol.

The influence of changes in lifestyle and mercury exposure in riverine populations of the Madeira River (Amazon Basin) near a hydroelectric project.

In the Amazon Basin, naturally occurring methylmercury bioaccumulates in fish, which is a key source of protein consumed by riverine populations. The hydroelectric power-plant project at Santo Antônio Falls allows us to compare the Hg exposure of riverine populations sparsely distributed on both sides of the Madeira river before the area is to be flooded. From 2009 to 2011, we concluded a population survey of the area (N = 2,008; representing circa 80% of community residents) that estimated fish consumption and mercury exposure of riverine populations with different degrees of lifestyle related to fish consumption. Fish samples from the Madeira river (N = 1,615) and 110 species were analyzed for Hg. Hair-Hg was significantly lower (p < 0.001) in less isolated communities near to the capital of Porto Velho (median 2.32 ppm) than in subsistence communities in the Cuniã Lake, 180 km from Porto Velho city (median 6.3 ppm). Fish Hg concentrations ranged from 0.01 to 6.06 µg/g, depending on fish size and feeding behavior. Currently available fish in the Madeira river show a wide variability in Hg concentrations. Despite cultural similarities, riparians showed hair-Hg distribution patterns that reflect changes in fish-eating habits driven by subsistence characteristics.