Assessing compatibility of excipients selected for a sustained release formulation of bilberry leaf extract

Abstract The study is aimed to assess the compatibility of bilberry leaf powder extract (BLPE) with six excipients selected for sustained-release (SR) tablet formulation. The BLPE was obtained with the addition of L-arginine and Myo-inositol as the carriers. Thermogravimetric (TG-DTG) analysis and Fourier-transform infrared spectroscopy (FTIR), supported by Pearson correlation analysis, were applied to detect possible interactions in the binary mixtures (1:1) of the BLPE with each excipient. The TG-DTG showed some deviations in the thermal behavior of the BLPE / excipient mixtures. However, only the thermal behavior of magnesium stearate in the mixture significantly differed from individual samples, which suggested chemical interaction for this excipient. The FTIR analysis confirmed that the BLPE is compatible with Eudragit L100, Methocel K4M, Methocel K100LV, Avicel PH-101, and Plasdone S-630. Whereas it undergoes solid-state chemical interaction in the binary mixture with magnesium stearate. According to the FTIR-spectra, it is suggested that this interaction results in the formation of stearic acid and alkalization of the medium. These findings evidence for the possibility of using TG-DTG analysis as an independent thermal technique for compatibility studies and also confirm the earlier reported interaction of basic lubricants, e.g., stearic salts, with active ingredients containing amino groups.

Dormancy of Floral Buds of Rabbiteye Blueberry in a Mild Winter Climate

Abstract Blueberry is an important fruit crop, with many health benefits. Despite its importance, much remains to be studied concerning the dormancy dynamics in rabbiteye cultivars growing in a mild winter climate. In this research, the dormancy in blueberry, rabbiteye cultivars 'Bluegem', 'Climax', 'Delite', and 'Powderblue', was studied in a mild winter region. The single-node cuttings biological test and the evaluation of the hydric status were performed in dormant winter reproductive buds. These experiments were performed during fall and winter in one year (2016). Moreover, chilling hours under or equal to 7.2 ºC were measured, and chill units were calculated according to Utah Model [1], Modified Utah Model [2], and Blueberry Model [3]. In conclusion, the four cultivars showed a similar pattern, revealing a dormant state in the initial sampling dates and a released dormancy in the final treatments, showing the decrease of dormancy in June and July. However, Delite was earlier than the other cultivars. Bluegem and Delite required 134.0 chilling hours, 127.0 chill units (Utah Model), 198.5 chill units (Modified Utah Model), and 971.5 chill units (Blueberry Model) for 50% of their green tip buds reach the opened bud stage. Climax required 44.0, -11.0, 56.5, and 440.5, respectively. And Powderblue required 44.0, 5.5, 77.0, and 725.0 respectively. This study can bring some insights into crop management and production of this important fruit crop, especially in a global climate-changing scenario, related to flowering and dormancy control, as well as helping to select suitable cultivars to a region, concerning chilling requirements.

The role of vaccinium myrtillus in the prevention of renal injury in an experimental model of ruptured abdominal aortic aneurysm

Abstract Objective: To examine the biochemical and histopathological renal effects of ischemia/reperfusion (I/R) injury using a ruptured abdominal aortic aneurysm (RAAA) model in rats and to investigate the potential protective effects of whortleberry (Vaccinium myrtillus). Methods: Thirty-two male Sprague-Dawley rats were randomly assigned into four groups - control, sham (I/R+glycerol), I/R, and I/R+whortleberry. Midline laparotomy alone was performed in the control group. Atraumatic abdominal clamps were attached under anesthesia to the abdominal aorta beneath the level of the renal artery in the groups subjected to I/R. Sixty-minute reperfusion was established one hour after ischemia. The sham group received five intraperitoneal doses of glycerol five days before I/R. The I/R+whortleberry group received a single intraperitoneal 50 mg/kg dose diluted with saline solution five days before I/R. All animals were finally euthanized by cervical dislocation following 60-min reperfusion. Results: Increases were observed in malondialdehyde (MDA) levels and tubular necrosis scores (TNS) in thin kidney tissues and in numbers of apoptotic renal tubule cells, together with a decrease in glutathione (GSH) levels, in sham and I/R groups. In contrast, we observed a decrease in MDA levels, TNS, and numbers of apoptotic renal tubule cells, and an increase in GSH levels with whortleberry treatment compared to the I/R group. Conclusion: Our findings suggest that whortleberry may be effective against acute kidney injury by reducing oxidative stress and apoptosis.

