Launching a CDMO in Brazil aiming to develop biopharmaceuticals for clinical trials

The innovation timeline is expensive, risky, competitive, time-consuming, and labor-intensive. In order to overcome such challenges and optimize financial resources, pharmaceutical companies nowadays hire contract development and manufacturing organizations (CDMO) to help them. Based on the experience acquired first from the development of two biopharmaceuticals, the Heterologous Fibrin Sealant and the Apilic Antivenom, and more recently, during their respective clinical trials; the Center for the Study of Venoms and Venomous Animals (CEVAP) proposed to the Ministry of Health the creation of the first Brazilian CDMO. This groundbreaking venture will assist in converting a candidate molecule - from its discovery, proof of concept, product development, up to pilot batch production - into a product. The CDMO impact and legacy will be immense, offering service provision to the public and private sector by producing validated samples for clinical trials and academic training on translational research for those seeking a position in pharmaceutical industries and manufacturing platforms.(AU)

Pretreatment with water kefir reduces the development of acidified ethanol-induced gastric ulcers

Abstract To evaluate the gastroprotective and antioxidant effects of pretreatment with water kefir on ulcers induced with HCl/ethanol. All pretreatments lasted 14 days. Male mice were separated into five groups: the control (C) group received vehicle without ulcer induction; the ulcerated (U) group received vehicle; the lansoprazole (L) group received 30 mg/kg/day lansoprazole; the water kefir (WK15 and WK30) groups received WK at a dose of 0.15 or 0.30 ml/kg/day, respectively. Gastroprotection was measured by ulcer area, ulcer index and ulcer reduction percentage. Antioxidant effects were quantified by measuring advanced oxidized protein products (AOPPs), superoxide dismutase (SOD), and catalase activity in the stomach. Pretreatment with WK at both doses promoted gastroprotection against HCl/ethanol-induced ulcers much like the pretreatment with lansoprazole. In addition, WK decreased protein oxidation while increasing SOD and catalase activity. We concluded that pretreatment with water kefir increases the activity of antioxidant enzymes, preventing gastric lesions induced by HCl/ethanol by maintaining the antioxidant performance in gastric tissue.

Decline in Public Spending on Biopharmaceutics in Brazil

Abstract Biopharmaceuticals, mainly monoclonal antibodies, and fusion proteins are drugs that have gained notoriety in the treatment of various chronic and inflammatory diseases and have high prices. The study aimed to verify which monoclonal antibodies and fusion proteins were most incorporated into the Unified Health System (SUS), which therapeutic indication most benefited from them and to analyze public spending on these biopharmaceuticals from January 2012 to September 2019. This study performed a qualitative and quantitative analysis of biopharmaceuticals incorporated by SUS. The data were collected on the websites of CONITEC and the Health Price Bank. The results demonstrated that subcutaneous adalimumab was most frequently incorporated, and the most requested therapeutic indication was rheumatoid arthritis. Public spending on biopharmaceuticals exceeded R$ 28 billion (more than US$ 140 billion). However, a downward trend was confirmed (-266.7%) in the period evaluated. Despite the increase in demand and public spending on biologics in general, in Brazil and worldwide, the results of this research show that there was a drop in public spending on the biopharmaceuticals studied in the last seven years.

Thrombolysis, clotting, and genotoxic activities modulated by essential oils extracted from Lippia alba

Abstract The composition and pharmacological properties of Lippia alba (Mill.) (L. alba) (Verbenaceae) flower and leaf essential oils (EO) were determined in this study. The major constituents in the flower EO were geranial (49.83%) and neral (32.75%), and in the leaf EO were geranial (38.06%), neral (31.02%), and limonene (18.03%). Flower EO inhibited thrombolysis induced by Bothrops moojeni (B. moojeni) and Lachesis muta muta (L. muta muta) venoms (0.05-1.2 µL mL-1). When tested against L. muta muta venom, the protective effect was smaller in both EO. The EOs prolonged the clotting time induced by L. muta muta venom and a procoagulant effect was observed on B. moojeni. In the comet assay, the flower EO presented anti-genotoxic action (damage frequency of only 11.6 - 34.9%) against the L. muta muta venom. The positive control (Doxorubicin) and the venom alone presented a damage frequency of 80.3% and 70.7%, respectively. The flower EO protected DNA from damage induced by L. muta muta venom. L. alba leaf and flower EOs presented anti-genotoxic action

