Schinopsis brasiliensis Engl. to combat the biofilm-dependents diseases in vitro

Dental caries and periodontal disease are the most prevalent of the biofilm-dependent diseases. With numerous side effects on the use of chlorhexidine, the search for new safe therapeutic alternatives for microorganisms involved with these diseases increases every day. This study aimed to evaluate the antimicrobial activity and cytotoxicity of extracts made from the bark of Schinopsis brasiliensis Engl. against five oral microorganisms and analyze their phytochemical and thermal degradation profile. The liquid-liquid partition was performed with hexane, chloroform and ethyl acetate. The identification and quantification of the chemical marker was done. Antimicrobial activity was evaluated based on the minimum inhibitory concentration. The cytotoxicity was analyzed based on the hemolysing potential of the samples. The thermal degradation profile was performed by two different methods. Gallic acid was identified as the main compound of the samples and showed the highest amount in the chloroform fraction. All samples were able to inhibit the growth of the microorganisms tested and showed no cytotoxicity. The ethanol extract absorbs less heat than the fractions. All samples exhibited exothermic peak consistent with degradation of gallic acid. Based on the results, the samples used are potential candidates for use in dental formulations for biofilm control

Anticancer and anti-inflammatory activities of a standardized dichloromethane extract from piper umbellatum l. leaves

Despite the advances in anticancer drug discovery field, the worldwide cancer incidence is remarkable, highlighting the need for new therapies focusing on both cancer cell and its microenvironment. The tumor microenvironment offers multiple targets for cancer therapy, including inflammation. Nowadays, almost 75% of the anticancer agents used in chemotherapy are derived from natural products, and plants are an important source of new promising therapies. Continuing our research on Piper umbellatum species, here we describe the anticancer (in vitro antiproliferative activity and in vivo Ehrlich solid tumor model) and anti-inflammatory (carrageenan-induced paw edema and peritonitis models) activities of a standardized dichloromethane extract (SDE) from P. umbellatum leaves, containing 23.9% of 4-nerolidylcatechol. SDE showed in vitro and in vivo antiproliferative activity, reducing Ehrlich solid tumor growth by 38.7 and 52.2% when doses of 200 and 400 mg/kg, respectively, were administered daily by oral route. Daily treatments did not produce signals of toxicity. SDE also reduced paw edema and leukocyte migration on carrageenan-induced inflammation models, suggesting that the anticancer activity of SDE from Piper umbellatum leaves could involve antiproliferative and anti-inflammatory effects. These findings highlight P. umbellatum as a source of compounds against cancer and inflammation2015CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES133897/2012-5sem informaçã

Chitosan-tripolyphosphate Nanoparticles As Arrabidaea Chica Standardized Extract Carrier: Synthesis, Characterization, Biocompatibility, And Antiulcerogenic Activity.

Natural products using plants have received considerable attention because of their potential to treat various diseases. Arrabidaea chica (Humb. & Bonpl.) B. Verlot is a native tropical American vine with healing properties employed in folk medicine for wound healing, inflammation, and gastrointestinal colic. Applying nanotechnology to plant extracts has revealed an advantageous strategy for herbal drugs considering the numerous features that nanostructured systems offer, including solubility, bioavailability, and pharmacological activity enhancement. The present study reports the preparation and characterization of chitosan-sodium tripolyphosphate nanoparticles (NPs) charged with A. chica standardized extract (AcE). Particle size and zeta potential were measured using a Zetasizer Nano ZS. The NP morphological characteristics were observed using scanning electron microscopy. Our studies indicated that the chitosan/sodium tripolyphosphate mass ratio of 5 and volume ratio of 10 were found to be the best condition to achieve the lowest NP sizes, with an average hydrodynamic diameter of 150±13 nm and a zeta potential of +45±2 mV. Particle size decreased with AcE addition (60±10.2 nm), suggesting an interaction between the extract's composition and polymers. The NP biocompatibility was evaluated using human skin fibroblasts. AcE-NP demonstrated capability of maintaining cell viability at the lowest concentrations tested, stimulating cell proliferation at higher concentrations. Antiulcerogenic activity of AcE-NP was also evaluated with an acute gastric ulcer experimental model induced by ethanol and indomethacin. NPs loaded with A. chica extract reduced the ulcerative lesion index using lower doses compared with the free extract, suggesting that extract encapsulation in chitosan NPs allowed for a dose reduction for a gastroprotective effect. The AcE encapsulation offers an approach for further application of the A. chica extract that could be considered a potential candidate for ulcer-healing pharmaceutical systems.103897-390