Infestation index of Drosophila suzukii (Diptera: Drosophilidae) in small fruit in southern Brazil / Índice de infestação de Drosophila suzukii (Diptera: Drosophilidae) em pequenas frutas no sul do Brasil

The spotted-wing drosophila, Drosophila suzukii Matsumura, is considered the main insect pest of small fruit in the world. Identifying susceptible hosts is essential to develop management strategies. The aim of this study was to verify the level of D. suzukii infestation in blackberry, blueberry, strawberry, cattley guava and Surinam cherry fruits cultivated in the southern region in Brazil, and to determine the infestation index (II) per fruit. The studies were carried out during two harvests (2015/16 and 2016/17) in three areas with organic cultivation of small fruit. The highest level of D. suzukii natural infestation was observed in blackberry (40 to 65% infestation), and strawberry (approximately 30% infestation) fruits. In contrast, blueberries were less preferred (< 7% infestation). For native fruit of the region (cattley guava and Surinam cherry), it was also verified infestation of the fly, demonstrating they are hosts for multiplication in the off-season periods of the other crops. In relation to II, blackberry and Surinam cherry provided a higher average number of insects per gram of fruit (≈ 1.6 adults of D. suzukii). In contrast, blueberries and cattley guava had the lowest insect ratio per gram of fruit (≈ 0.7 adults per gram). The period between late spring to mid-autumn was considered ideal for the pest occurrence in the field. The knowledge of natural infestation levels is essential for understanding the behavior of the pest in the field, which will assist in the design of management strategies.(AU)

A drosófila-da-asa-manchada, Drosophila suzukii Matsumura, é considerada o principal inseto-praga de pequenos frutos no mundo. A identificação de hospedeiros suscetíveis é essencial para o desenvolvimento de estratégias de manejo. O objetivo deste estudo foi verificar o nível de infestação de D. suzukii em frutos de amoreira-preta, mirtileiro, morangueiro, araçazeiro e pitangueira cultivados na região no sul do Brasil e determinar os índices de infestação (II) por fruto. Os estudos foram realizados durante duas safras (2015/16 e 2016/17) em três áreas com cultivo orgânico de pequenas frutas. O maior nível de infestação natural de D. suzukii foi observado em amora-preta (40 a 65% de infestação) e morango (aproximadamente 30% de infestação). Em contraste, o mirtilo foi menos preferido (< 7% de infestação). Para as frutas nativas da região (araçá e pitanga), também ocorreu infestação da mosca, demonstrando serem hospedeiros potenciais para a multiplicação da praga nos períodos de entressafras. Em relação ao II, amoras e pitangas proporcionaram um maior número médio de insetos por grama de fruto (≈ 1,6 adultos de D. suzukii). Por outro lado, mirtilos e araçás apresentaram a menor relação de insetos emergidos por gramas de frutos (≈ 0,7 adultos por grama). O período entre final da primavera até meados do outono foi considerado ideal para a ocorrência da praga no campo. O conhecimento dos níveis de infestação natural é fundamental para o entendimento do comportamento da praga no campo, o que auxiliará no delineamento de estratégias de manejo.(AU)

Fotoprotetores bioativos contendo extrato de mirtilo (Vaccinium myrtillus L. ): caracterização físico-química e funcional / Bioactive sunscreens containing blueberry (Vaccinium myrtillus L. ): physicochemical and funcional characterization

