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IntroductionFunctional cure has been proposed as an alternative to lifelong antiretroviral therapy and therapeutic vaccines represent one of the most promising approaches.Materials and MethodsWe conducted a double-blind randomized placebo-controlled clinical trial to evaluate the safety, immunogenicity, and effect on viral dynamics of a therapeutic vaccine produced with monocyte-derived dendritic cells (MD-DC) loaded with a high dose of heat-inactivated autologous (HIA) HIV-1 in combination with pegylated interferon alpha 2a (IFNα-2a) in people with chronic HIV-1.ResultsTwenty-nine male individuals on successful ART and with CD4+ ≥450 cells/mm3 were randomized 1:1:1:1 to receive three ultrasound-guided inguinal intranodal immunizations, one every 2 weeks: (1) vaccine ~107 MD-DC pulsed with HIA-HIV-1 (1010 HIV RNA copies) (n = 8); (2) vaccine plus three doses of 180 mcg IFNα-2a at weeks 4–6 (n = 6); (3) placebo = saline (n = 7); and (4) placebo plus three doses of 180 mcg IFNα-2a (n = 8). Thereafter, treatment was interrupted (ATI). Vaccines, IFNα-2a, and the administration procedures were safe and well tolerated. All patients’ viral load rebounded during the 12-week ATI period. According to groups, changes in viral set-point between pre-ART and during ATI were not significant. When comparing all groups, there was a tendency in changes in viral set-point between the vaccine group vs. vaccine + IFNα-2a group (>0.5log10p = 0.05). HIV-1-specific T-cell responses (IFN-ƴ Elispot) were higher at baseline in placebo than in the vaccine group (2,259 ± 535 vs. 900 ± 200 SFC/106 PBMC, p = 0.028). A significant difference in the change of specific T-cell responses was only observed at week 4 between vaccine and placebo groups (694 ± 327 vs. 1,718 ± 282 SFC/106 PBMC, p = 0.04). No effect on T-cell responses or changes in viral reservoir were observed after INFα-2a administration.DiscussionResults from this study show that intranodally administered DC therapeutic vaccine in combination with IFNα-2a was safe and well-tolerated but had a minimal impact on viral dynamics in HIV-1 chronic infected participants.Clinical Trial Registration(www.ClinicalTrials.gov), identifier NCT02767193

Abatia americana is a Brazilian species that has yet to be the subject of scientific investigation. However, it represents a potential source of new antibacterial and anticancer drugs, given it belongs to the Salicaceae family. The objective of this study was to investigate the potential biological activities and chemical composition of this species. The chemical characterisation was conducted using UPLC-QTOF-MS/MS. The cytotoxicity was evaluated using the sulforhodamine B method and the antibacterial activity was determined through a microdilution assay. Within the fractions obtained, namely hexane (HF), ethyl acetate (EF), butyl alcohol (BF), and hydromethanolic (HMF), 37 compounds were identified. The fractions showed better antibacterial activity against Staphylococcus aureus and Listeria monocytogenes . Those with greater polarity (HMF; BF) showed better results, with lower minimum bactericidal concentration (MBC) and higher selectivity index. They also demonstrated cytotoxic and antiproliferative action for T24 tumour lineage. Among the fractions, the most promising is the HMF fraction, which showed satisfactory selectivity and did not inhibit normal cell proliferation. This is also the first time that biological effects have been reported for this species.

