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.

Brazilian essential oils as source for the discovery of new anti-COVID-19 drug: a review guided by in silico study.

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.

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].

Salt-dependent hypertension and inflammation: targeting the gut-brain axis and the immune system with Brazilian green propolis.

Systemic arterial hypertension (SAH) is a major health problem around the world and its development has been associated with exceeding salt consumption by the modern society. The mechanisms by which salt consumption increase blood pressure (BP) involve several homeostatic systems but many details have not yet been fully elucidated. Evidences accumulated over the last 60 decades raised the involvement of the immune system in the hypertension development and opened a range of possibilities for new therapeutic targets. Green propolis is a promising natural product with potent anti-inflammatory properties acting on specific targets, most of them participating in the gut-brain axis of the sodium-dependent hypertension. New anti-hypertensive products reinforce the therapeutic arsenal improving the corollary of choices, especially in those cases where patients are resistant or refractory to conventional therapy. This review sought to bring the newest advances in the field articulating evidences that show a cross-talking between inflammation and the central mechanisms involved with the sodium-dependent hypertension as well as the stablished actions of green propolis and some of its biologically active compounds on the immune cells and cytokines that would be involved with its anti-hypertensive properties.

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.

Functionalized rifampicin-loaded nanostructured lipid carriers enhance macrophages uptake and antimycobacterial activity.

Tuberculosis is an infectious bacterial disease that causes millions of deaths worldwide. Current treatment recommended by WHO is effective, however it is an extensive and arduous process associated to severe adverse effects, which induces a low patient compliance and the emerging of multidrug resistant tuberculosis. Thus, as a main goal of this study, rifampicin nanoparticles were surface functionalized with a tuftsin-modifed peptide to selectively recognize receptors located on infected alveolar macrophages, enhancing nanoparticles uptake by these cells and improving antimycobacterial activity. A tuftsin-based modified peptide was synthesized and successfully attached to nanoparticles interface (NP-pRIF). In parallel, nanoparticles without peptide were also developed for comparison (NP-RIF). Physicochemical characterization demonstrated that stable and monodisperse nanodelivery systems were obtained, with a controlled drug release profile and non-cytotoxic potential. Moreover, nanoparticles containing peptide were significantly more internalized by macrophages than nanoparticles without peptide over a wide range of time. Both nanoparticles were 2-fold more effective against M. tuberculosis than free rifampicin, suggesting NP-pRIF as a promising strategy for the management of tuberculosis treatment.

Effect of constituents from samaras of Austroplenckia populnea (Celastraceae) on human cancer cells.

BACKGROUND: Aiming the continuity of the studies of Austroplenckia populnea, Brazilian species of the Celastraceae family, in the present study, it was investigated the effect of crude extracts obtained with ethanol, ethyl acetate and chloroform and two purified constituents, proanthocyanidin A and 4'-O-methylepigallocatechin, both isolated from its samaras, on cancer cell proliferation assays. MATERIALS AND METHODS: The human cancer cells lines MCF-7 (ductal breast carcinoma), A549 (lung cancer), HS578T (ductal breast carcinoma) and non-cancer HEK293 (embryonic kidney cells) were treated with different concentrations of extracts and constituents and the effect was observed through the acid phosphatase method. The chemical structures of the purified compounds were identified by the respective IR and (1)H and (13)C nuclear magnetic resonance spectral data. RESULTS: While crude extracts from samaras of the folk medicine A. populnea can trigger cell proliferative effects in human cell lines, the purified compounds (proanthocyanidin A and 4'-O-methyl-epigallocatechin) isolated from the same extracts can have an opposite (anti-proliferative) effect. CONCLUSION: Based on the results, it was possible to suggest that extracts from samaras of A. populnea should be further investigated for possible cancer-promoting activities; and the active extracts can also represent a source of compounds that have anti-cancer properties.

Evaluation of short cycles of ultrasound application in nanoemulsions to obtain nanocapsules.

Ultrasound is widely used in several chemical reactions and other process, including production of nanocapsules by in situ polymerization. In this work, the main objective was to evaluate the impacts and viability of successive ultrasound application in nanoemulsions to obtain nanocapsules. Initiator potassium persulfate (KPS) concentration, number of ultrasound cycles and reaction time influences on polymerization efficiency and droplet size were evaluated. This work revealed the successful in situ production of nanocapsules using successive shorts cycles of ultrasound. Number of cycles was the only parameter that not exerted significant influence in polymerization yield. Particle size decay was observed in all nanoemulsions after the first ultrasound application, the same was not observed in further cycles. Gravimetric assessment showed remarkable increase of monomer conversion, indicating that once started polymerization continued at least until 28 days after ultrasound application. Concluding, ultrasound short cycles can be used with no harm to formulation, if carefully performed and, furthermore is a potential cost-effective route for polymerization reactions.

Influence of surfactant on the thermal behavior of marigold oil emulsions with liquid crystal phases.

Vegetable oils have been largely consumed owing to the interest of pharmaceutical and cosmetic industries in using natural raw materials. The production of stable emulsions with vegetable oils challenges formulators due to its variability in composition and fatty acids constitution within batches produced. In the present work, it was studied that the influence of the size of carbon chain and the number of ethylene oxide moieties of the surfactant on the thermal behavior of eight emulsions prepared with marigold oil stabilized by liquid crystal phases. Differential scanning calorimetry (DSC) was used to determine the thermal behavior of the emulsions. The ratio of bound water was calculated, being between 29.0 and 42.0%, confirming the extension of the liquid-crystalline net in the external phase. Changing the lipophilic surfactant from Ceteth-2 to Steareth-2, there was an increase in the temperature of phase transition of the liquid crystal influencing the system stability. Calorimetric study is very useful in understanding the performance of liquid crystals with the increase of temperature and to estimate emulsions stability.