Structural characterization of a proanthocyanidin-rich fraction from Hancornia speciosa leaves and its effect on the release of pro-inflammatory cytokines and oxidative stress in THP-1 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, the leaves of Hancornia speciosa Gomes have a traditional use for treating hypertension and diabetes. Experimental investigations have confirmed the anti-hypertensive and hypoglycemic properties of extracts derived from H. speciosa leaves across various experimental models. These biological activities have been mostly ascribed to its major constituent, bornesitol, along with other cyclitols, flavonoids, and cinnamic acid derivatives. AIM OF STUDY: The objective of this study was to characterize the chemical structure of proanthocyanidins from H. speciosa leaves and explore their in vitro activity on the release of pro-inflammatory cytokines and oxidative stress. MATERIAL AND METHODS: The acetone/water (7:3) extract of H. speciosa leaves (HsE) was prepared by percolation and fractionated by column chromatography over Sephadex LH20 to afford the proanthocyanidin-rich fraction HsFr3. Structure characterization of the proanthocyanidins constituents of HsFr3 was accomplished by extensive UPLC-DAD-ESI-MS/MS analysis coupled to degradation reaction through thiolysis. The effect of HsE, HsFr3, and bornesitol on the release of TNF, IL-1ß and IL-6 in LPS-stimulated THP-1 cells was assayed by ELISA. The effect of the samples on oxidative stress induced by LPS in THP-1 cell was investigated using a DCFH-DA fluorescent assay. RESULTS: Fractionation of HsE afforded HsFr3, primarily composed of six proanthocyanidins. Their chemical structures were characterized as dimeric (4 isomers) and trimeric (2 isomers) procyanidins C-glycosides of the B-type. HsE, HsFr3, and bornesitol reduced the release of pro-inflammatory cytokines TNF and IL-1ß in LPS-stimulated THP-1 cells, while no significant effect was observed on IL-6. All samples reduced the oxidative stress induced by LPS in THP-1 cells, whereas bornesitol, tested at lower concentrations, induced an equivalent response to HsE and HsFr3. CONCLUSIONS: Our findings provide additional evidence to support the ethnomedical use of H. speciosa in managing hypertension and hyperglycemia, due to the direct association of oxidative stress, TNF, and IL-1ß with the maintenance and aggravation of these deleterious conditions. The dimeric and trimeric procyanidin C-glycosides, characterized in the species, contribute to diminish oxidative stress and the release or pro-inflammatory cytokines, whereas bornesitol was shown to induce similar effect at lower concentrations.

Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review.

Zika virus (ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants (82.4%) or semisynthetic/synthetic derivatives, fungi (3.1%), bacteria (7.6%), animals (1.2%) and marine organisms (1.9%) along with miscellaneous compounds (3.8%). Classes of NPs reported to present anti-ZIKV activity include polyphenols, triterpenes, alkaloids, and steroids, among others. The highest values of the selectivity index, the ratio between cytotoxicity and antiviral activity (SI = CC50/EC50), were reported for epigallocatechin gallate (SI ≥ 25,000) and anisomycin (SI ≥ 11,900) obtained from Streptomyces bacteria, dolastane (SI = 1246) isolated from the marine seaweed Canistrocarpus cervicorni, and the flavonol myricetin (SI ≥ 862). NPs mostly act at the stages of viral adsorption and internalization in addition to presenting virucidal effect. The data demonstrate the potential of NPs for developing new anti-ZIKV agents and highlight the lack of studies addressing their molecular mechanisms of action and pre-clinical studies of efficacy and safety in animal models. To the best of our knowledge, none of the active compounds has been submitted to clinical studies.

Rate of exposure to Mayaro virus (MAYV) in Brazil between 1955 and 2018: a systematic review and meta-analysis.

Mayaro fever is an infection caused by Mayaro virus (MAYV) that stands out among the neglected diseases transmitted by arthropods. Brazil is the country with the highest number of confirmed cases of MAYV infection. However, epidemiological surveillance studies conducted in Brazil are decentralized and focus on small outbreaks and unconfirmed cases. Thus, the aim of this review was to determine the general epidemiological profile of MAYV infections in Brazil. Several medical databases (i.e., PUBMED/MEDLINE, Scopus, Cochrane Library, LILACS, SciELO, and Biblioteca Virtual em Saúde) were searched for studies reporting cases of MAYV infections in Brazilian patients. Then, the rate of exposure to MAYV in Brazil was analyzed using RStudio® Software. We identified 37 studies published from 1957 to 2019, containing data of 12,374 patients from 1955 to 2018. The general rate of exposure to MAYV in Brazil was 10% (95% CI; 0.04-0.22), with 1,304 reported cases. The highest incidence of MAYV infection was found in the northern region (13%; 95% CI; 0.05-0.29), with 1,142 cases (88% of all cases). Furthermore, autochthonous MAYV cases have also been reported in the Central West (8%; 95% CI; 0.03-0.18) and Southeast (0.4%; 95% CI; 0.00-0.28). The states with the highest number of cases are Amazonas (490 cases), Pará (276 cases), and Goiás (87 cases). In conclusion, the general rate of exposure to MAYV in Brazil between 1955 and 2018 was considerable, especially in the Legal Amazon, in which 93% of cases were reported.