The role of spray-drying atmosphere on fridericia chica (bonpl.) L.G. Lohmann standardized extract production for wound healing activity

Fridericia chica (Bonpl.) L.G. Lohmann (synonym Arrabidaea chica Verlot) is widely used in Brazilian folk medicine. Considering overcoming pitfalls of scaling up production of plant extracts, herein the effects of N2 atmosphere for extract spray-drying process is reported. Samples were monitored by in vitro antioxidant activity and microbiological evaluation. The drying atmosphere influenced 3-deoxyanthocyanines content when using air as atomizing gas, decreasing carajurin (37.5%) content with concomitant increase in luteolin yield (24.1%). Both drying processes preserved the pharmacological activity. In the cell migration test with HaCaT cells, the extract dried under air flow (5 μg/mL) promoted wound closure by 78% (12 hours) whereas the extract dried using N2 flow promoted 49% (12 hours), with 98% closure (12 hours) for the positive control. The antimicrobial evaluation for Staphylococcus aureus did not differ within drying atmospheres, with MIC (minimum inhibitory concentration) at 0.39 mg/mL. Therefore, the drying process reported herein did not interfere with the biological activity’s outcome.The authors A.L.T.G.R.and M.A.F thank CNPq for research productivity fellowship. The authors also thank the Chemical, Biological, and Agricultural Pluridisciplinary Research Center (CPQBA/Unicamp) for the laboratory infrastructure. Sao Paulo Research Foundation (FAPESP). This work was supported by the Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil, Financing Code 001) and the National Council for Scientific and Technological Development (CNPq, Brazil, grant numbers # 132448/2016-5, # 132207/2017-6, # 429463/2018-9).Peer reviewe

Flavonoid-enriched plant-extract-loaded emulsion: a novel phytocosmetic sunscreen formulation with antioxidant properties

The aim of this study was to develop a phytocosmetic sunscreen emulsion with antioxidant effect, containing a blend of flavonoid-enriched plant extracts. In vitro sun protection factor, antioxidant activity, skin irritation, photostability, cutaneous permeation, and retention of flavonoids were evaluated. Thermodynamically stable emulsions were obtained and tested for sensorial analysis after loading the blend of extracts. The selected emulsion was stable when stored at low temperatures (5 C), for which after 120 days the concentration of quercetin and rutin were above their limit of quantification, i.e., 2.8 ± 0.39 µg/mL and 30.39 ± 0.39 µg/mL, respectively. Spreadability, low rupture strength and adhesiveness were shown to be similar to a conventional topical product. Higher brittleness, pseudo-plastic, and viscoelastic behaviors were also recorded for the developed phytocosmetic sunscreen. The product presented a critical wavelength of 387.0 nm and ultraviolet rays A and B (UVA/UVB) rate of 0.78, confirming that the developed formulation shows capacity for UVA/UVB protection, protecting skin against damages caused by Ultraviolet (UV) radiation. Rutin was shown to permeate the skin barrier and was also quantified in the stratum corneum (3.27 ± 1.92 µg/mL) by tape stripping and retention test (114.68 ± 8.70 µg/mL). The developed flavonoid-enriched phytocosmetic was shown to be non-irritant to skin by an in vitro assay. Our results confirm the antioxidant activity, sun protection, and physical properties of the developed phytocosmetic for topical application.This research was funded by FAPESP (grant number 2015/25533‐7 and 2017/14757‐7), CAPES and CNPq. The authors also received support from the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project reference M‐ERA‐NET/0004/2015‐PAIRED, co‐financed by FEDER, under the Partnership Agreement PT2020, and PhD scholarship (SFRH/BD/130555/2017).info:eu-repo/semantics/publishedVersio

Stability evaluation of dry extract and semi-solid formulations containing Arrabidaea chica Verlot for healing use