Synthesis and Biological Activity of Trolox Amide Derivatives

Abstract A series of Trolox amide derivatives were synthesized by modifying the carboxyl groups of Trolox. Thirty target compounds were obtained and characterized through nuclear magnetic resonance and mass spectrometry. Trolox derivatives were employed to explore the potential structure-antioxidant activity relationships. The antioxidant activities of these compounds were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP) and hydroxyl radical assays. DPPH scavenging activity test results illustrated that compounds exhibited scavenging activities similar to L-ascorbic acid and Trolox, with compounds 14a, 18a, 24a and 26a in particular exhibiting higher scavenging activities than L-ascorbic acid. The results demonstrated that compounds displayed ABTS scavenging activities similar to L-ascorbic acid and Trolox, with compounds 26a and 29a in particular having potency twofold higher. FRAP assay results indicated that compounds 11a, 19a, 25a, 29a and 30a had activity similar to Trolox. The results revealed that compounds 6a and 19a had similarly high hydroxyl radical-scavenging activities as Trolox. The results of α-glucosidase experiments uncovered that compounds 10a, 25a, 28a and 29a had excellent inhibitory activity, which was similar to that of acarbose and different from Trolox. The results of acetylcholinesterase and butyrylcholinesterase experiments demonstrated that some compounds had weak anticholinesterase activities. 26a and 29a are important Trolox derivatives with better biological activity profiles and deserve further study

The study of the biological activities of Ziziphora clinopodioides

Abstract The aim of the current study was to determine the chemical constituents of essential oil and to study the antibacterial and antioxidant activities of essential oil and the extracts obtained from the raw material of Ziziphora wild growing in the floras of Armenia and Artsakh cultivated in the hydroponic conditions. The essential oils were obtained by the method of hydro-distillation. The determination of the essential oil constituents were performed by the GC-MS method. Agar disk diffusion method was used to study the antimicrobial activity of essential oils. The antioxidant activity determination was carried out DPPH test by the spectrophotometric method, at the same time IC50 was determined. The highest values of the essential oils yield (1.25 ± 0.01%) and IC50 13.83±0.218(x10-5)g/l) were received for the plant cultivated in hydroponic conditions. For the first time in the above studied samples, by the method of GC-MS more than 70 components were revealed. The results of the study showed that essential oils of Ziziphora exhibit antimicrobial activity and the extracts revealed relatively expressed antioxidant activity. The study results show the future prospects of the use of Ziziphora not only as the source of flavonoids and essential oils, but also antimicrobial and antioxidant agents.

Chemical and biological properties of nordihydroguaiaretic acid

Nordihydroguaiaretic acid (NDGA) is a natural product obtained by the alkaline extraction of dried plants of Larrea tridentata species. Due to the biological properties presented, such as antioxidant, anti-inflammatory, antiviral and cytotoxic capacity, this compound is being increasingly studied. In this review, it was evaluated the benefits of NDGA against different animal models. Besides that, it was found that this compound has antitumor activity similar to its synthetic derivative terameprocol in prostate tumors. The hypoglycemic effect may be evidenced by the inhibition of sugar uptake by NDGA; in obesity, studies have observed that NDGA presented a positive regulatory effect for Peroxisome proliferator-activated receptors (PPAR-α) involved in the oxidation of hepatic fatty acids and reduced the expression of lipogenic genes. Regarding its antioxidant potential, its mechanism is related to the ability to in vitro scavenging reactive substances. Although there are several studies demonstrating the benefits of using NDGA, there are also reports of its toxicity, mainly of liver damage and nephrotoxicity

Antioxidant activity and hypoglycemic effect assessment of the leaves from Syzygium cumini (L. ) Skeels in Wistar rats

Syzygiumcumini(L.) Skeels wasadaptedto the climatic conditionsandsoil typesin Brazil. Its fruits, leaves andinner barkare usedin folk medicinedue to their highantioxidant, anti-inflammatory, anticarcinogenicandantidiabeticactivities mainlyassociated with the presenceof phenolic compounds. It is estimated thatat least300million peopleworldwide developdiabetesand approximately 11million peopleare carriersof the disease in Brazil.The objectiveof this workwas to evaluate thein vitro antioxidant activity, as well as thehypoglycemic actionofhydroethanolic extract(HEE), the ethyl acetate(EAF) andhydromethanolic(HMF) fractions from leavesofS.cumini(L.) Skeels in rats. All assays werecarried out in three replications. Data wereexpressed as meanSDand significance was evaluated by ANOVAand Bonferronitest (p < 0.05). The results indicatea significant(p < 0.05) total phenolcontent (207 ± 2.3GAE mg g-1) andantioxidant activity(EC50=9.05±0.170 µg mL-1) for EAF. HEE and its fractions showed no significant (p > 0.05) actionto modulateglucosebytheOGTT assayinnondiabetic micecompared to control. Thus the use of the plant against diabetes in individuals is not proven.