Melanoma, primarily caused by solar ultraviolet (UV) radiation, can be prevented by the use of sunscreens. However, the use of synthetic sunscreens raises environmental concerns. Natural compounds with antioxidant photoprotective properties and cytotoxic effects against cancer cells can be promising for the prevention and treatment of melanoma with less environmental effect. This study focuses on Melaleuca leucadendron essential oil (EO) for photoprotection and antitumor applications. EO was hydrodistilled from M. leucadendron leaves with a 0.59% yield. Gas chromatography-mass spectrometry detected monoterpenes and sesquiterpenes. Nanoemulsions were prepared with (NE-EO) and without EO (NE-B) using the phase inversion method, showing good stability, spherical or oval morphology, and a pseudoplastic profile. Photoprotective activity assessed spectrophotometrically showed that the NE-EO was more effective than NE-B and free EO. Antioxidant activity evaluated by DPPH and ABTS methods indicated that pure and nanoemulsified EO mainly inhibited the ABTS radical, showing IC 50 40.72 and 5.30 µg/mL, respectively. Cytotoxicity tests on L-929 mouse fibroblasts, NGM human melanocyte, B16-F10 melanoma, and MeWo human melanoma revealed that EO and NE-EO were more cytotoxic to melanoma cells than to non-tumor cells. The stable NE-EO demonstrates potential for melanoma prevention and treatment. Further research is required to gain a better understanding of these activities.

The treatment of skin and soft tissue infections (SSTIs) can be challenging due to bacterial resistance, particularly from strains like MRSA and biofilm formation. However, combining conventional antibiotics with natural products shows promise in treating SSTIs. The objective of this study is to develop a nanoemulsion-based hydrogel containing Protium spruceanum extract and mupirocin and evaluate its potential for the treatment of SSTIs. The nanoemulsion was obtained by phase inversion and subsequently characterized. The antibacterial activity was evaluated in vitro against S. aureus MRSA, including the synergism of the combination, changes in membrane permeability using flow cytometry, and the anti-biofilm effect. In addition, the irritative potential was evaluated by the HET-CAM assay. The combination exhibited synergistic antibacterial activity against S. aureus and MRSA due to the extract enhancing membrane permeability. The hydrogel demonstrated suitable physicochemical properties, inhibited biofilm formation, and exhibited low irritation. The formulation was nanometric (176.0 ± 1.656 nm) and monodisperse (polydispersity index 0.286 ± 0.011). It exhibited a controlled release profile at 48 h and high encapsulation efficacy (94.29 ± 4.54% for quercitrin and 94.20 ± 5.44% for mupirocin). Therefore, these findings suggest that the hydrogel developed could be a safe and effective option for treating SSTIs., Competing Interests: The authors declare no conflicts of interest.

Fridericia formosa (Bureau) L.G. Lohmann (Bignonaceae) is a neotropical liana species found in the Cerrado biome in Brazil. It has been of great interest to the scientific community due to its potential as a source of new antivirals, including xanthones derived from mangiferin. In this context, the present study aimed to characterize and quantify the xanthones present in the ethanol extract of this species using high performance liquid chromatography. Additionally, the antiviral activity against Chikungunya, Zika, and Mayaro viruses was evaluated. The chromatographic analyses partially identified twenty-six xanthones, among which only fourteen had already been described in the literature. The xanthones mangiferin, 2'-O-trans-caffeoylmangiferin, and 2'-O-trans-coumaroylmangiferin, are present in higher quantities in the extract, at concentrations of 9.65%, 10.68%, and 3.41% w/w, respectively. In antiviral assays, the extract inhibited the multiplication cycle only for the Mayaro virus with a CE 50 of 36.1 μg/mL. Among the isolated xanthones, 2'-O-trans-coumaroylmangiferin and 2'-O-trans-cinnamoylmangiferin inhibited the viral cytopathic effect with CE 50 values of 180.6 and 149.4 μg/mL, respectively. Therefore, the extract from F. formosa leaves, which has a high content of xanthones, has antiviral potential and can be a source of new mangiferin derivatives., (© 2024. The Author(s).)