Os efeitos deletérios causados pela radiação ultravioleta (UV) e o aumento significativo no diagnóstico de câncer de pele, confirmam a necessidade de um progresso significativo na pesquisa de produtos fotoprotetores eficazes e seguros, para proteção eficaz da pele. As formulações atuais associam filtros UV, orgânicos e inorgânicos, com eficácia limitada e que podem acarretar reações cutâneas adversas. O extrato de Vaccinium myrtillus L. (EVM) apresenta em sua composição compostos fenólicos, como as antocianinas, que possuem atividade antioxidante. O objetivo deste estudo foi avaliar formulações fotoprotetoras contendo extrato de Vaccinium myrtillus L. com amplo espectro de ação e concentrações reduzidas de filtros UV. As emulsões contendo ou não EVM e filtros orgânicos (octocrileno e metileno bis-benzotriazolil tetrametilbutilfenol) e inorgânico (dióxido de titânio) foram avaliadas e consideradas estáveis perante parâmetros pré-definidos. O perfil de segurança foi determinado pelo método in vitro Hen´s Egg Test - Chorioallantoic Membrane (HET-CAM) e o potencial antirradicalar do EVM foi confirmado pelo teste de DPPH• A formulação fotoprotetora acrescida de 5,0% de EVM foi avaliada quanto à eficácia fotoprotetora in vivo e in vitro e não demonstrou aumento significativo no FPS quando comparada à formulação que continha somente os filtros solares e, no ensaio referente à hidratação da pele, não houve alteração nos dados, segundo teste de eficácia clínica. Os resultados obtidos sugeriram que mesmo não apresentando aumento no valor de FPS in vivo, a formulação fotoprotetora contendo o extrato, poderia atuar como agente antioxidante evitando os danos provocados pela radiação UV

The deleterious effects caused by ultraviolet radiation (UV) and the significant increase in the diagnosis of skin cancer confirm the need for significant progress in researching effective and safe sunscreen products for effective skin protection. Current formulations associate UV, organic and inorganic filters with limited efficacy that can lead to adverse skin reactions. Vaccinium myrtillus extract (EVM) contains in its composition polyphenols compounds, such as anthocyanins, which have been antioxidant activity. The objective of this study was to evaluate sunscreens containing EVM with broad action spectrum and reduced concentrations of UV filters. Emulsions containing or not EVM and organic (octocrylene and methylene bis-benzotriazolyl tetramethylbutylphenol) and inorganic (titanium dioxide) filters were evaluated and considered stable under pre-defined parameters. The safety of the emulsion was assessed was determined by the in vitro Hen´s Egg Test - Chorioallantoic Membrane method (HET-CAM) and the antiradical potential of EVM was confirmed by the DPPH• test. The sunscreen formulation containing EVM 5.0% was photoprotective efficacy evaluated in vivo and in vitro and did not show a significant increase in SPF when compared the formulation only with UV filters and no improves skin hydration, according to clinical efficacy assay. The results of the study suggest that even without increase SPF in vivo, the sunscreen formulation containing the extract may show antioxidant activity avoiding damage caused by UV

Registro de Cyclocephala flavipennis Arrow, 1914 (Coleoptera: melolonthidae) danificando plantas de mirtileiro no Brasil / Record of Cyclocephala flavipennis Arrow, 1914 (Coleoptera: Melolonthidae) injuring blueberry plants in Brazil

Larvas de Cyclocephala flavipennis Arrow, 1914, são comumente encontradas em cereais de inverno (trigo, cevada, aveia e triticale), milho e soja, no Rio Grande do Sul. Em março de 2012, larvas desta espécie foram detectadas em plantas de mirtileiro (Vaccinium ashei Reade), cultivar 'O´Neal', no município de Pelotas, RS. Os insetos alimentaram-se de raízes em áreas restritas do pomar. Este é o primeiro relato da ocorrência do coró-pequeno, C. flavipennis, em plantas de mirtileiro.

Cyclocephala flavipennis Arrow, 1914 are usually found in winter cereals (wheat, barley, oat and triticale), corn and soybean in Rio Grande do Sul, Brazil. Larvae of the species were detected in blueberry (Vaccinium ashei Reade) cultivar 'O´Neal', in March 2012 in the city of Pelotas, RS, Brazil. The white grub fed up with roots in restricted areas from the orchard. This is the first record of C. flavipennis in blueberry plants.