Análise Técnico-Econômica para a produção de biofármacos de L-asparaginase / Technical-Economic analysis for the production of L-asparaginase biopharmaceuticals

A enzima L-asparaginase é comumente utilizada como biofármaco para o tratamento da Leucemia Linfoblástica Aguda e possui altas taxas de cura com o medicamento disponível no mercado. Atualmente a aquisição deste biofármaco é fruto integral de importação, não sendo realizada produção nacional, muito embora existam grupos de pesquisas nacionais que trabalham em pesquisas e no desenvolvimento de biofármacos alternativos da L-asparaginase. Assim, a presente dissertação tem como objetivo realizar análises técnico-econômicas para avaliar a viabilidade de implementação industrial de bioprocessos para a produção da L-asparaginase do tipo Erwinase PEGuilada e não PEGuilada, que foram previamente desenvolvidos na FCF-USP. As análises técnico-econômicas foram conduzidas por meio do software SuperPro Design® (Intelligen, Inc.) e permitiram adaptar o processo laboratorial para um processo piloto e possibilitaram estimar os valores de custo de produção unitário (Unity Cost of Production - UPC) de US$ 12,37/mg e US$ 3,46/mg para a L-asparaginase monoPEGuilada e nativa obtida por processo similar, respectivamente. O custo unitário de produção para a enzima peguilada foi, portanto, estimado em cerca de 4 vezes o mesmo custo para a produção da enzima peguilada, sendo tal aumento de custo devido às operações de peguilação, já que ambas as plantas foram mantidas nas mesmas dimensões. Ainda, foram obtidos indicadores econômicos, que indicam a atratividade do processo desenvolvido, muito embora tenham sido identificados diversos gargalos de processo e fatores a serem otimizados e melhorados de forma a tornar o processo mais atrativo sob os pontos de vista técnico e econômico. Em uma análise de sensibilidade preliminar um aumento factível da densidade celular já mostra que é possível reduzir em mais de 30% o UPC. De toda forma, ainda que não otimizado, o processo apresentou valores e dados compatíveis com os biofármacos de L-asparaginase já disponíveis no mercado

The enzyme L-asparaginase is commonly used as a biopharmaceutical in the treatment of Acute Lymphoblastic Leukemia, presenting high cure rates with the formulations available on the market. Nowadays, the acquisition of this biopharmaceutical is only from importation, given that there is no national production being carried out, although there are national research groups working on research and development of alternative L-asparaginase biopharmaceuticals. Thus, this project aims at carrying out technical-economic analyzes to evaluate the viability of industrial implementation of bioprocesses for the production of L-asparaginase of the PEGylated and non-PEGylated Erwinase type previously developed at FCF-USP. The technical-economic analyzes, conducted by means of the software SuperPro Design® (Intelligen, Inc.), allowed to adapt the laboratory process to a pilot process and made it possible to estimate the unit cost of production (UPC) values of US $ 12.37 / mg and US $ 3.56 / mg for monoPEGylated L-asparaginase and bare obtained by similar process, respectively. The unit cost of production for the pegylated enzyme was, therefore, estimated at about 4 times the same cost for the production of the pegylated enzyme, such an increase in cost due to pegylation operations, since both plants were maintained in the same dimensions. Moreover, economic indicators were obtained, which indicate the attractiveness of the developed process. However, several process bottlenecks and factors to be optimized and improved were identified to make the process more attractive from the technical and economic point of view. In a preliminary sensitivity analysis, a feasible increase in cell density already shows that it is possible to reduce UPC by more than 30%. Accordingly, although not optimized, the process presented values and data compatible with the L-asparaginase biopharmaceuticals already available on the market

Evaluación de la calidad microbiológica de productos naturales procesados de uso medicinal comercializados en Quito, Ecuador / Evaluation of the microbiological quality of natural processed products for medicinal use marketed in Quito, Ecuador