Chagas disease (CD) is a worldwide public health problem, and the drugs available for its treatment have severe limitations. Red propolis is a natural extract known for its high content of phenolic compounds and for having activity against T. cruzi . The aim of this study was to investigate the trypanocidal potential of red propolis to isolate, identify, and indicate the mode of action of the bioactive compounds. The results revealed that the total phenolic content was 15.4 mg GAE/g, and flavonoids were 7.2 mg QE/g. The extract was fractionated through liquid-liquid partitioning, and the trypanocidal potential of the samples was evaluated using the epimastigote forms of the Y strain of T. cruzi . In this process, one compound was characterized by MS, 1 H, and 13 C NMR and identified as vestitol. Cytotoxicity was evaluated employing MRC-5 fibroblasts and H9C2 cardiomyocytes, showing cytotoxic concentrations above 15.62 μg/mL and 31.25 μg/mL, respectively. In silico analyses were applied, and the data suggested that the substance had a membrane-permeation-enhancing effect, which was confirmed through an in vitro assay. Finally, a molecular docking analysis revealed a higher affinity of vestitol with farnesyl diphosphate synthase (FPPS). The identified isoflavan appears to be a promising lead compound for further development to treat Chagas disease.

Modified release systems depend on the selection of an appropriate agent capable of controlling the release of the drug, sustaining the therapeutic action over time, and/or releasing the drug at the level of a particular tissue or target organ. Polyethylene glycol 4000 (PEG 4000) is commonly employed in drug release formulations while polymethyl methacrylate (PMMA) is non-toxic and has a good solubility in organic solvents. This study aimed at the incorporation of ketoconazole in PMMA-g-PEG 4000 and its derivatives, thus evaluating its release profile and anti- Candida albicans and cytotoxic activities. Ketoconazole was characterized and incorporated into the copolymers. The ketoconazole incorporated in the copolymer and its derivatives showed an immediate release profile. All copolymers with ketoconazole showed activity against Candida albicans and were non-toxic to human cells in the entire concentration tested.

Bladder cancer has a high incidence and recurrence rate among patients worldwide. This study aimed to evaluate the cytotoxic activity of fractions of Sambucus nigra L. flower extracts on bladder carcinoma cells (T24 cells) and human fibroblast cells (MRC-5). The butanolic fraction (F-BuOH) was characterized by UPLC-DAD-MS/MS and nine flavonoids were identified. Rutin was the major compound. The cytotoxic activity of this fraction was observed in the T24 cells but not in MRC-5 cells, indicating selectivity. F-BuOH was incorporated in micellar solutions of Pluronic® F127 and cytotoxic effect for T24 cells was observed again. In vitro assay demonstrated a controlled release of the fraction from the micelles. The results obtained showed that flavonoids are the possible responsible for cytotoxic activity in bladder carcinoma cells. In addition, micellar solutions act together to increase the action of the butanolic fraction.

The broad pharmacological spectrum of plants is related to their secondary metabolism, which is responsible for the synthesis of different compounds that have multiple effects on cellular physiology. Among the biological effects presented by phytochemicals, their use for the prevention and treatment of cancer can be highlighted. This occurs due to several mechanisms of antitumor action demonstrated by these compounds, including regulation of the cell signaling pathways and inhibition of tumor growth. In this way, long non-coding RNAs (lncRNAs) appear to be promising targets for the treatment of cancer. Their deregulation has already been related to a variety of clinicalpathological parameters. However, the effects of secondary metabolites on lncRNAs are still restricted. For this reason, the present review aimed to gather data on phytochemicals with action on lncRNAs in order to confirm their possible antitumor potential. According to the literature, terpenoid and flavonoid are the main examples of secondary metabolites involved with lncRNAs activity. In addition, the lncRNAs H19, CASC2, HOTAIR, NKILA, CCAT1, MALAT1, AFAP1-AS1, MEG3, and CDKN2B-AS1 can be highlighted as important targets in the search for new anti-tumor agents since they act as modulating pathways related to cell proliferation, cell cycle, apoptosis, cell migration and invasion. Finally, challenges for the use of natural products as a commercial drug were also discussed. The low yield, selectivity index and undesirable pharmacokinetic parameters were emphasized as a difficulty for obtaining these compounds on a large scale and for improving the potency of its biological effect. However, the synthesis and/or development of formulations were suggested as a possible approach to solve these problems. All of these data together confirm the potential of secondary metabolites as a source of new anti-tumor agents acting on lncRNAs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim of this study was to analyse the antitumor effect of the Cymbopogon densiflorus essential oil in silico and in vitro on bladder cancer cells RT4 and T24, with different TP53 status. The oil was extracted by hydrodistillation and the gas chromatography coupled to the mass spectrometry was used for characterisation. In silico analysis was carried out by Pass online software. Cytotoxicity, cell proliferation, cell cycle progression, apoptosis and wound healing assays were performed. Five major compounds were identified. In silico analysis showed that major compounds present high potential for antitumor activities. The treatment with C. densiflorus essential oil reduced cell viability of bladder cancer cells. Only in wild-type cells, the increase of apoptosis rates and the decrease of cell migration were observed. In conclusion, the C. densiflorus essential oil presents antitumor effects on TP53 wild-type and mutated bladder cancer cells, however, the mechanism of action is TP53 status-dependent.[Figure: see text].