Orientador: Mary Ann FoglioDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: Arrabidaea chica (Humb. & Bonpl.) Verlot, popularmente conhecida como crajiru, espécie presente na lista de plantas medicinais de interesse ao SUS (Renisus) para o uso popular em enfermidades da pele. Estudos desenvolvidos no CPQBA-Unicamp comprovaram que o extrato bruto de A. chica possui ação cicatrizante induzindo a proliferação de fibroblastos in vitro, estimulando a síntese de colágeno in vivo e in vitro. Este estudo estabeleceu parâmetros para permitir a produção de um medicamento à base de A. chica em escala semi piloto, além de determinar condições adequadas de armazenamento, secagem e embalagem do produto final. Entre os compostos sensíveis à luz e à temperatura destaca-se a carajurina, que é responsável pela cor vermelha do extrato. A fim de aumentar a tempo de prateleira do produto microencapsulado por spray drying, utilizaram-se três materiais de parede: goma arábica (GA), goma de cajueiro (CG), e a mistura de goma arábica / maltodextrina (GM) na proporção de 1/1. Os diferentes materiais de parede apresentaram rendimentos de 82; 79 e 89,9% e teor de carajurina de 1,92%, 1 62% e 1,99%, respectivamente. Atividade antioxidante medida pelo método ORAC apresentou valores 1066,9, 1363,8 e 1026,2 uM TE / g. Os estudos de estabilidade foram realizados com extrato livre e microencapsulado armazenados em diferentes embalagens e condições. O produto armazenado a 40 ° C e 75% UR embalado em frascos de polietileno de alta densidade e saches cor de alumínio revestido de plástico diminuiu o teor de carajiruna em 10% em 20 dias de avaliação, enquanto que a embalagem de vidro foi mais estável nessas condições, diminuindo10% do conteúdo de carajiruna após 29 dias de teste. A maior meia-vida do produto microencapsulado foi de 160 dias, armazenado em saches e mantidos a 10 ° C. Todas as formulações semissólidas, avaliadas em modelos experimentais de cicatrização in vivo, foram capazes de reduzir entre 70 a 80% da área cutânea ulcerada em 10 dias de tratamento, contra 37% de redução do grupo controle no mesmo período. A estimulação da produção de colágeno para a formulação gel de Natrosol® contendo o extrato bruto livre foi de 0,093 ?g.mL-1, quando comparada com outras formulações de controle (0,019 ?g.mL-1) e bases (0,028 ?g.mL-1)Abstract: Arrabidaea chica (Humb. & Bonpl.) Verlot specie, popularly known as Crajiru, included in the National List of interest to SUS (Renisus) is reported to have healing properties for skin ailments. Studies conducted in CPQBA-UNICAMP showed that the crude extract of this plant species induced fibroblast proliferation in vitro, stimulating collagen synthesis in vivo and in vitro. This study established parameters to enable the production of an herbal medicine in semi pilot scale. The drying, storage and packaging conditions were evaluated to determine the best suited to the product. Among the compounds sensitive to light and temperature is carajurin, responsible for the extract's red color. In order to increase product's shelf half-life microencapsulation by spray drying using three different wall materials, arabic gum (GA), cashew gum (CG) and the mixture of arabic gum / maltodextrin (GM) the ratio of 1/1 were evaluated. The different wall materials provided 82.0, 79.0 and 89.9% yields respectively, with carajurin content of 1.92%, 1 62%, and 1.99%. Antioxidant activity measured by the ORAC method gave 1066.9, 1363.8 and 1026.2 ?M TE / g values. Stability studies were conducted with spray dried EB stored in different containers and conditions. The product stored at 40 ° C and 75% RH packed in high density polyethylene and sachets plastic coated aluminum color decreased 10% carajirun content throughout the 20 days period of evaluation. Whereas the glass container was more stable under these conditions, leading to10% decreases in carajirun content throughout 29 days. The greatest half-life of 160 days was verified when the product was stored in sachets at 10 ° C. The semi-solid formulations for topical use containing EB proposed in this study with Carbopol ¿ gel, Natrosol ¿ gel Cream A / O (free and microencapsulated), Cream O / A (free and microencapsulated), evaluated in experimental models of wound healing in vivo reduced 80-70% the ulcerated skin area after 10 days of treatment, whereas the control group decreased by 37%. Collagen concentration observed for the animals treated with Natrosol ¿ gel 2,5% A. chica was 0.093 ?g.mL-1, while animals treated with saline had collagen production of 0.019 ?g.mL-1 and Natrosol ¿ base gel concentration showed 0.028?g.mL-1MestradoFármacos, Medicamentos e Insumos para SaúdeMestra em Biociências e Tecnologia de Produtos Bioativo

