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•Chitosan-coated RA nanoemulsion was successfully optimized using Box-Behnken design.•Mucoadhesive potential from chitosan-coated RA nanoemulsion was demonstrated.•Adequate ...physicochemical characteristics and prolonged RA release was also observed.•Long-lasting permeation and higher RA retention in porcine nasal mucosa was achieved.•Safety profile from chitosan-coated RA nanoemulsion was investigated in fibroblasts.
Mucoadhesive chitosan-coated nanoemulsions for rosmarinic acid (RA) nasal delivery were optimized. The optimum ratio between the formulation components that led to minimum droplet size and PDI, and maximal ζ-potential and RA content was obtained using Box-Behnken design (BBD). Optimized conditions were 8.5% oil phase (w/v), 3:10 lecithin to oil phase ratio (w/w), and 0.1% chitosan final concentration (w/v). Physicochemical characterization, mucoadhesion measurement, in vitro release and permeation/retention were performed. Optimized chitosan-coated RA nanoemulsions presented adequate physicochemical characteristics, high mucoadhesive potential, prolonged drug release, and long-lasting permeation time with a higher RA penetration/retention through porcine nasal mucosa. Cell viability and death by necrosis in fibroblasts cells were also evaluated to investigate the formulations safety. Formulations did not induce cytotoxicity following 24 h (3.125–50 μM) or 48 h (3.125–25 μM) of treatments. Overall results demonstrated that optimized chitosan-coated nanoemulsion showed to be a suitable carrier for RA nasal delivery aiming neuroprotective therapies.
Neurodegenerative disorders (ND) are characterized by slow and progressive neuronal dysfunction induced by the degeneration of neuronal cells in the central nervous system (CNS). Recently, the ...neuroprotective effects of natural compounds with anti-inflammatory and antioxidant activities has been clearly demonstrated. This appears to be an attractive therapeutic approach for ND, particularly regarding the use of polyphenols. In this review, we present an overview of the neuroprotective potential of rosmarinic acid (RA) and discuss the use of nanotechnology as a novel approach to treating ND. RA presents a variety of biological important activities, i.e. the modulation of pro-inflammatory cytokine expression, prevention of neurodegeneration and damage reduction. However, its poor bioavailability represents a limitation in terms of pharmacodynamics. In this sense, nanotechnology-based carriers could allow for the administration of higher but still safe amounts of RA, aiming for CNS delivery. Nasal administration could be a pleasant route for delivery to the CNS, as this represents a direct route to the CNS. With these advantages, RA-loaded nanotechnology-based therapy through the nasal route could be promising approach for the treatment of ND.
•RA exhibits anti-inflammatory and antioxidant activities.•RA exhibits neuroprotective potential for treating ND.•RA present poor oral bioavailability and permeability in CNS.•Nanotechnology-based therapy emerges as a promising strategy for RA.•RA nasal delivery could also be a pleasant route for CNS delivery.
Monteverdia ilicifolia
(Mart. ex Reissek) Biral, Celastraceae (Syn.
Maytenus ilicifolia
Mart. ex Reissek), is used in Brazil as a folk medicine to treat gastrointestinal disorders. The health ...benefits derived from consuming
M. ilicifolia
have been attributed to its high content of phenolic compounds, such as flavonoids, and the corresponding condensed tannins. The presence of other classes of active molecules including terpenes and polysaccharides has also been described in the literature. It is important to mention that this species is presented in the National List of Essential Medicines published by the Brazilian Health Ministry, including some pharmaceutical forms which needs to be analyzed carefully. Thus, the aim of this study was to identify and analyze scientific publications on
M. ilicifolia
highlighting botanical aspects, traditional uses, chemical composition, and technological approaches as a source of systematic and critical information about the plant and its derived products. PubMed and Clarivate Analytics Web of Science databases were used. A total of 224 articles were included in the study. A trend toward an increasing number of publications on
M. ilicifolia
between 2006 and 2012 was evident, and its medicinal applications and biological activity against gastric ulcers. Catechin and epicatechin flavonoids were the major phytoconstituents of this species, characterized as monomers or polymers forming condensed tannins. The triterpenoid friedelin is currently the subject of many studies due to its pharmacological potential; however, it is unlikely that this compound could be responsible for the activities attributed to the traditional use of
M. ilicifolia
because of its high lipophilicity. This review provides the first detailed overview of the taxonomy of
M. ilicifolia
, and its ethnobotanical, phytochemical, and technological aspects and pharmaceutical formulation for the treatment of gastric ulcers.
