Background and aim: Metabolic disturbances are known for their increasing epidemiological importance. Ilex paraguariensis presents a potential option for mitigating lipid metabolism imbalance. ...However, most of the literature to date has not considered sex bias. This study aimed to evaluate the effect of Ilex paraguariensis on the metabolism of different adipose tissue depots in males and females. Experimental procedure: After ovariectomy, female Wistar rats received daily treatment with the extract (1 g/kg) for forty-five days. Biochemical serum parameters and tissue metabolism were evaluated. Oxidation, lipogenesis and lipolysis were evaluated in brown, white visceral, retroperitoneal and gonadal adipose tissues. Results and conclusion: The results showed that treatment with the extract led to a reduced weight gain in ovariectomised females in comparison to control. The triglyceride concentration was decreased in males. Glucose oxidation and lipid synthesis in visceral and retroperitoneal adipose tissues were restored in ovariectomised females after treatment. The response to epinephrine decreased in visceral adipose tissue of control males; however, lipolysis in females did not respond to ovariectomy or treatment. These findings highlight the enormous potential effects of I. paraguariensis on lipid metabolism, modulating lipogenic pathways in females and lipolytic pathways in males. Furthermore, the sex approach applied in this study contributes to more effective screening of the effects of I. paraguariensis bioactive substances.
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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.
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.
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
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.
Rosmarinic acid (RA) is a phenolic compound that presents well-documented anti-inflammatory, antioxidant and antitumor activities, and based on its pharmacological potential and poor bioavailability, ...several solid dosage forms have been developed to RA delivery. Therefore, in literature, there are no reports about RA compatibility with excipients. In this regard, the aim of the present study was to evaluate, for the first time, the compatibility of RA with excipients commonly used in solid dosage forms at a 1:1 (RA:excipient) ratio using differential scanning calorimetry (DSC), thermogravimetry (TG), Fourier-transform infrared (FTIR), solid-state nuclear magnetic resonance (ssNMR), and isothermal stress testing (IST) coupled with liquid chromatography (LC). The excipients selected were hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), lactose monohydrate (LAC), polyvinylpyrrolidone (PVP), talc (TALC), croscarmellose sodium (CCS), and magnesium stearate (MgSTE). According to DSC results, physical interactions were found between RA and HPMC, LAC, CCS, and MgSTE. The TG analyses confirmed the physical interactions and suggested chemical incompatibility. FTIR revealed physical interaction of RA with TALC and MgSTE and the ssNMR confirmed the physical interaction showed by FTIR and excluded the presence of chemical incompatibility. By IST, the greatest loss of RA content was found to CCS and MgSTE (>15%), demonstrating chemical incompatibilities with RA. High temperatures used in DSC and TG analyses could be responsible for incompatibilities in binary mixtures (BMs) with HPMC and LAC, while temperature above 25 °C and presence of water were factors that promote incompatibilities in BMs with CCS and MgSTE. Overall results demonstrate that RA was compatible with MCC and PVP.
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.
Achyrocline satureioides, popularly known as “marcela”, is a medicinal plant found in South America. This plant is rich in flavonoids, which have been reported to exert numerous biological ...activities. The aim of this study was to purify, identify and evaluate the mechanisms underlining anticancer activity of A. satureioides flavonoids in glioma cell lines (U87, U251 and C6) as well as their comparative toxicity in normal brain cells (primary astrocytes, neurons and organotypic hippocampal cultures). The main flavonoids present in A. satureioides are luteolin, quercetin, 3-O-methyl-quercetin and achyrobichalcone, the later a very unique metabolite present in this plant. Isolated flavonoids as well as A. satureioides extracts reduced proliferation and clonogenic survival, and induced apoptosis of glioma cell lines. In addition, A. satureioides flavonoids potentiated the cytotoxic effect and apoptosis induction by the glioma chemotherapeutic temozolomide (TMZ). Importantly, A. satureioides flavonoids were less cytotoxic to astrocytes, neuron:astrocytes co-cultures and hippocampal cultures if compared to gliomas. Investigation of 10 cancer-related pathways showed a reduced activation of MYC and the Map kinases ERK and JNK by A. satureioides flavonoid-enriched extract, an effect not observed when individual flavonoids were evaluated. Altogether, the herein presented results show that A. satureioides extract possesses a combination of flavonoids, some unique for this plant, which have synergistic anticancer activity and potential for further studies in vivo.
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•Isolated flavonoids from marcela reduced proliferation and clonogenic survival, and induced apoptosis of glioma cell lines;•Marcela flavonoids potentiated the cytotoxic effect and apoptosis induction by the glioma chemotherapeutic temozolomide;•Flavonoid combinations increased the antiproliferative activities.
Rosmarinic acid (RA) lipid-nanotechnology-based delivery systems associate with mucoadhesive biopolymers for nasal administration has arisen as a new promising neuroprotective therapy for ...neurodegenerative disorders (ND). We have previously demonstrated the glioprotective effect of chitosan-coated RA nanoemulsions (RA CNE) against lipopolysaccharide (LPS)-induced damage in rat astrocyte primary culture. Here, we further investigate the protective effect of RA CNE nasal administration on LPS-induced memory deficit, neuroinflammation, and oxidative stress in Wistar rats, since these in vivo studies were crucial to understand the impact of developed delivery systems in the RA neuroprotective effects. The animals were treated through nasal route with RA CNE (2 mg·mL−1), free RA (2 mg·mL−1), blank CNE, and saline (control and LPS groups) administrations (n.a., 100 μL per nostril) twice a day (7 a.m./7 p.m.) for six days. On the sixth day, the animals received the last treatments and LPS was intraperitoneally (i.p.) administrated (250 μg·kg−1). Overall results, proved for the first time that the RA CNE nasal administration elicits a neuroprotective effect against LPS-induced damage, which was associated with increased 1.6 times recognition index, decreased 5.0 and 1.9 times in GFAP+ cell count and CD11b expression, respectively, as well as increased 1.7 times SH in cerebellum and decreased 3.9 times TBARS levels in cerebral cortex in comparison with LPS group. RA CNE treatment also facilitates RA bioavailability in the brain, confirmed by RA quantification. Free RA also demonstrates a protective effect in some studied parameters, although no RA was quantified in the brain.
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•LPS induced memory deficit, neuroinflammation and oxidative stress in Wistar rats.•RA CNE nasal administration exerts a neuroprotective potential.•RA CNE nasal administration increased recognition index and SH levels.•RA CNE nasal administration decreased TBARS levels, GFAP+ and CD11b expression.•RA CNE nasal administration also facilitates the CNS reach of RA.
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