RESUMEN Objetivos: Determinar la calidad microbiológica de una muestra de productos naturales procesados de uso medicinal de libre comercio en Quito, Ecuador. Materiales y métodos: 83 productos se sometieron a recuentos de microorganismos aerobios, mohos y levaduras por técnicas convencionales estandarizadas, de acuerdo a la Farmacopea de los Estados Unidos (USP, por sus siglas en inglés). Se identificaron los microorganismos presentes y se determinó su sensibilidad antimicrobiana usando el método de difusión en agar. Resultados: El 17,0% de los jarabes, el 27,0% de los productos tópicos y el 43,0% de los sólidos orales excedieron los límites especificados para el recuento total de microorganismos aerobios, mientras que el 33,0% de los jarabes, el 7,0% de los productos tópicos y el 36,0% de los sólidos orales excedieron el límite para mohos y levaduras. Los productos de uso ocular no pasaron la prueba de esterilidad. El género bacteriano más frecuentemente aislado fue Bacillus, seguido por Escherichia coli, Klebsiella y Enterobacter. Salmonella ni Staphylococcus aureus se encontraron en ningún producto, pero microorganismos potencialmente patógenos como Pseudomonas se aislaron en el 40,0% de los colirios. Enterobacter y Escherichia coli mostraron resistencia a múltiples compuestos y Pseudomonas no fue resistente a ningún antibiótico. Conclusiones: La calidad microbiológica de los productos examinados no fue adecuada. Se aislaron microorganismos potencialmente patógenos y resistentes a antibióticos. Estos productos podrían no ser aptos para su distribución y consumo, aun cuando muchos de ellos cuenten con registro sanitario. El control y regulación por los entes responsables es indispensable.

ABSTRACT Objectives: To determine the microbiological quality of samples from processed natural products used for medicinal purposes and marketed in Quito, Ecuador. Materials and methods: Aerobic microorganisms, molds and yeasts were counted by conventional standardized techniques, according to the United States Pharmacopoeia (USP), in samples from 83 products. The microorganisms found were identified and their antimicrobial sensitivity was determined using the agar diffusion method. Results: The total aerobic microorganism count exceeded the specified limits in 17.0% of syrups, 27.0% of topical products and 43.0% of oral solids; the molds and yeasts count exceeded the limit in 33.0% of syrups, 7.0% of topical products and 36.0% of oral solids. Products for eye use did not pass the sterility test. The most frequently isolated bacterial genus was Bacillus, followed by Escherichia coli, Klebsiella and Enterobacter. Salmonella and Staphylococcus aureus were not found in any product, but potentially pathogenic microorganisms such as Pseudomonas were isolated in 40.0% of the eye drops. Enterobacter and Escherichia coli showed resistance to multiple compounds and Pseudomonas was not resistant to any antibiotic. Conclusions: The microbiological quality of the products examined was not adequate. Potentially pathogenic and antibiotic resistant microorganisms were isolated from the samples. These products may not be suitable for distribution and consumption, even though many of them have sanitary registration. Control and regulation by the corresponding authorities is essential.

Strategies towards expansion of chemical space of natural product-based compounds to enable drug discovery

Natural products (NPs) are an excellent source of biologically active molecules that provide many biologically biased features that enable innovative designing of synthetic compounds. NPs are characterized by high content of sp3-hybridized carbon atoms; oxygen; spiro, bridged, and linked systems; and stereogenic centers, with high structural diversity. To date, several approaches have been implemented for mapping and navigating into the chemical space of NPs to explore the different aspects of chemical space. The approaches providing novel opportunities to synthesize NP-inspired compound libraries involve NP-based fragments and ring distortion strategies. These methodologies allow access to areas of chemical space that are less explored, and consequently help to overcome the limitations in the use of NPs in drug discovery, such as lack of accessibility and synthetic intractability. In this review, we describe how NPs have recently been used as a platform for the development of diverse compounds with high structural and stereochemical complexity. In addition, we show developed strategies aiming to reengineer NPs toward the expansion of NP-based chemical space by fragment-based approaches and chemical degradation to yield novel compounds to enable drug discovery

Reação tipo corpo estranho a preenchimento facial com poliamida / Foreign body reaction to polyamide filling in the face

O uso de substâncias para preenchimento dérmico é crescente, e o número de complicações devido à sua utilização, significativo. Neste trabalho, relatamos um caso de granulomas de corpo estranho após preenchimento facial com gel de poliamida, chamado AqualiftTM, produto não encontrável nas bases de dados da literatura científica. São discutidos aspectos clínicos, terapêuticos e histopatológicos. Faz-se uma advertência relativa ao uso desta substância.

Dermal fillers are increasingly used, and the number of complications due to their use is significant. In this work, we report the case of foreign body granulomas due to the facial injection of a polyamide gel, named AqualiftTM, a product not found in scientific literature databases. Clinical, therapeutic and hystopathological aspects are discussed. A warning is made, concerning the use of this substance.