Effects of Bilberry on Deoxyribonucleic Acid Damage and Oxidant-Antioxidant Balance in the Lens, Induced by Ultraviolet Radiation

Background: This study investigated the possible protective effects of bilberry extract after exposing rat eyes to ultraviolet-B (UV-B) radiation. Methods: Four groups of rats were included in this study, each consisting of 10 Wistar rats. The first group acted as the control, and the second group was exposed to UV-B, 5 KJ/m2 (λm = 300 nm), for 15 minutes. The third group was orally administered bilberry extract (160 mg twice per day) for two weeks before exposure to the UV-B, while the fourth group was administered the same dose of bilberry extract for two weeks before euthanisation. A comet assay was used to examine DNA damage, while the malondialdehyde (MDA) level and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), activities were measured in the lens. Results: After exposing the rats to UV-B radiation, the mean percentage tail DNA and tail moment were significantly increased (P < 0.001) when compared to the control group. In the same context, the lens tissue MDA levels and CAT activity were also significantly increased (P < 0.001). The supplementation of the bilberry extract was found to improve the comet assay parameters and enzymatic activity of the rat lens tissue. Conclusion: The administration of bilberry led to a decrease in the oxidative stress in the lens tissues and DNA damage induced by UV-B radiation in the lenses of Wistar rats.

The Efficacy of Vaccinium Uliginosum for Early Age-Related Macula Degeneration

PURPOSE: To evaluate the effect of Bog Bilberry (Vaccinium uliginosum) extract in eyes with early age-related macular degeneration (AMD). METHODS: Forty-four eyes of forty four patients with early AMD were included in this randomized, double-blinded, and placebo-controlled study. All participants were randomly assigned to either the placebo group (n = 24), or the bog bilberry extract group (n = 20). Before drug administration, an ophthalmic examination which included slit lamp microscopy, best corrected visual acuity, and intraocular pressure was performed, and repeated 1and 3 months after treatment. Objective scatter index, glare and tear film break-up time were checked by Optical Quality Analysis System (OQAS, Visiometrics, Spain) and drusen volume, central macular thickness, and RPE and IS/OS junction thickness were investigated with spectral-domain optical coherence tomography (Spectralis, Heidelberg, Germany). RESULTS: In the bog bilberry extract group, RPE and IS/OS junction thickness was significantly increased compared to the placebo group after 3 months of drug administration. CONCLUSIONS: Bog Bilberry extract may play a favorable role in preventing the atrophic change of RPE and IS/OS junction layer and the progression of early macular degeneration.

Alternative therapy in glaucoma management: Is there any role.

Glaucoma is one of the leading causes of blindness worldwide. Various randomized controlled clinical trials have shown that lowering intraocular pressure (IOP) does reduce progression of primary open-angle glaucoma. However, there is lots of interest in nonpharmacological options that includes lifestyle adjustment and alternative and complementary therapy (ACT). At least 5% glaucoma population uses ACT. Various lifestyle activities like exercise and alcohol can reduce IOP by 1 to 2 mm Hg but would have small effect on glaucoma. The psychological stress can increase IOP. Hypothetically and few studies do show neuroprotective effect (or effect on ocular blood flow) of alcohol, Gingko biloba, bilberry, but the current evidence is weak for its routine use. We must also remember the side effects of ‘medications’ (e.g., marijuana, alcohol) before promoting as remedy for glaucoma. In current armamentarium of glaucoma management, ACT cannot substitute the conventional treatment available to lower IOP.

