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Malva sylvestris derivatives as inhibitors of HIV-1 BaL infection.

ABSTRACT: The emphasis of the present study is to evaluate a natural product and the potential microbicide activity using a dual chamber infection method. Malva sylvestris extracts and fractions were screened for anti-HIV activity by measuring the virus-antibody neutralization. Plant extracts with strong antiviral activity working in nanomolar or picomolar range can be used to enhance the activity of synthetic compounds and work as anti-HIV agents. The aqueous fraction (AF) of M. sylvestris demonstrated antiviral activity in a model with epithelial and blood cell lines. The AF showed an effective antiviral potential on the TZM-bl cells with reduction scores higher than 60% of infectivity. Quantification of p24 in the supernatant of the co-culture model demonstrated a reduction in the number of viral particles after AF treatment (p < 0.05). Cytokines were quantified and all signaling inflammatory markers; IL1-alpha, IL-beta, IL-6, IL-8 and GM-CSF (p < 0.05) were modulated by positive control and AF treatments. In particular, IL-6 had lower levels of expression in Malva groups when compared to the Zidovudine positive control group. Natural occurring derivatives of M. sylvestris demonstrated to work inhibiting reverse transcriptase enzyme action. M. sylvestris contains highly potential anti-HIV-1 BaL components and may be considered a potential source for new formulations in the development of topical microbicides.

SUBMITTER: Benso B

PROVIDER: S-EPMC7031020 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The aim of this study was to investigate the in vitro anti-inflammatory activity of Malva sylvestris extract (MSE) and fractions in a co-culture model of cells infected by Aggregatibacter actinomycetemcomitans. In addition, we evaluated the phytochemical content in the extract and fractions of M. sylvestris and demonstrated that polyphenols were the most frequent group in all samples studied. An in vitro dual-chamber model to mimic the periodontal structure was developed using a monolayer of epithelial keratinocytes (OBA-9) and a subepithelial layer of fibroblasts (HGF-1). The invasive periodontopathogen A. actinomycetemcomitans (D7S-1) was applied to migrate through the cell layers and induce the synthesis of immune factors and cytokines in the host cells. In an attempt to analyze the antimicrobial properties of MSE and fractions, a susceptibility test was carried out. The extract (MIC 175 ?g/mL, MBC 500?g/mL) and chloroform fraction (MIC 150 ?g/mL, MBC 250 ?g/mL) were found to have inhibitory activity. The extract and all fractions were assessed using a cytotoxicity test and results showed that concentrations under 100 ?g/mL did not significantly reduce cell viability compared to the control group (p > 0.05, viability > 90%). In order to analyze the inflammatory response, transcriptional factors and cytokines were quantified in the supernatant released from the cells. The chloroform fraction was the most effective in reducing the bacterial colonization (p< 0.05) and controlling inflammatory mediators, and promoted the down-regulation of genes including IL-1beta, IL-6, IL-10, CD14, PTGS, MMP-1 and FOS as well as the reduction of the IL-1beta, IL-6, IL-8 and GM-CSF protein levels (p< 0.05). Malva sylvestris and its chloroform fraction minimized the A. actinomycetemcomitans infection and inflammation processes in oral human cells by a putative pathway that involves important cytokines and receptors. Therefore, this natural product may be considered as a successful dual anti-inflammatory-antimicrobial candidate.

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Malva sylvestris derivatives as inhibitors of HIV-1 BaL infection.

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