Halotolerant bacteria in the São Paulo Zoo composting process and their hydrolases and bioproducts

Halophilic microorganisms are able to grow in the presence of salt and are also excellent source of enzymes and biotechnological products, such as exopolysaccharides (EPSs) and polyhydroxyalkanoates (PHAs). Salt-tolerant bacteria were screened in the Organic Composting Production Unit (OCPU) of São Paulo Zoological Park Foundation, which processes 4 ton/day of organic residues including plant matter from the Atlantic Rain Forest, animal manure and carcasses and mud from water treatment. Among the screened microorganisms, eight halotolerant bacteria grew at NaCl concentrations up to 4 M. These cultures were classified based on phylogenetic characteristics and comparative partial 16S rRNA gene sequence analysis as belonging to the genera Staphylococcus, Bacillus and Brevibacterium. The results of this study describe the ability of these halotolerant bacteria to produce some classes of hydrolases, namely, lipases, proteases, amylases and cellulases, and biopolymers. The strain characterized as of Brevibacterium avium presented cellulase and amylase activities up to 4 M NaCl and also produced EPSs and PHAs. These results indicate the biotechnological potential of certain microorganisms recovered from the composting process, including halotolerant species, which have the ability to produce enzymes and biopolymers, offering new perspectives for environmental and industrial applications.

Determinação da capacidade antioxidante de produtos naturais in vitro pelo método do DPPH•: estudo de revisão / Determination in vitro of the antioxidant capacity of natural products by the DPPH• method: review study

RESUMO: Os antioxidantes podem ser de grande benefício para a melhoria da qualidade de vida, já que eles têm a capacidade de proteger um organismo dos danos causados pelos radicais livres, prevenindo ou adiando o início de várias doenças. Uma das técnicas atualmente utilizada para detectar a presença de compostos antioxidantes, é um método baseado na eliminação do radical livre estável 1,1-difenil-2-picrilhidrazil (DPPH•). Este método é considerado fácil, preciso, rápido, simples, e econômico, sendo adequado para a determinação da capacidade antioxidante de substâncias puras e misturas. O objetivo deste artigo de revisão é fornecer informações sobre esse método. A pesquisa foi realizada usando o termo radical DPPH•, capacidade antioxidante-DPPH• e método DPPH• em periódicos, tais como: Pubmed, Wiley Online Library, ACS Publications, SpringerLink e ScinceDirect até janeiro de 2014

ABSTRACT: Determination in vitro of the antioxidant capacity of natural products by the DPPH•method: review study. Antioxidants can be of great benefit to improve the quality of life, since they have the ability to protect an organism from damage caused by free radicals, preventing or delaying the onset of various diseases. One of the techniques currently used to detect the presence of antioxidant compounds is a method based on the elimination of the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH•). This method is considered easy, accurate, rapid, simple and inexpensive, and it is suitable for the determination of the antioxidant capacity of pure substances and blends. The aim of this review article is to provide information on this method. This research was performed using the terms DPPH• radical, antioxidant capacity - DPPH• and DPPH• method in journals such as Pubmed, Wiley Online Library, ACS Publications, SpringerLink and ScinceDirect up to January 2014

Preparation and characterization of microcapsules of Pterodon pubescens Benth. by using natural polymers

An oleaginous fraction obtained from an alcohol extract of the fruit of Pterodon pubescens Benth. (FHPp) was microencapsulated in polymeric systems. These systems were developed using a complex coacervation method and consisted of alginate/medium-molecular-weight chitosan (F1-MC), alginate/chitosan with greater than 75% deacetylation (F2-MC), and alginate/low-molecular-weight chitosan (F3-MC). These developed systems have the potential to both mask the taste of the extract, and to protect its constituents against possible chemical degradation. The influence of the formulation parameters and process were determined by chemical profiling and measurement of the microencapsulation efficiency of the oleaginous fraction, and by assessment of microcapsule morphology. The obtained formulations were slightly yellow, odorless, and had a pleasant taste. The average diameters of the microcapsules were 0.4679 µm (F2-MC), 0.5885 µm (F3-MC), and 0.9033 µm (F1-MC). The best formulation was F3-MC, with FHPp microencapsulation efficiency of 61.01 ± 2.00% and an in vitro release profile of 75.88 ± 0.45%; the content of vouacapans 3-4 was 99.49 ± 2.80%. The best model to describe the release kinetics for F1-MC and F3-MC was that proposed by Higuchi; however, F2-MC release displayed first-order kinetics; the release mechanism was of the supercase II type for all formulations.

