Toxicity and Anti-Inflammatory Effects of Agave sisalana Extract Derived from Agroindustrial Residue.

BACKGROUND: In several countries, the leaf juice of Agave sisalana (also known as sisal) is widely used topically, especially as an antiseptic, and orally for the treatment of different pathologies. However, in Brazil, which is the largest producer of Agave sisalana, its residue, which represents the majority of its weight, has been thrown away. For this reason, the determination of the pharmacological and toxicological potentials of sisal residue and its possible therapeutic use is seen as a way to contribute to the sustainable development and social promotion of the largest producer of sisal in Brazil, the interior of Bahia State, which is among the poorest areas in the country. Given the scarcity of available scientific studies on the pharmacological and toxicological properties of sisal residue juice, this study aimed to promote the acid hydrolysis of this juice to potentiate the anti-inflammatory effect already described in the literature. Furthermore, it aimed to evaluate the toxicological profile of the hydrolyzed extract (EAH) and to determine its acute toxicity, as well as its side effects on the reproductive aspects of rats. METHOD: The anti-inflammatory effect of EAH was evaluated in vitro using the induction of hemolysis by hypotonic solution and in vivo in rats using the carrageenan-induced paw edema test and the xylene-induced ear edema test. The acute toxicity, resulting from a single-dose administration, was investigated for some manifestation of toxic symptoms related to motor control and consciousness in rats. At a concentration of 100 mg/kg, by repeated doses, the reproductive toxicity effects of EAH in rats were assessed. RESULTS: In vitro anti-inflammatory activity was positive using the human red blood cell membrane stabilization method. In both in vivo tests used to assess the anti-inflammatory activity, EAH (at three doses) significantly inhibited edema when compared to the control group. At a dose of 50 mg/kg, EAH exhibited a greater effect than indomethacin, a nonsteroidal anti-inflammatory drug with known activity. In vivo toxicological studies have shown that EAH does not present toxic effects when administered orally in a single dose, up to 1000 mg/kg. Finally, EAH promoted a gonadotoxic effect and increased the embryonic mortality rate after implantation. CONCLUSIONS: It is suggested that the anti-edematogenic effect of the acid hydrolysis extract from sisal juice is due to the high concentration of steroidal sapogenins. Therefore, this extract can be considered a potential new anti-inflammatory or even an important sapogenin source for the development of steroidal glucocorticoids. However, further studies are needed to elucidate the chemical composition of sisal juice. Regarding toxicology studies, EAH did not show cytotoxic and clastogenic potentials, but it presented a powerful reproductive toxic effect in rats.

Anti-Inflammatory Effect and Toxicological Profile of Pulp Residue from the Caryocar Brasiliense, a Sustainable Raw Material.

Caryocar brasiliense Cambess is a plant species typical of the Cerrado, a Brazilian biome. The fruit of this species is popularly known as pequi, and its oil is used in traditional medicine. However, an important factor hindering the use of pequi oil is its low yield when extracted from the pulp of this fruit. Therefore, in this study, with aim of developing a new herbal medicine, we an-alyzed the toxicity and anti-inflammatory activity of an extract of pequi pulp residue (EPPR), fol-lowing the mechanical extraction of the oil from its pulp. For this purpose, EPPR was prepared and encapsulated in chitosan. The nanoparticles were analyzed, and the cytotoxicity of the encapsu-lated EPPR was evaluated in vitro. After confirming the cytotoxicity of the encapsulated EPPR, the following evaluations were performed with non-encapsulated EPPR: in vitro anti-inflammatory activity, quantification of cytokines, and acute toxicity in vivo. Once the anti-inflammatory activity and absence of toxicity of EPPR were verified, a gel formulation of EPPR was developed for topical use and analyzed for its in vivo anti-inflammatory potential, ocular toxicity, and previous stability assessment. EPPR and the gel containing EPPR showed effective anti-inflammatory activity and lack of toxicity. The formulation was stable. Thus, a new herbal medicine with anti-inflammatory activity can be developed from discarded pequi residue.