Extração alcoólica de fenólicos e flavonóides totais de mirtilo Rabbiteye (Vaccinium ashei) e sua atividade antioxidante / Alcoholic extracts of total phenolics and flavonoids from rabbiteye blueberry (Vaccinium ashei) and their antioxidant activity

Uma infinidade de produtos de cosmetologia tem utilizado mirtilo, uma pequena fruta com inúmeras alegações de propriedades biológicas, na formulação de uma variedade de produtos como cremes hidratantes, esfoliantes, protetores da radiação ultravioleta, entre outros. Neste sentido, a composição química desta pequena fruta é associada a estas propriedades biológicas,no entanto, poucos relatos científicos são encontrados na literatura. Desta forma, o presente estudo avaliou os teores de compostos fenólicos e de flavonóides, bem como a relação destes compostos com a atividade antioxidante de extratos hidroalcoólicos preparados a partir de frutas de mirtilo cv. "Rabbiteye" (Vacciniumashei). Diferentes proporções de álcool (etanol ou metanol) em água deionizada (ou seja, 40:60, 60:40 e 80:20 (v/v)) foram avaliados quanto à capacidade de extração de fenólicos totais e de flavonóides de amostras de mirtilo em duas condições: frescas (frutas in natura)e secas (após secagem a 105ºC por 15 h). Todas as extrações alcoólicas foram realizadas à temperatura ambiente e sob agitação. Dentre as proporções utilizadas para a extração dos compostos fenólicos foi verificado que, em geral, a mistura metanol/água 80:20(v/v) e a mistura etanol/água 60:40 (v/v) foram os que apresentaram maiores teores de fenólicos e flavonoides totais, e que houve uma correlação positiva forte entre as concentrações de fenólicos e de flavonóides com a atividade antioxidante daqueles extratos hidroalcoólicos de mirtilo, segundo análise do coeficiente de correlação de Pearson.

A wide range of cosmetic products, including moisturizers, exfoliating scrubs and sunscreens, have been formulated with blueberry, a small fruit within numerable claims to biological properties. Although the chemical composition of these fruits has been associated with these biological properties, few studies can be found in the literature. In the present study, the phenolic and flavonoid contents of hydroalcoholic extracts of the rabbiteye blueberry (Vaccinium ashei)were analyzed and the correlation of these compounds with the antioxidant activity of the extracts investigated (by Pearson's correlation coefficient). Various mixtures of alcohol (ethanol or methanol) with deionized water (40:60, 60:40 and 80:20 (v/v)) were tested for their capacity to extract phenolics and flavonoids from blueberries in two conditions: fresh (as picked) and dried (at 105ºC for 15 h). All the extractions were carried out at room temperature with shaking. Out of all the solvent mixtures used for the extractions it was found that, in general, the 80:20 (v/v) methanol/water and 60:40 (v/v) ethanol/water mixtures showed the highest phenolic and flavonoid contents, respectively, with a strong positive correlation between the phenolic and flavonoid contents of the blueberry hydroalcoholic extracts and their antioxidant activity.

Clinical Evaluation of Patients with Nonproliferative Diabetic Retinopathy Following Medication of Anthocyanoside: Multicenter Study

PURPOSE: To prospectively investigate the change of clinical manifestations after 1 year of administration of anthocyanoside (Tagen-F(R)) to patients with NPDR-associated macular edema. METHODS: One hundred seventy-five eyes in 88 patients were enrolled in this study, at 5 centers, from March, 2005 to October, 2005. Patients took 3 capsules of Vaccinium myrtillus extract (170 mg/capsule, Tagen-F(R), Kukje pharmaceutical) per day. The primary endpoints were corrected visual acuity and contrast sensitivity which were checked at 2 months following the beginning of treatment [East 1]. The secondary endpoints were the number of hard exudates, microaneurysms, leaking points and the changes of foveal thickness. These were examined at the beginning of, 6 months after, and 12 months after treatment. RESULTS: Corrected visual acuity showed no significant changes during 12 months. Contrast sensitivity improved gradually, especially in 12, 16 cycles per degree [East 2]. There was no statistically significant changes in the numbers of hard exudates, microaneurysms, and leaking points. Foveal thickness measured by OCT was maintained and there was no aggravation of macular edema. CONCLUSIONS: There was marked improvement of contrast sensitivity in patients with NPDR after 1 year of administration of anthocyanoside (Tagen-F(R)), and it might contribute to the quality of vision and the satisfaction of patients. Visual acuity and macular edema were maintained without aggravation.