The new severe acute respiratory syndrome coronavirus (SARS-CoV-2) recently emerged as a worrying pandemic, with many confirmed cases and deaths globally. Therefore, there is a clear need for identifying effective therapeutic options and a review of secondary metabolites related to Brazilian herbal medicines was performed as a strategy for the discovery of new antiviral agents. To confirm this potential, an in silico screening of the identified compounds identified was also evaluated. The review was performed by the PubMed database and the selected natural compounds were subjected to in silico analysis such as QSAR, molecular docking and ADMET. 497 secondary metabolites were identified from 23 species. The in silico assays indicated 19 potential anti-SARS-CoV-2 compounds, being triterpenes and phenolic compounds. The indicated compounds showed a high affinity with proteins considered as the main molecular targets against SARS-CoV-2 and parameters indicated low toxicity. In addition to Brazilian medicinal plants, these compounds can be found in other species and they can be a base for the synthesis of other anti-COVID-19 drugs. Therefore, this review is important to conduct researches that address the emerging need for drugs in COVID-19 treatment., (© 2021 John Wiley & Sons Ltd.)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China and its spread worldwide has become one of the biggest health problem due to the lack of knowledge about an effective chemotherapy. Based on the current reality of the SARS-CoV-2 pandemic, this study aimed to make a review literature about potential anti-coronavirus natural compounds guided by an in silico study. In the first step, essential oils from native species found in the Brazilian herbal medicine market and Brazilian species that have already shown antiviral potential were used as source for the literature search and compounds selection. Among these compounds, 184 showed high antiviral potential against rhinovirus or picornavirus by quantitative structure-activity relationship analysis. ( E )-α-atlantone; 14-hydroxy-α-muurolene; allo-aromadendrene epoxide; amorpha-4,9-dien-2-ol; aristochene; azulenol; germacrene A; guaia-6,9-diene; hedycaryol; humulene epoxide II; α-amorphene; α-cadinene; α-calacorene and α-muurolene showed by a molecular docking study the best result for four target proteins that are essential for SARS-CoV-2 lifecycle. In addition, other parameters obtained for the selected compounds indicated low toxicity and showed good probability to achieve cell permeability and be used as a drug. These results guided the second literature search which included other species in addition to native Brazilian plants. The majority presence of any of these compounds was reported for essential oils from 45 species. In view of the few studies relating essential oils and antiviral activity, this review is important for future assays against the new coronavirus., Supplementary Information: The online version contains supplementary material available at 10.1007/s11101-021-09754-4., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2021.)