Uma fração oleaginosa obtida do extrato etanólico de frutos de Pterodon pubescens Benth (FHPp) foi microencapsulada em um sistema polimérico. Estes sistemas foram desenvolvidos utilizando o método de coacervação complexa, constituído de alginato/quitosana massa molecular média (F1-MC), alginato/quitosana com desacetilação superior a 75% (F2-MC) e alginato/quitosana de massa molecular baixa (F3-MC). Estes sistemas desenvolvidos têm o potencial tanto de mascarar o sabor do extrato, quanto de protegê-lo de possível degradação química. A influência dos parâmetros de formulação e processo foram determinadas por caracterização química, determinação da eficiência de microencapsulação da fração oleaginosa e por avaliação morfológica da microcápsula. As formulações mostraram-se ligeiramente amareladas, inodoras e com sabor agradável. Os diâmetros médios das microcápsulas foram de 0,4679 µm (F2-MC), 0,5885 µm (F3-MC) e 0,9033 µm (F1-MC). A melhor formulação foi F3-MC, considerando-se que apresentou eficiência de encapsulação de 61,01 ± 2,00%, e perfil de liberação in vitro de 75,88 ± 0,45%; o conteúdo dos vouacapanos 3-4 foi 99,49 ± 2,80%. O melhor modelo para descrever a cinética de liberação foi o modelo proposto por Higuchi para F1-MC e F3-MC, entretanto, para F2-MC foi o modelo de primeira ordem, e o mecanismo de liberação foi do tipo super caso II para todas as formulações.

Avaliação da atividade antineoplásica do extrato etanólico da própolis g6 baiana / Evaluation of the antineoplastic activity of the ethanol extract of propolis g6 Bahia

O câncer é uma doença caracterizada pelo processo proliferativo descontrolado de células transformadas. Devido à possibilidade de metástase, o melanoma cutâneo é considerado um dos cânceres mais agressivos. Produtos naturais derivados de plantas e outros organismos têm sido utilizados como fonte para o desenvolvimento de quimioterápicos empregados no tratamento de diversos tipos de câncer, inclusive do melanoma. A própolis é um produto natural produzido por abelhas a partir de exudatos de brotos e botões florais, e apresenta uma composição química complexa que influência sua atividade biológica. O presente trabalho propõe a investigação da atividade antineoplásica do extrato etanólico da própolis G6 baiana (EEPG6)...

Cancer is a disease process characterized by uncontrolled proliferation of transformed cells. Due to the possibility of metastasis, cutaneous melanoma is considered one of the most aggressive cancers. Natural products derived from plants and other organisms have been used as a source for the development of chemotherapeutic agents used in the treatment of various cancers, including melanoma. Propolis is a natural product produced by bees from exudates shoots and buds, and has a complex chemical composition that influence their biological activity. This study aims to investigate the anticancer activity of ethanol extract of G6 propolis from Bahia (EEPG6)...

The phytochemistry and biological aspects of Caryocaraceae family / Aspectos fitoquímicos e biológicos da família Caryocaraceae

The Caryocaraceae family is constituted of 25 species distributed in two genera (Caryocar and Anthodiscus). Plants of this family have been used in several phytochemical studies for isolation and characterization of chemical compounds. Some of these studies evaluated in vitro and in vivo biological activities of extracts and pure substances isolated from plants of this family. Nine species of Anthodiscus genus have been described, while no phytochemical study related to them has been reported. On the other hand, Caryocar genus presents 16 species with several medicinal uses like for the treatment of colds and bronchitis, in the prevention of tumours, as a regulating agent of the menstrual flow, to treat ophthalmological problems and for the cure of hematomas and bruises. Some species of this genus were targeted by phytochemical studies and presented, in their composition, the following classes of secondary metabolites: triterpenes, fatty acids, tannins, carotenoids, triterpenic saponins, phenolic coumarins, phenolic glycosides, and others. The fruits of Caryocar species are very nutritive, containing in their composition fibers, proteins, carbohydrates and minerals. Seeds have been widely used as oil source with nutritional and cosmetic value. The biological evaluation of some species was carried out by using relevant biological assays such as: antioxidant, allelopathic and antifungal activities against Biomphalaria glabrata and toxicity on Artemia salina.