Graphical abstract
Rosmarinic acid (RA) is a natural polyphenolic compound with a well-documented neuroprotective effect mainly associated with its anti-inflammatory and antioxidant activities. Recently, our research ...group developed and optimized chitosan-coated RA nanoemulsions (RA CNE) intended to be used for nasal delivery as a new potential neuroprotective therapy. In this sense, the present study aimed to evaluate the protective and/or therapeutic potential of RA CNE in inflammation/oxidative stress induced by LPS (1 μg mL
−1
) in rat astrocyte primary cultures. In summary, pre-treatment with RA CNE before exposure to LPS (protective protocol) reduced significantly the LPS-induced alterations in astrocyte cell viability, proliferation, and cell death by necrosis, which was not observed in therapeutic protocol. RA CNE protective protocol also enhanced anti-oxidative status by ~ 50% by decreasing oxygen reactive species production and nitric oxide levels and preventing total thiol content decrease. Finally, our results demonstrate the protective effect of RA CNE in migratory activation and GFAP expression of reactive astrocytes. Overall, our findings indicate for the first time the RA CNE glioprotective potential, associated with an increase in cell viability and proliferation, a preventive effect on cellular death by necrosis, migratory ability and hypertrophic reactive astrocytes, and the reparation of astrocyte redox state.
Graphical Abstract
Objectives
Natural sources with antioxidant activity, such as rosmarinic acid (RA), have been considered as an interesting approach for the development of new anti‐ageing skin products. In this ...context, this study aimed to develop hydrogels containing RA‐loaded nanoemulsions and evaluate the effect of the addition of Tween® 80 (a nonionic cosurfactant) in formulations intended to be used for topical application.
Methods
Physico‐chemical characterization, in‐vitro release and skin retention/permeation from hydrogels of RA‐loaded nanoemulsions (containing or not Tween® 80) were evaluated. The RA‐loaded nanoemulsion safety profiles were also investigated in keratinocytes (HaCaT cells).
Key findings
It was observed that all formulations presented adequate physico‐chemical characterization for topical application. Furthermore, the results also demonstrated that the presence of Tween® 80 decreased the droplet size and polydispersity index of nanoemulsions and hydrogels. An extended RA release was noted for the hydrogels. However, when comparing the hydrogels, a positive effect of the presence of Tween® 80 on RA retention/permeation in total skin was seen. The RA‐loaded nanoemulsion safety profiles demonstrated a good tolerability (3.125–100 μm) in HaCaT cells.
Conclusions
The overall results demonstrated that the formulations developed in this study can be considered as a suitable carrier for RA in a topical application targeting new anti‐ageing skin care products.
Rosmarinic acid (RA) is a phenolic compound with remarkable antioxidant activity; however it presents low bioavailability. Cyclodextrin (CD) derivatives, such as hydroxypropyl-β-CD (HPβCD) and ...methyl-β-CD (MβCD), have been used to solve the low bioavailability of drugs, increasing their solubility or permeability. The aim of the present study was to investigate the complexation of RA with two derivative CDs, HPβCD and MβCD, and the resulting antioxidant activity. A phase-solubility study was performed to determine the stoichiometric ratio and apparent stability constant, and electrospray ionization coupled to mass spectroscopy (ESI–MS) was used to confirm the stoichiometric ratio. The freeze-dried (FD) complexes were characterized by liquid chromatography (LC), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and nuclear magnetic resonance (NMR). The antioxidant activity of RA and the FD complexes was evaluated by the DPPH method. A 2:1 (RA:CD) stoichiometric ratio and strong apparent constant stability were found for both complexes using a phase-solubility study, and ESI-MS spectra confirmed a signal corresponding to the 2:1 complex. The FD complexes showed high yield and RA content. The results of DSC, FTIR and SEM demonstrate changes in the physical-chemical characteristics of RA, suggesting its interaction with CDs. These interactions were confirmed by NMR, which revealed the formation of inclusion and non-inclusion complexes. The antioxidant activity of the RA:HPβCD and RA:MβCD FD complexes were higher than that of RA. The results suggest that FD complexes can be a technological approach to the development of formulations containing high content of RA with a view to increasing antioxidant potential.
