Toxicological Profile and Anti-Inflammatory Effect of Mucoadhesive Gel from Residues of Agave sisalana and Punica granatum.

Inflammation is a natural protective reaction of the body against endogenous and exogenous damage, such as tissue injuries, trauma, and infections. Thus, when the response is adequate, inflammation becomes a defense mechanism to repair damaged tissue, whereas when the response is inadequate and persistent, the increase in inflammatory cells, cytosines, and chymosins impair tissue regeneration and promote a response harmful to the organism. One example is chronic tissue inflammation, in which a simple lesion can progress to ulcers and even necrosis. In this situation, the anti-inflammatory medications available in therapy are not always effective. For this reason, the search for new treatments, developed from medicinal plants, has increased. In this direction, the plants Agave sisalana (sisal) and Punica granatum (pomegranate) are rich in saponins, which are secondary metabolites known for their therapeutic properties, including anti-inflammatory effects. Although Brazil is the world's leading sisal producer, approximately 95% of the leaves are discarded after fiber extraction. Similarly, pomegranate peel waste is abundant in Brazil. To address the need for safe and effective anti-inflammatory treatments, this study aimed to create a topical mucoadhesive gel containing a combination of sisal (RS) and pomegranate residue (PR) extracts. In vitro experiments examined isolated and combined extracts, as well as the resulting formulation, focusing on (1) a phytochemical analysis (total saponin content); (2) cytotoxicity (MTT assay); and (3) a pharmacological assessment of anti-inflammatory activity (phagocytosis, macrophage spreading, and membrane stability). The results revealed saponin concentrations in grams per 100 g of dry extract as follows: SR-29.91 ± 0.33, PR-15.83 ± 0.93, association (A)-22.99 ± 0.01, base gel (G1)-0.00 ± 0.00, and association gel (G2)-0.52 ± 0.05. In MTT tests for isolated extracts, cytotoxicity values (µg/mL) were 3757.00 for SR and 2064.91 for PR. Conversely, A and G2 exhibited no cytotoxicity, with increased cell viability over time. All three anti-inflammatory tests confirmed the presence of this activity in SR, PR, and A. Notably, G2 demonstrated an anti-inflammatory effect comparable to dexamethasone. In conclusion, the gel containing SR and PR (i.e., A) holds promise as a novel herbal anti-inflammatory treatment. Its development could yield economic, social, and environmental benefits by utilizing discarded materials in Brazil.

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.

Antiglycation, antioxidant and cytotoxicity activities of crude extract of Turnera ulmifolia L. before and after microencapsulation process.

Turnera ulmifolia L. is used in folk medicine and it is known to have anti-hyperglycemic effect on the organism in order to reduce complications in diabetic patients. Glycation process is directly related to oxidative stress, acting as an important endogenous source, inducing the production of free radicals, and thus increasing the production of reactive oxygen species. The encapsulation technology on natural compounds can minimize and even mitigate the risk of loss of biological activity in order to maintain their activities against oxidative stress and glycation. The present study aimed to evaluate the antiglycation and antioxidant activities of T. ulmifolia extract before and after encapsulation and cytotoxicity of the crude extract. This study presents important information about the biological activities, highlighting antioxidant and antiglycation potential and no cytotoxicity of Turnera ulmifolia crude extract, a species of genus Turnera that has been poorly studied. T. ulmifolia crude extract presented flavonoids as main active compounds. The results showed a promising activity in scavenging free and peroxyl radicals, chelating iron ions and inhibiting BSA glycation. In addition, this study showed the possible encapsulation of bioactive compounds using maltodextrin as wall material.

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.

Toxicological, genotoxic and antioxidant potential of pyrostegia venusta / Potencial toxicológico, genotóxico e antioxidante de Pyrostegia venusta

Pyrostegia venusta is usually found in the secondary growth of the Atlantic forests, and in the Brazilian Savanna. Flowers and leaves of this plant are used in folk remedies for treating a wide variety of healthy conditions, this way is important evaluate its safety and antioxidant potential for this applications. For this, was made a ethanolic extract from its flowers and analyzed with toxicological,genotoxicity and antioxidant tests, the toxicological analysis was made by reproductive toxicity in rats and clatogenicity/aneugenicity in human lymphocytes. The genotoxicity was studied by micronucleus test mice bone marrow. The antimutagenic test in root cells of Allium cepa, the antioxidant assays used was DPPH, FRAP, Lipid Perxidation and REM, beyond of that the extract was analyzed in HPLC showing the profile of its compounds. The toxicological analysis showed that P. venusta has no negative significant effect on reproductive and cellular level. The micronucleus test in mouse bone marrow, the extract protected cells from cyclophosphamide, mutagenic compound, in a similar way. The A. cepa test showed that the extract reduced chromosomal disorders formations. The antioxidant activity of extract was significant, except in REM test. The phytochemical analysis showed the presence of flavonoids compounds. P. venusta extract does not present reproductive toxicity and genotoxic effects. However, the extract of this species showed antigenotoxic and antioxidant potential, possibly due to the different flavonoid compounds present in its extract.

Pyrostegia venusta é geralmente encontrada no crescimento secundário das florestas atlânticas e na savana brasileira. Flores e folhas desta planta são utilizadas em remédios populares para tratar uma grande variedade de doenças, desta forma é importante avaliar a segurança e o potencial antioxidante para estas aplicações. Para tanto, o extrato etanólico das flores foi avaliado com testes toxicológicos, genotóxicos e antioxidants. A análise toxicológica foi realizada por meio da toxicidade reprodutiva em ratos e a clatogenicidade/aneugenicidade em linfócitos humanos, a genotoxicidade foi estudada por teste de micronúcleo em medula óssea de camundongo. A antimutagenicidade em células da raiz de Allium cepa. Os ensaios antioxidantes utilizados foram DPPH, FRAP, TARBS e MRE. O extrato foi analisado em HPLC. A análise toxicológica reprodutiva mostrou que P. venusta não tem efeito negativo sobre o nível reprodutivo e cellular. No teste do micronúcleo o extrato protegeu as células da ciclofosfamida, um composto mutagênico. O teste de A. cepa mostrou que o extrato reduziu as formações dos distúrbios cromossômicos. A atividade antioxidante do extrato foi significativa, exceto no teste REM. A análise fitoquímica mostrou a presença de compostos flavonoídicos. O extrato de P. venusta não apresenta toxicidade reprodutiva e efeitos genotóxicos. No entanto, o extrato desta espécie apresentou potencial antigenotóxico e antioxidante, possivelmente devido aos diferentes compostos flavonoídicos presentes em seu extrato.

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...