A família Caryocaraceae é constituída por 25 espécies distribuídas em dois gêneros (Caryocar e Anthodiscus). Plantas desta família têm sido utilizadas em diversos estudos fitoquímicos para isolamento e caracterização de constituintes químicos. Alguns destes estudos avaliaram atividades biológicas in vitro e in vivo de extratos e substâncias puras isoladas a partir de plantas desta família. São descritas nove espécies dentro do gênero Anthodiscus e nenhum estudo fitoquímico relacionado a elas foi relatado. Por outro lado, o gênero Caryocar apresenta 16 espécies com diversos usos medicinais, tais como: para o tratamento de resfriados, bronquites, na prevenção de tumores, como reguladores do fluxo menstrual, em problemas oftalmológicos, e na cura de hematomas e contusões. Algumas espécies deste gênero foram submetidas a estudos fitoquímicos e apresentaram, em sua composição, as seguintes classes de metabólitos secundários: triterpenos, ácidos graxos, taninos, carotenoides, saponinas triterpênicas, cumarinas, glicosídeos fenólicos, entre outros. Os frutos de espécies Caryocar são muito nutritivos contendo em sua composição, fibras, proteínas, carboidratos e minerais. As sementes têm sido amplamente usadas como fonte de óleo com valor nutricional e cosmético. A avaliação biológica de algumas espécies foi realizada utilizando-se testes biológicos relevantes, entre eles: a atividade antioxidante, alelopática, antifúngica, contra Biomphalaria glabrata, e toxicidade sobre Artemia salina.

Stability evaluation of organic Lip Balm

Rising global demand for natural products whose production is harmless to the environment has stimulated the development of natural cosmetics and, within this category, organics (95% organic raw materials). The image of environmentally friendly production is one of the strongest attractions of organic products. Lip balm is a cosmetic product similar to lipstick whose purpose is to prevent lip dryness and protect against adverse environmental factors. The product's characteristics are: resistance to temperature variations, pleasant flavor, innocuousness, smoothness during application, adherence and easy intentional removal. This work involved the development of a lip balm formulated with certified organic raw materials and the execution of stability tests: fusion point determination, evaluation of organoleptic characteristics (color, odor and appearance) and functionality evaluation (spreadability test). The formulation selected after the Preliminary Stability Test was submitted to the Normal Stability Test under the following storage conditions (temperature): Room Temperature (22.0 ± 3.0 ºC), Oven (40.0 ± 2.0 ºC) and Refrigerator (5.0 ± 1.0 ºC), for 90 days. Under the Refrigerator and Room Temperature conditions, spreadability proved adequate, but the surface presented white spots, characterizing the fat bloom, a phenomenon involving the recrystallization of cocoa butter. Storage at 40.0 ± 2.0 ºC (Oven) caused loss of functionality according to the spreadability test, in addition to changes in color, although the aspect was uniform since the fat bloom was not observed (white spots on the surface). The odor remained stable under all conditions as did the melting point, which had a mean of 72.9 ± 1.7 ºC throughout the course of stability testing (90 days).

O aumento da demanda global por produtos naturais, cuja produção não envolva nenhum dano ao meio ambiente, tem estimulado o desenvolvimento de cosméticos naturais e, dentro desta categoria, dos produtos orgânicos (que contêm 95% de matérias-primas orgânicas). O protetor labial é um produto cosmético semelhante ao batom que tem a finalidade de prevenir o ressecamento dos lábios, mantendo a hidratação, e protegê-los contra fatores ambientais adversos. Este trabalho envolveu o desenvolvimento de um protetor labial formulado com matérias-primas orgânicas e avaliação dos parâmetros de estabilidade, como ponto de fusão, características organolépticas e funcionalidade (teste de espalhabilidade). A formulação selecionada após o Estudo de Estabilidade Preliminar foi submetida à Avaliação Normal de Estabilidade, nas seguintes condições de armazenamento (temperatura): Ambiente (22,0 ± 3,0 ºC), Estufa (40,0 ± 2,0 ºC) e Geladeira (5,0 ± 1,0 ºC), por 90 dias. Nas condições de armazenamento em geladeira ou ambiente, a espalhabilidade foi adequada, mas a superfície apresentou pontos esbranquiçados, caracterizando o fenômeno chamado fat bloom, que está relacionado à recristalização da manteiga de cacau. O armazenamento à temperatura elevada (40,0 ± 2,0 ºC) provocou perda de funcionalidade, de acordo com o teste de espalhabilidade, e mudança de cor, apesar do aspecto permanecer uniforme, visto que não foi observado o fenômeno fat bloom. O odor manteve-se estável em todas as condições, assim como o ponto de fusão, com valor médio de 72,9 ºC ± 1,7 ºC durante todo o período de avaliação do teste de estabilidade (90 dias).

