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Natural Polyphenol-Containing Gels against HSV-1 Infection: A Comparative Study.

ABSTRACT: Herpes simplex virus type 1 infection commonly affects many people, causing perioral sores, as well as severe complications including encephalitis in immunocompromised patients. The main pharmacological approach involves synthetic antiviral drugs, among which acyclovir is the golden standard, often leading to resistant virus strains under long-term use. An alternative approach based on antiviral plant-derived compounds, such as quercetin and mangiferin, demonstrated an antiviral potential. In the present study, semisolid forms for cutaneous application of quercetin and mangiferin were designed and evaluated to treat HSV-1 infection. Phosphatidylcholine- and poloxamer-based gels were produced and characterized. Gel physical-chemical aspects were evaluated by rheological measurements and X-ray diffraction, evidencing the different thermoresponsive behaviors and supramolecular organizations of semisolid forms. Quercetin and mangiferin diffusion kinetics were compared in vitro by a Franz cell system, demonstrating the different gel efficacies to restrain the polyphenol diffusion. The capability of gels to control polyphenol antioxidant potential and stability was evaluated, indicating a higher stability and antioxidant activity in the case of quercetin loaded in poloxamer-based gel. Furthermore, a plaque reduction assay, conducted to compare the virucidal effect of quercetin and mangiferin loaded in gels against the HSV-1 KOS strain, demonstrated the suitability of poloxamer-based gel to prolong the polyphenol activity.

SUBMITTER: Sicurella M

PROVIDER: S-EPMC8780422 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX® B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX® B/E vaccine contains two gp120 envelope glycoproteins, one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244 isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV-1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV-2 gD sequence. We assessed whether vaccine-induced anti-gD antibodies protected females against HSV-2 acquisition in RV144.MethodsOf the women enrolled in RV144, 777 vaccine and 807 placebo recipients were eligible and randomly selected according to their pre-vaccination HSV-1 and HSV-2 serostatus for analysis. Immunoglobulin G (IgG) and IgA responses to gD were determined by a binding antibody multiplex assay and HSV-2 serostatus was determined by Western blot analysis. Ninety-three percent and 75% of the vaccine recipients had anti-gD IgG and IgA responses two weeks post last vaccination, respectively. There was no evidence of reduction in HSV-2 infection by vaccination compared to placebo recipients over 78 weeks of follow-up. The annual incidence of HSV-2 infection in individuals who were HSV-2 negative at baseline or HSV-1 positive and HSV-2 indeterminate at baseline were 4.38/100 person-years (py) and 3.28/100 py in the vaccine and placebo groups, respectively. Baseline HSV-1 status did not affect subsequent HSV-2 acquisition. Specifically, the estimated odds ratio of HSV-2 infection by Week 78 for female placebo recipients who were baseline HSV-1 positive (n = 422) vs. negative (n = 1120) was 1.14 [95% confidence interval 0.66 to 1.94, p = 0.64)]. No evidence of reduction in the incidence of HSV-2 infection by vaccination was detected.ConclusionsAIDSVAX® B/E containing gD did not confer protection from HSV-2 acquisition in HSV-2 seronegative women, despite eliciting anti-gD serum antibodies.

Project description:Transcriptome analysis is a powerful tool that enables a deep understanding of complicated physiological pathways, including immune responses. RNA sequencing (RNA-Seq)-based transcriptome analysis and various bioinformatics tools have also been used to study non-model animals, including aquaculture species for which reference genomes are not available. Rapid developments in these techniques have not only accelerated investigations into the process of pathogenic infection and defense strategies in fish, but also used to identify immunity-related genes in fish. These findings will contribute to fish immunotherapy for the prevention and treatment of bacterial infections through the design of more specific and effective immune stimulants, adjuvants, and vaccines. Until now, there has been little information regarding the universality and diversity of immune reactions against pathogenic infection in fish. Therefore, one of the aims of this paper is to introduce the RNA-Seq technique for examination of immune responses in pathogen-infected fish. This review also aims to highlight comparative studies of immune responses against bacteria, based on our previous findings in largemouth bass (Micropterus salmoides) against Nocardia seriolae, gray mullet (Mugil cephalus) against Lactococcus garvieae, orange-spotted grouper (Epinephelus coioides) against Vibrio harveyi, and koi carp (Cyprinus carpio) against Aeromonas sobria, using RNA-seq techniques. We demonstrated that only 39 differentially expressed genes (DEGs) were present in all species. However, the number of specific DEGs in each species was relatively higher than that of common DEGs; 493 DEGs in largemouth bass against N. seriolae, 819 DEGs in mullets against L. garvieae, 909 in groupers against V. harveyi, and 1471 in carps against A. sobria. The DEGs in different fish species were also representative of specific immune-related pathways. The results of this study will enhance our understanding of the immune responses of fish, and will aid in the development of effective vaccines, therapies, and disease-resistant strains.

Project description:Antimicrobial resistance has attracted worldwide attention and remains an urgent issue to resolve. Discovery of novel compounds is regarded as one way to circumvent the development of resistance and increase the available treatment options. Gossypol is a natural polyphenolic aldehyde, and it has attracted increasing attention as a possible antibacterial drug. In this paper, we studied the antimicrobial properties (minimum inhibitory concentrations) of gossypol acetate against both Gram-positive and Gram-negative bacteria strains and dig up targets of gossypol acetate using in vitro assays, including studying its effects on functions (GTPase activity and polymerization) of Filamenting temperature sensitive mutant Z (FtsZ) and its interactions with FtsZ using isothermal titration calorimetry (ITC), and in vivo assays, including visualization of cell morphologies and proteins localizations using a microscope. Lastly, Bacterial membrane permeability changes were studied, and the cytotoxicity of gossypol acetate was determined. We also estimated the interactions of gossypol acetate with the promising target. We found that gossypol acetate can inhibit the growth of Gram-positive bacteria such as the model organism Bacillus subtilis and the pathogen Staphylococcus aureus [both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA)]. In addition, gossypol acetate can also inhibit the growth of Gram-negative bacteria when the outer membrane is permeabilized by Polymyxin B nonapeptide (PMBN). Using a cell biological approach, we show that gossypol acetate affects cell division in bacteria by interfering with the assembly of the cell division FtsZ ring. Biochemical analysis shows that the GTPase activity of FtsZ was inhibited and polymerization of FtsZ was enhanced in vitro, consistent with the block to cell division in the bacteria tested. The binding mode of gossypol acetate in FtsZ was modeled using molecular docking and provides an understanding of the compound mode of action. The results point to gossypol (S2303) as a promising antimicrobial compound that inhibits cell division by affecting FtsZ polymerization and has potential to be developed into an effective antimicrobial drug by chemical modification to minimize its cytotoxic effects in eukaryotic cells that were identified in this work.

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Natural Polyphenol-Containing Gels against HSV-1 Infection: A Comparative Study.

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