Arrabidaea chica Verl : stablishment of drying and bioavailability parameters for development of mucoadhesive formulation

Orientador: Mary Ann FoglioTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Arrabidaea chica (Bonpl.) B. Verl. (Bignoniácea) é uma planta amplamente utilizada na medicina popular no Brasil. Este estudo relata a ação farmacológica de extratos padrão secos por atomização produzidos em escala industrial (Ar) e em escala laboratorial (N2), bem como sua viabilidade de produção. Os efeitos do uso de N2 e Ar como gases atomizadores no processo de secagem dos extratos foram comparados. O tipo de gás utilizado não alterou significativamente a cor. No entanto, o meio de secagem influenciou o teor de 3-desoxianocianinas presentes no extrato de A. chica, utilizando o ar como gás atomizador, apresentando redução da carajurina (37,5%) com aumento concomitante do teor de luteolina (24,1%). Ao avaliar os parâmetros do perfil químico por cromatografia líquida LC-MS / MS-ESI (+/-), sua atividade antioxidante in vitro, citotoxicidade e migração celular ambos os processos de secagem preservaram o perfil farmacológico das amostras. A atividade antioxidante também foi semelhante à IC50 (445,60 ± 12,73 e 466,99 ± 46,11). No teste de migração celular em células HaCat, observou-se que o extrato de folhas de A. chica secas com fluxo de ar (5 ?g / mL) promoveu fechamento da ferida em 78% (12 horas) e que as secas com fluxo de N2 levaram ao fechamento inferior, correspondente para 49% (12 horas), enquanto o controle positivo (meio RPMI com 5% soro fetal bovino) apresentou fechamento de 98% (12 horas). A avaliação antimicrobiana de Staphylococcus aureus dos extratos secos produziu efeito semelhante para ambos, com CIM (concentração inibitória mínima) a 0,39 mg / mL. A partir deste extrato padronizada de A. chica por spray drying foi desenvolvido uma formulação de filme mucoadesivo para uso na cavidade bucal. Os filmes foram preparados utilizando PVA (álcool polivinílico), sendo avaliadas as características físico-químicas, propriedades mecânicas e capacidade de mucoadesão. Estudos de citotoxicidade utilizando fibroblastos HGF-1 e queratinócitos HaCat também foram realizados. A atividade antioxidante e antifúngica dos filmes foi investigada contra diversas cepas de Candida. Os resultados mostraram a presença de nanopartículas de 200 a 300nm, potencial Zeta negativo (-11,13mV) apresentando PDI de 0,14, com atividade antioxidante DPPH IC50 393,37µg/mL, FRAP IC50 1,77µg/mL, superóxido IC50 104,9µg/mL; H2O2 IC50 394,8µg/mL e HOCl IC50 6,01µg/mL atividade antifúngica para diversas linhagens de Candidas na faixa de 14,5 a 58,5 µg/mL. A biodisponibilidade dos extratos brutos padronizados foi avaliada em ratos Spragle-Dawler. Os animais receberam tratamento oral com doses de 50mg/kg, dose única e 100mg/kg de extrato bruto de A. chica (EB), doses repetidas por sete dias. O teor de carajurina e luteolina foram avaliados no plasma por LC-MS-MS. Constatou-se a presença de luteolina intacta no plasma nos primeiros 15 minutos após a administração oral do extrato bruto padronizado, apresentando tempo de concentração máxima Tmáx aos 30 minutos e Cmáx 2,56ng/mL doses repetidas. A exposição plasmática de carajurina (antocianina), apresentou concentração plasmática abaixo do limite de quantificação do equipamento. As concentrações mais elevadas de carajurina detectada na urina demonstram que o extrato foi metabolizado e excretado. Portanto, o processo de secagem com fluxo de ar manteve as atividades biológicas do extrato de A. chica seco com N2. A. chica incorporadas no filme mucoadesivo não afetou a viabilidade das células HGF-1 e para as linhagens de HaCat, sendo adequado ao uso como cicatrizante bucal. Estes resultados são extremamente relevantes, pois constituem a primeira referência à absorção dos compostos