Antibacterial evaluation of Styrax pohlii and isolated compounds

The antibacterial activity of the compounds egonol (1) and homoegonol (2), of the crude ethanolic extract of Styrax pohlii (Styracaceae) aerial parts (EE), and of its n-hexane (HF), EtOAc (EF), n-BuOH (BF), and hydromethanolic (HMF) fractions was evaluated against the following microorganisms: Streptococcus pneumoniae (ATCC 6305), S. pyogenes (ATCC 19615), Haemophilus influenzae (ATCC 10211), Pseudomonas aeruginosa (ATCC 27853), and Klebsiella pneumoniae (ATCC 10031). The broth microdilution method was used for determination of the minimum inhibitory concentration (MIC) during preliminary evaluation of antibacterial activity. The EE yielded MIC values of 400 µg/mL for S. pneumoniae and P. aeruginosa and 300 µg/mL for H. influenzae. The HF and EF fractions exhibited enhanced antibacterial activity, with MIC values of 200 µg/mL against S. pneumoniae, but only EF displayed activity against H. influenzae (MIC 200 µg/mL). The best MIC value with compounds 1 and 2 (400 µg/mL) was obtained for (1) against S. pneumoniae and P. aeruginosa. Therefore, 1 exhibited weak antibacterial activity against these standard strains.

As atividades antimicrobianas das substâncias egonol (1) e homoegonol (2), do extrato etanólico das partes aéreas de Styrax pohlii (Styracaceae) (EE), bem como das frações n-hexano (HF), AcOEt (EF), n-BuOH (BF) e hidrometanólica (HMF) foram avaliadas frente aos seguintes microorganismos: Streptococcus pneumoniae (ATCC 6305), S. pyogenes (ATCC 19615), Haemophilus influenzae (ATCC 10211), Pseudomonas aeruginosa (ATCC 27853) e Klebsiella pneumoniae (ATCC 10031). O método de microdiluição em caldo foi utilizado para a determinação da concentração inibitória mínima (CIM) na avaliação preliminar da atividade antimicrobiana. EE mostrou valores de CIM de 400 µg/mL para S. pneumoniae e P. aeruginosa, e 300 µg/mL para H. influenzae. As frações HF e EF apresentaram melhora na atividade antimicrobiana, com valores de CIM de 200 µg/mL frente S. pneumoniae, mas apenas EF apresentou ação contra H. influenzae (200 µg/mL). Em relação às substâncias 1 e 2, o melhor valor de CIM (400 µg/mL) foi obtido por 1 frente a S. pneumoniae e P. aeruginosa, que exibiu fraca atividade antimicrobiana contra estas cepas padrões.

Medicinal plants with teratogenic potential: current considerations

The aim of this study was to present the implications of the use of herbs during pregnancy, pointing out those that should be avoided during this condition because of their abortifacient and/or teratogenic potential. We carried out searches in the databases ScienceDirect, Scielo and Google Scholar, adopting as criteria for inclusion: book chapters and/or complete articles (with abstract), available in English, Portuguese or Spanish, published from 1996 to in 2011. After a pre-selection of 83 articles, 49 bibliographies were used in the manufacturing end of the article, where 25 were from the Scielo database, 18 from ScienceDirect and 6 from Google Scholar. From the articles studied, we identified the four most commonly used plants as emmenagogue/abortifacient agents by patients of the Department of Prenatal SUS: senne, arruda, boldo and buchinha-do-norte or cabacinha. Thus, we conclude that people often adhere to the maxim "if it's natural, it does no harm" in their rational use of natural products, without the right guidance, believing that these products are safe to use. This usage is even more worrisome among the elderly, pregnant women and children. Regarding the safety of these products, some information and reliable data are scarce or contradictory.

Este trabalho busca as implicações atuais sobre o uso de plantas medicinais durante a gravidez, alertando sobre aquelas que devem ser evitadas nesse período por serem potencialmente abortivas e/ou teratogênicas. Para tanto, foram realizadas buscas nas bases de dados Sciencedirect, Scielo e Google scholar, adotando-se como critérios de inclusão capítulos de livros e/ou artigos completos (com abstract) e disponíveis, em português, inglês ou espanhol, publicados de 1996 a 2011. Após uma pré-seleção de 83 artigos, 49 bibliografias foram utilizadas na confecção final do artigo, sendo 25 provenientes da base de dados Scielo, 18 do Sciencedirect e 06 do Google scholar. A partir dos artigos estudados, identificaram-se as quatro plantas mais utilizadas como emenagogas/abortivas por pacientes do Serviço de Pré-Natal do SUS: senne, arruda, boldo e buchinha-do-norte ou cabacinha. Assim, é possível concluir que, muitas vezes, a população se utiliza da máxima "se é natural, não faz mal" para fazer uso irracional de produtos naturais, sem a correta orientação, acreditando que esses produtos sejam incapazes de provocar qualquer dano. Esse uso é ainda mais preocupante quando realizado por idosos, gestantes e crianças. Em relação à segurança do uso desses produtos, algumas informações e dados confiáveis ainda são escassos ou contraditórios.