Medicinal plants of the brazilian cerrado: knowing to preserve / Plantas medicinais do cerrado brasileiro: sabendo preservar

The Cerrado is the second largest biome in Brazil and presents an immeasurable and still underexplored ecological diversity. Despite the exuberance of its endemic species, it is one of the 25 global hotspots, due to a high natural biodiversity wealth along with an expressive environment destruction. In this study, we surveyed the knowledge on medicinal use of Cerrado plants held by individuals living in a predominantly Cerrado region. A semi-structured individual questionnaire for qualitative socio-economic characterization and medicinal use of plants was applied to Public Health Service users of the city of Assis, State of Sao Paulo, Brazil. This study was approved by the Ethics Committee of the Assis Regional Hospital (Protocol 4812010). Out of 149 respondents, 90.6% reported knowledge and/or use of plants for therapeutic purposes. Among 115 mentioned plant species, only 11.4% belong to the Cerrado. We also evaluated how matching were the reported uses and the respective published data from scientific studies on the plants' medicinal properties. It was verified that for the few Cerrado plants cited, the respondents described several medicinal applications not scientifically described. More precisely, 60.5% of all medicinal applications were not found in the scientific literature. Besides that, many of the therapeutic effects described in the literature for the Cerrado species were not cited by the interviewed population. Our results indicate a relative unawareness of people on the medicinal potential of the native species of their residence region. We suggest that strengthening connection between popular and scientific knowledge, along with spreading such knowledge, could contribute for an improved valuation about the Cerrado biome and consecutive preservation of it.KEYWORDS: Popular knowledge. Scientific knowledge. Valuation about the biome. INTRODUCTION Use of medicinal plants dates back to ancient times (DUTRA et al., 2016) and, over time, accumulated empirical evidence produced from popular knowledge has enabled incorporation of phytotherapy into traditional medicine with positive results (SANTOS et al., 2011). With the advent of ethnobotany and ethnopharmacology, many of these plants began to be safely used in the production ofherbal medicines for treatment of different diseases, such as infections, tissue inflammation, and pain (EKOR, 2014). It is currently known that several secondary metabolites produced by plants not only protect themselves from herbivory and pathogens, for instance (FÜRSTENBERG-HÄGG; ZAGROBELNY; BAK, 2013; SANCHÉZ-SANCHÉZ; MORQUECHO-CONTRERAS, 2017), but also have beneficial effects on human health (TAIZ; ZEIGER, 2010). However, in many countries, including those that hold a large biodiversity, the native medicinal flora is still barely studied by scientific methods (RIBEIRO et al., 2014). The Cerrado is the second largest biome after the Amazon in Brazil. Although the extensive area of 2,036,448 km2 occupied nowadays by this biome (BARBOSA, 2017), much of the Cerrado has already been transformed into pasture, grain crops or devastated for other uses (KLINK; MACHADO, 2005). Currently, only 8,21% of its total area is fully protected (BARBOSA, 2017). As a result, it is one of the most threatened biomes in the world. According to Mittermeier et al. (2005), the Brazilian Cerrado is one of the 25 global hotspots, areas with concentration of endemic species and exceptional ongoing destruction. Many communities resident in Cerrado regions are comprised of poor people with restricted access to public health services and often dependent Received: 14/05/18 Accepted: 20/11/19

O Cerrado é o segundo maior bioma do Brasil, apresenta uma diversidade ecológica imensurável e ainda pouco explorada. Apesar da exuberância de suas espécies endêmicas, é um dos 25 hotspots globais, pois apresenta alta riqueza natural em termos de biodiversidade e destruição expressiva de seu meio ambiente. Neste estudo, pesquisamos o conhecimento sobre o uso medicinal de plantas do Cerrado entre indivíduos que vivem em uma região predominantemente do Cerrado. Um questionário individual semiestruturado com perguntas de caráter socioeconômicas qualitativas e referentes ao uso medicinal de plantas foi aplicado aos usuários do Serviço de Saúde Pública da cidade de Assis, Estado de São Paulo, Brasil. Este estudo foi aprovado pelo Comitê de Ética do Hospital Regional de Assis (Protocolo 4812010). Dos 149 entrevistados, 90,6% relataram conhecimento e / ou uso de plantas para fins terapêuticos. Entre as 115 espécies de plantas mencionadas, 11,4% pertencem ao Cerrado. Também avaliamos a correlação entre os usos relatados e os respectivos dados publicados em estudos científicos sobre as propriedades medicinais das plantas.Verificou-se que, para as poucas plantas de Cerrado citadas, os entrevistados descreveram diversas aplicações medicinais não descritas cientificamente. Mais precisamente, 60,5% do total das aplicações medicinais não foram encontrados na literatura científica. Além disso, muitos dos efeitos terapêuticos descritos na literatura para as espécies do Cerrado não foram citados pela população entrevistada. Portanto, sugerimos que o fortalecimento da conexão entre conhecimento popular e científico, aliado à disseminação desse conhecimento, poderia contribuir para uma maior valorização do bioma Cerrado e consequentemente a preservação do mesmo.