Plants may contain beneficial or potentially dangerous substances to humans. This study aimed to prepare and evaluate a new drug delivery system based on a glass-ionomer-Brazilian pepper extract composite, to check for its activity against pathogenic microorganisms of the oral cavity, along with its in vitro biocompatibility. The ethanolic Brazilian pepper extract (BPE), the glass-ionomer cement (GIC) and the composite GIC-BPE were characterized by scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and thermal analysis. The BPE compounds were identified by UPLC-QTOF-MS/MS. The release profile of flavonoids and the mechanical properties of the GIC-BPE composite were assessed. The flavonoids were released through a linear mechanism governing the diffusion for the first 48 h, as evidenced by the M t /M ∞ relatively to [Formula: see text], at a diffusion coefficient of 1.406 × 10 -6  cm 2  s -1 . The ATR-FTIR analysis indicated that a chemical bond between the GIC and BPE components may have occurred, but the compressive strength of GIC-BPE does not differ significantly from that of this glass-ionomer. The GIC-BPE sample revealed an ample bacterial activity at non-cytotoxic concentrations for the human fibroblast MRC-5 cells. These results suggest that the prepared composite may represent an alternative agent for endodontic treatment.

Essential oils are potential antimicrobial agents and can be used as active ingredients in the pharmaceutical, food and cosmetics industries. This work intends to evaluate the antibacterial activity and design a strategy for the proposition of the mechanism of action of Melaleuca leucadendra essential oil. Optimum concentration of the bacteria and the phase where they had the highest pathogenic activity were determined. Results show that for each microorganism it is necessary to use a different concentration at the time of adjusting the initial inoculum, and that the time to achieve exponential growth phase varies from one to the other. M. leucadendra essential oil demonstrated in vitro antimicrobial properties. This oil was chemically characterized and the main compounds were evaluated by their mechanism of antibacterial action based on structure-activity analysis. The mechanism is related to the increase of bacteria cell membrane permeability. This indication was confirmed by flow cytometry and transmission electronic microscopy. Thus, in silico analysis is an important tool in the search for new antimicrobial agents and these results showed that M. leucadendra essential oil may be useful on the development of new chemotherapies or food preservation systems.

The research for new treatments of skin and soft tissue infections (SSTIs) is important due to their high prevalence and number of hospitalizations. The purpose of this review is to address the pathophysiology of SSTIs to highlight the advantages of herbal medicines to their treatment, showing examples of species and compounds with multi-targets action. SSTIs have a complex physiopathology involving the microorganism, as well as inflammation and difficult healing. Therefore, antimicrobial, anti-inflammatory, antioxidant and healing activities are an approach possible for their treatment. Herbal medicines have a wide diversity of biological compounds, mainly phenolic compounds that may act on different targets and also have synergism between them. Therefore, a single medicine may have the four key activities that allied allow eliminating the infection, control the inflammation process and accelerating the healing process, preventing complications with chronic infections., (© 2019 John Wiley & Sons, Ltd.)

The physicochemical characteristics of nanostructured suspensions are important prerequisites for the success of new drug development. This work aimed to develop nanometric systems containing Cymbopogon densiflorus leaf essential oil and to evaluate their antimicrobial activity. The essential oil was isolated by hydrodistillation from leaves and analyzed by GC-MS. The main constituents were found to be trans - p -mentha-2,8-dien-1-ol, cis - p -mentha-2,8-dien-1-ol, trans - p -mentha-1(7),8-dien-2-ol, cis -piperitol, and cis - p -mentha-1(7),8-dien-2-ol. In silico prediction analysis suggested that this oil possesses antimicrobial potential and the main mechanism of action might be the peptidoglycan glycosyltransferase inhibition. Nanoemulsions were prepared by the phase inversion method, and liposomes were made by the film hydration method. Qualitative evaluation of the antimicrobial activity was performed by the diffusion disk assay with 24 microorganisms; all of them were found to be sensitive to the essential oil. Subsequently, this property was quantified by the serial microdilution technique, where the nanoformulations demonstrated improved activity in comparison with the free oil. Bactericidal action was tested by the propidium iodide method, which revealed that free essential oil and nanoemulsion increased cytoplasmic membrane permeability, while no difference was observed between negative control and liposome. These results were confirmed by images obtained using transmission electron microscopy. This study has shown an optimization in the antimicrobial activity of C. densiflorus essential oil by a nanoemulsion and a liposomal formulation of the active substances.

