Nanoemulsified Essential Oil of Melaleuca leucadendron Leaves for Topical Application: In Vitro Photoprotective, Antioxidant and Anti-Melanoma Activities.

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 IC50 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.

Anti-Inflammatory, Antimicrobial, Antioxidant and Photoprotective Investigation of Red Propolis Extract as Sunscreen Formulation in Polawax Cream.

Many activities have been described for propolis, including, antiviral, antibacterial, antifungal, anti-inflammatory, immunoregulatory, antioxidant and wound healing properties. Recently, propolis has been highlighted due to its potential application in the pharmaceutical and cosmetic industries, motivating a better understanding of its antioxidant and anti-inflammatory activities. Propolis and its main polyphenolic compounds presented high antioxidant activity, and effectiveness as broad spectrum UVB and UVA photoprotection sunscreens. Through a qualitative phytochemical screening, the ethanolic red propolis extracts (EEPV) (70% at room temperature and 70% at a hot temperature) presented a positive result for flavonoids and terpenoids. It presented an antioxidant activity for reducing 50% of DPPH of 17 and 12 µg/mL for extraction at room temperature and at a hot temperature, respectively. The UPLC-QTOF-MS/MS analysis allowed the annotation of 40 substances for EEPV-Heated and 42 substances for EEPV-Room Temperature. The IC50 results of the ABTS scavenging activity was 4.7 µg/mL for both extractions, at room temperature and at a hot temperature. Additionally, we also evaluated the cytotoxic profile of propolis extracts against macrophage (RAW 264.7 cells) and keratinocytes (HaCaT cells), which showed non-cytotoxic doses in cell viability assays even after a long period of exposure. In addition, propolis extracts showed antibacterial activity for Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), demonstrating potential biological activity for the creation of formulations aimed at disease control and prevention.

Modulation of Long Non-coding RNAs by Different Classes of Secondary Metabolites from Plants: A Mini-review on Antitumor Effects.

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.

Antitumor effect of Cymbopogon densiflorus (Linneu) essential oil in bladder cancer cells.

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].

Polymeric micelles containing resveratrol: development, characterization, cytotoxicity on tumor cells and antimicrobial activity

Antimicrobial and antitumor activities of resveratrol, a compound found mainly in grapes, have already been demonstrated. However, its low bioavailability is a limiting factor for therapeutic application. Polymeric micelles can be an approach to solve this problem since they can encapsulate hydrophobic substances. We developed and characterized micellar formulations containing resveratrol and evaluated their cytotoxic and antimicrobial effects. The formulations were prepared by the cold dispersion method with different concentrations of F127 (5 or 10% w/w) and resveratrol (500 or 5000 µM). The formulations were characterized according to size, polydispersity index, pH, encapsulation rate and in vitro release. Cytotoxic effect was evaluated on a bladder cancer cell line and antimicrobial effect was evaluated on E. coli, S. aureus and C. albicans. One of the formulations (10% w/w of F127 and 5000 µM of resveratrol) was a monodispersed solution with high encapsulation rate, thus it was chosen for the cytotoxicity and antimicrobial assays. MS- 10+RES-3 was able to preserve the antimicrobial and cytotoxic activity of resveratrol. This is the first study that evaluated antimicrobial potential and cytotoxicity of micelles containing resveratrol on bladder cancer cells and the results showed that micellar nanostructures could ensure the maintenance of the biological activity of resveratrol.

Antibacterial substances from leaves of Protium spruceanum (Burseraceae): in vitro and in silico evaluation

Due to the increase of bacterial resistance, the search for new antibiotics is necessary and the medicinal plants represent its most important source. The aim of this study was to evaluate the antibacterial property of extract and fractions from Protium spruceanum leaves, against pathogenic bacteria. By means of diffusion and microdilution assays, the crude extract was active against the nine bacteria tested being the hydromethanolic fraction the most active. During phytochemical procedures, procyanidin (1) and catechin (2) were identified as the main antibacterial constituents of this fraction. In silico results obtained using PASSonline tool indicated 1 and 2 as having good potential to interact with different targets of currently used antibiotics. These results no indicated potential to none DNA effect and indicated the cell wall as mainly target. Electrophoresis result supported that had no DNA damage. Cell wall damage was confirmed by propidium iodide test that showed increased membrane permeability and by cell surface deformations observed in scanning electronic microscopy. The in vitro assays together with the in silico prediction results establish the potential of P. spruceanum as source of antibacterial compounds that acts on important bacterial targets. These results contribute to the development of natural substances against pathogenic bacteria and to discovery of new antibiotics.

Development of propolis nanoemulsion with antioxidant and antimicrobial activity for use as a potential natural preservative.

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.