Analysis of antioxidant, cytotoxic and mutagenic potential of Agave sisalana Perrine extracts using Vero cells, human lymphocytes and mice polychromatic erythrocytes

Brazilian Northeast is the world's largest producer of Agave sisalana Perrine for the supply of the sisal fiber. About 95% of plant biomass, which comprise the mucilage and sisal juice, is considered a waste residual is discarded in the soil. However, the sisal juice is rich in steroidal saponins, which exhibits different pharmacological properties. Despite this, natural products are not necessarily safe. Based on this, this study analyzed the antioxidant, cytotoxic and mutagenic potential of three extracts derived from acid hydrolysis (AHAS), dried precipitate (DPAS) and hexanic of A. sisalana (HAS). These analyses were performed by in vitro and in vivo methods, using Vero cells, human lymphocytes and mice. Results showed that AHAS 50 and 100 can be considered a useful antineoplastic candidate due to their antioxidant and cytotoxic activity, with no genotoxic/clastogenic potential in Vero cells and mice. Although the comet assay in human lymphocytes has showed that the AHAS 25, AHAS 50 and AHAS 100 can lead to DNA breaks, these extracts did not promote DNA damages in mice bone marrow. Considering the different mutagenic responses obtained with the different methods employed, this study suggest that the metabolizing pathways can produce by-products harmful to health. For this reason, it is mandatory to analyze the mutagenic potential by both in vitro and in vivo techniques, using cells derived from different species and origins.

Analysis of antioxidant, cytotoxic and mutagenic potential of Agave sisalana Perrine extracts using Vero cells, human lymphocytes and mice polychromatic erythrocytes

Brazilian Northeast is the world's largest producer of Agave sisalana Perrine for the supply of the sisal fiber. About 95% of plant biomass, which comprise the mucilage and sisal juice, is considered a waste residual is discarded in the soil. However, the sisal juice is rich in steroidal saponins, which exhibits different pharmacological properties. Despite this, natural products are not necessarily safe. Based on this, this study analyzed the antioxidant, cytotoxic and mutagenic potential of three extracts derived from acid hydrolysis (AHAS), dried precipitate (DPAS) and hexanic of A. sisalana (HAS). These analyses were performed by in vitro and in vivo methods, using Vero cells, human lymphocytes and mice. Results showed that AHAS 50 and 100 can be considered a useful antineoplastic candidate due to their antioxidant and cytotoxic activity, with no genotoxic/clastogenic potential in Vero cells and mice. Although the comet assay in human lymphocytes has showed that the AHAS 25, AHAS 50 and AHAS 100 can lead to DNA breaks, these extracts did not promote DNA damages in mice bone marrow. Considering the different mutagenic responses obtained with the different methods employed, this study suggest that the metabolizing pathways can produce by-products harmful to health. For this reason, it is mandatory to analyze the mutagenic potential by both in vitro and in vivo techniques, using cells derived from different species and origins.

Interações medicamentosas potenciais com benzodiazepínicos em prescrições médicas de pacientes hospitalizados / Potential drug interactions with benzodiazepines in medical prescriptions of hospitalized patients

A prática de associações medicamentosas é comum em pacientes hospitalizados, Esta prática é muitas vezes necessária, principalmente em pacientes psiquiátricos, uma vez que, juntamente com as doenças neuropsiquiátricas, podem ocorrer outras comorbidades, Entretanto, esta prática pode favorecer a ocorrência de interações medicamentosas com consequente potencialização de diferentes efeitos adversos, Diante deste quadro, o presente trabalho teve como objetivo avaliar a ocorrência de potenciais interações medicamentosas com os benzodiazepínicos, prescritos aos pacientes internados na Clínica Psiquiátrica do Hospital Regional de Assis ? SP, a fim de gerar informações que contribuam para a eficácia do tratamento estabelecido ao paciente, Para isso, foi realizada uma análise de 100 prescrições médicas, nas quais foram avaliadas as possibilidades de ocorrência de interações medicamentosas entre os diferentes fármacos da classe dos benzodiazepínicos administrados concomitantemente, bem como com outras classes de fármacos, Por meio deste estudo, verificou-se que das 100 prescrições médicas analisadas 93 apresentaram a possibilidade de ocorrência de interações farmacológicas entre benzodiazepínicos e com outras classes de fármacos, totalizando 356 possíveis interações, Desse total, destacam-se as associações dos benzodiazepínicos com os antipsicóticos, anti-histamínicos, antiepilépticos e antidepressivos, as quais podem potencializar a manifestação de inúmeros efeitos adversos, em destaque, a exacerbação do efeito depressor do sistema nervoso central, com repercussões que podem variar desde a manifestação clínica leve até risco de êxito letal, Neste contexto, busca-se com este trabalho contribuir para uma melhor compreensão, reconhecimento e intervenção precoce ou profilática em situações clínicas decorrentes de interações farmacológicas entre diferentes classes de fármacos com os benzodiazepínicos...