Ethnopharmacological Relevance: Protium spruceanum (Burseraceae) is used in Brazilian traditional medicine as anti-inflammatory, but the factors involved in this activity were not yet characterized., Aims of the Study: analyze the aspects involved in the anti-inflammatory activity of polar fractions obtained from extracts of leaves and branches., Materials and Methods: Hydromethanolic fraction was obtained by liquid-liquid partition from crude ethanolic extract and its compounds were identified by LC-DAD-MS. Activity tests were performed using LPS + IFN-γ stimulated J774A.1 macrophages. Cytokines were evaluated by CBA kit, NO by Griess method, ROS by DCFH-DA, N-acetylglucosaminidase (NAG) activity by spectrophotometric method, matrix-metalloproteinase (MMP-9) activity by zymography, inducible nitric oxide synthase (iNOS) expression by immunofluorescence and cyclooxygenase (COX-2) expression by Western blot., Results: Fractions induced an increase of IL-6 and IL-10 which leads to the control of pro-inflammatory cytokines levels. The treatment with the fractions also reduced NO production at all concentrations tested in all evaluated periods. ROS production by the macrophages was inhibited by the treatment and the leaves fraction showed the best results with a lower concentration than that observed for the branches. The enzymes assays showed that leaves fraction inhibited NAG and MMP-9 activities, as well as, iNOS and COX-2 expression. These activities can be associated with the presence of procyanidin, catechin, rutin, quercitrin, isoquercitrin and kaempferol-3-O-rhamnoside, major compounds that were identified in the fraction., Conclusions: Anti-inflammatory activity of P. spruceanum is associated to an immunomodulatory effect that leads to inhibition of ROS, NO, NAG, MMP-9, COX-2 and iNOS., (Copyright © 2019. Published by Elsevier B.V.)

Propolis has demonstrated potential use as food preservative but it presents strong and unpleasant flavor that alters the sensory characteristics foods. A nanoemulsion was proposed to carry the Brazilian propolis extracts for use as natural food preservative. Antimicrobial and antioxidant activities and chemical constituents of the extracts were investigated. The latter were made by sequential extraction using different solvents (hexane, ethyl acetate and ethanol). Antimicrobial activity was evaluated by agar diffusion and microdilution methods and antioxidant activity by DPPH and ABTS assays. Extracts showed antibacterial and antioxidant activity, highlighting the ethanolic which contained artepillin-C, kaempferide, drupanin and p-coumaric acid as main compounds by LC-MS analysis. The nanoemulsion developed by phase inversion method was characterized and stable under thermal-stress and centrifugation conditions. Biological properties evaluated were effectively maintained by the formulation. It was concluded that the nanoemulsion can be used as a food preservative, preventing degradation and masking the propolis off-flavor., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The crude ethanol extract (CEE) and fractions from branches of Protium spruceanum were subjected to antibacterial and cytotoxicity assays. Compounds of the most active fraction were identified by GC-MS and LC-MS. CEE was active against 19 bacteria and the ethyl acetate fraction (EAF) showed the lowest minimum bactericidal concentration (MBC 0.3-80.0 mg/mL). Through time-kill assay was observed that EAF induced rapid bactericidal effect against Staphylococcus saprophyticus. The cytotoxicity tests against L929 fibroblasts showed great potential of EAF on the treatment of infections caused by five bacteria (MBC < IC 50 ). The results provide in vitro scientific support to the possible application of branches of P. spruceanum as antimicrobial agent that may contribute for treatment of infections.