antociânicos presentes na espécie A. chicaAbstract: Arrabidaea chica (Bonpl.) B. Verl. (Bignoniaceae) is a plant widely used in folk medicine in Brazil. This study reports the pharmacological action of spray-dried standard extracts produced on an industrial scale (Air) and laboratory scale (N2), as well as their viability of production. Effects of the use of N2 and Air as atomizing gases in the extracts drying process were compared. The type of gas used did not significantly alter post-dry color. However, the drying medium influenced the content of 3-deoxyanthocyanines present in A. chica extract using air as an atomizing gas, presenting a reduction of carajurin (37.5%) with a concomitant increase in luteolin content (24.1%). By evaluating the chemical profile parameters by liquid chromatography LC-MS/MS- ESI (+/-) mode, the in vitro antioxidant activity, cytotoxicity, and in vitro healing, both drying processes preserved the pharmacological profile of the samples. The antioxidant activity was also similar IC50 (445.60 ± 12.73 and 466.99 ± 46.11). In the cell migration test with HaCat cells, the extract dried with air flow (5 ?g/mL) promoted wound closure in 78% (12 hours) whereas that dried with N2 flow led to lower closure, corresponding to 49% (12 hours), and the positive control (Fetal Bovine Serum 5%) presented 98% closure (12 hours) compared to the negative control (Fetal Bovine Serum 0.2%). The antimicrobial evaluation for Staphylococcus aureus of the dry extracts yielded similar effect for both gases, with MIC (minimum inhibitory concentration) at 0.39 mg/mL Therefore, the drying process with air flow maintained the same biological activities as that dried with N2. A mucoadhesive film formulation was developed for use in the oral cavity from A. chica standardized extract dried by spray drying under N2. The films were prepared using PVA (polyvinyl alcohol), being evaluated the physicochemical characteristics, mechanical properties and mucoadhesion capacity. Cytotoxicity studies using HGF-1 fibroblasts and HaCat keratinocytes were also performed. The antioxidant and antifungal activity of the films was investigated against several Candida strains. The results showed the presence of 200 to 300nm nanoparticles, negative Zeta potential (-11.13mV) with 0.14 PDI, with antioxidant activity DPPH IC50 393.37µg / mL, FRAP IC50 1.77µg / mL, superoxide IC50 104 9µg / mL; H2O2 IC50 394.8µg / mL and HOCl IC50 6.01µg / mL antifungal activity for several Candidas strains in the range 14.5 to 58.5 µg / mL The standardized crude extracts were evaluated for bioavailability in Sprague Dawley rats. The animals received oral treatment with 50mg / kg doses, single dose and 100mg / kg of crude A. chica (EB)extract, repeated doses for seven days. Carajurin and luteoline content were evaluated in plasma by LC-MS-MS In which we found the presence of intact luteoline in plasma within the first 15 minutes after oral administration of the standardized crude extract, with a maximum Tmax concentration time of 30 minutes and Cmax 2.56ng / mL using repeated doses. Plasma exposure of carajurin (anthocyanin) is limited due to low oral bioavailability and extensive metabolism, with plasma concentration below the equipment quantitation limit. Higher concentrations of carajurin in the urine demonstrated that the extract was metabolized and excreted. Therefore, the airflow drying process maintained the same biological activities of the dried A. chica extract with N2. A. chica incorporated into the mucoadhesive film did not affect the viability of HGF-1 cells and HaCat strains, being suitable for use as oral healing. These results are extremely relevant as they constitute the first reference to the absorption of anthocyanin compounds present in A. chicaDoutoradoCiências BiomédicasDoutora em Ciências Médicas2015/08338-6FAPES