The practice of drug combinations is common in hospitalized patients. This practice is often necessary, especially in psychiatric patients, since other comorbidities may occur in parallel with neuropsychiatric disorders. However, this practice may favor the occurrence of drug interactions with consequent increase of different adverse effects. Facing this situation, the present study aimed to evaluate the occurrence of potential drug interactions with benzodiazepines prescribed to hospitalized patients at the Psychiatric Clinic of the Hospital Regional de Assis - SP, in order to generate information that contributes to the effectiveness of the treatment provided to patient. To this end, an analysis of 100 medical prescriptions was performed, in which were evaluated the possibility of drug interactions between the different medications from the class of benzodiazepines concomitantly administered, as well as other classes of drugs. By means of this study, it was verified that the 100 analyzed prescriptions 93 presented the possibility of different pharmacological interactions between benzodiazepine, and with other classes of drugs, totaling 356 possible interactions. Of this total stand out the associations of benzodiazepines with antipsychotics, antihistamines, antiepileptics and antidepressants, which can enhance the expression of numerous adverse effects, highlighted the exacerbation of depressant effect on the central nervous system, with effects that can range from mild clinical manifestation until risk of lethal outcome. In this context, it seeks in this work to contribute to a better understanding, recognition and early or prophylactic intervention in clinical situations arising from interactions between different pharmacological classes of drugs with benzodiazepines...

Participação da via serontonérgica que conecta o núcleo mediano da rafe ao hipocampo dorsal na mediação das respostas comportamentais defensivas de ratos submetidos ao labirinto em T elevado / Involvement of the serotonergic pathway connecting the median raphe nucleus to the dorsal hippocampus in the modulation of defensive behaviors in rats submitted to the elevated T-maze

oEvidências na literatura indicam o envolvimento de neurônios serotonérgicos do núcleo mediano da rafe (NMR) na ansiedade. Evidências sugerem ainda que estes neurônios serotonérgicos desempenham funções regulatórias diferentes sobre os comportamentos defensivos que têm sido associados a subtipos específicos de distúrbios de ansiedade. Assim, tem sido mostrado que no labirinto em T elevado (LTE) a lesão eletrolítica do NMR prejudica tanto a resposta de esquiva inibitória como a fuga, enquanto a destruição seletiva dos neurônios serotonérgicos do NMR pela neurotoxina 5,7 DHT prejudica somente a esquiva inibitória. Neste teste, enquanto a resposta de esquiva inibitória tem sido relacionada ao distúrbio de ansiedade generalizada, a resposta de fuga tem sido associada ao distúrbio de pânico. Assim, esses resultados sugerem que os neurônios serotonérgicos do NMR exercem um controle preferencial sobre o comportamento defensivo que tem sido associado ao distúrbio de ansiedade generalizada. O objetivo do presente estudo foi o de estudar o envolvimento de neurônios serotonérgicos do NMR e da via que conecta estes neuronios ao hipocampo dorsal na mediação de comportamentos defensivos gerados no LTE. Para isso, nós avaliamos inicialmente o efeito da administração intra-NMR de drogas que afetam de maneira seletiva e não seletiva a atividade dos neurônios serotonérgicos. Os resultados mostram que a microinjeção de muscimol, um composto que inibe a atividade dos neurônios do NMR, prejudicou a esquiva inibitória e facilitou a resposta de fuga, enquanto a injeção intra-NMR de FG 7142 ou ácido caínico, drogas que estimulam esses neurônios, facilitaram a esquiva inibitória, mas prejudicaram a resposta de fuga...(AU)