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•RA forms complexes with HPβCD and MβCD at 2:1 (AR:CD) stoichiometric ratio.•The complexation was confirmed by ESI-MS, DSC, FTIR, SEM and NMR.•The complexes were characterized as inclusion and non-inclusion complex.•Antioxidant activity of RA was increased by complexation.
Hymenaea genus has been used in folk medicine in Brazil, but few studies investigated its toxicity profile. Thus, the aim of this study was to determine toxicological parameters of Hymenaea courbaril ...stem bark hydroalcoholic extract by utilizing three cell lines including murine macrophages (RAW 264.7), mouse fibroblast cells (L929) and human lung fibroblast (MRC-5), as well as Salmonella/microsome assay, and in vivo Caenorhabditis elegans model. The predominant detected phytoconstituents in the extract were coumarins, flavonoids, phenolics, tannins and saponins and by HPLC analysis, astilbin (AST) was found to be the main component. The DPPH assay demonstrated that H. courbaril hydroalcoholic extract exhibited potent antioxidant activity, with an IC
50
of 3.12 μg/ml. The extract at concentrations of 400 and 800 μg/ml decreased cell viability 48 hr after treatment in L929 and MRC-5 cell lines. In the Raw 264.7 strain, just the highest concentration (800 μg/ml) lowered cell viability within 48 hr following exposure. The concentration of 100 μg/ml did not markedly affect cell viability in the trypan blue assay. In the alkaline comet assay the extract was found to be non-genotoxic. In the Ames test, the extract exhibited low mutagenic potential without metabolic activation, since only the highest concentrations produced an effect. H. courbaril extract only affected the survival of C. elegans at concentrations of 800 and 1600 μl/ml. These findings demonstrate that H. courbaril extract appears to exert low toxicity as evidenced in vitro and mutagenicity assays; however, the biological relevance of the response of C. elegans survival to safety assessments needs further studies.
Pterostilbene is a natural constituent with numerous preventive and therapeutic properties used for treating a wide range of human diseases. It has been isolated from blueberries in high ...concentrations. A versatile specific-stability indicating liquid chromatography method for reliable quantitative determination of pterostilbene in blueberry extracts was developed. In the stability-indicating analysis, pterostilbene samples were exposed to stress conditions: temperature, UV light, and oxidative, acid and alkaline media. The robustness of the method was evaluated using a Box-Behnken experimental design. Pterostilbene was stable in acid and alkaline media, but unstable when exposed to oxidation, high temperature, and UV light. Using the proposed method, it was demonstrated that degradation products did not interfere in the analyte analysis. The method revealed to be simple, fast, selective, linear, precise and accurate for the quantitative analysis of pterostilbene in
Vaccinium myrtillus
extract. Besides being a specific-stability indicating method, it demonstrated to be applicable to quantify pterostilbene in pterostilbene:β-cyclodextrin complexes and pterostilbene:β-cyclodextrin:hydrophilic polymer ternary systems. These findings are relevant for the development of food, pharmaceutical or cosmetic products containing pterostilbene or blueberry extracts.
Pterostilbene is a natural constituent present in blueberries and other fruits, with several preventive and therapeutic properties for human health.
Isoflavones are a class of phytoestrogens that has been considered important raw material for healthcare products, mainly as dietary supplements for hormone replacement and active ingredients in skin ...care cosmetics. Because of this, many scientific reviews are found regarding the extraction, analysis methods and biological activities of these compounds. However, it is emphasized that, to date, no studies have been found concerning technological mapping of patents involving isoflavones.
The present study aimed to map patents covering the last 20 years of technology innovation comprising isoflavones. To that, a patent survey was conducted between the years of 1994–2014 in an international patent database (Espacenet) using the title's keywords: isoflavones, genistein, daidzein, glycitein, biochanin A and formononetin.
The resulting data allowed the identification of the major countries, universities and companies that invest in products containing these compounds. In addition, patents were separated into interest groups. The three clusters discussed in this study were: processes for obtaining enriched isoflavone fractions from different plant materials intended to healthcare products, such as dietary supplements; the use of isoflavones in cosmetic products; and the incorporation of isoflavones in micro and nanostructured systems to mask unpleasant tastes or overcome the low water solubility of bioactive forms. In conclusion, this study, along with other literature reviews, could assist in designing strategic research and worldwide development of new products containing isoflavones.
•A data survey of patents involving isoflavones was conducted.•The data were collected between the years of 1994–2014.•The patents were analyzed in accordance with three interesting clusters.•The main applicants of patents involving isoflavones were discussed.
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