Bioactive Natural Products against Systemic Arterial Hypertension: A Past 20-Year Systematic and Prospective Review.

Background: Systemic arterial hypertension is one of the most common cardiovascular risks, corresponding to 45% of deaths involving CVDs. The use of natural products, such as medicinal plants, belongs to a millennial part of human therapeutics history and has been employed as an alternative anti-hypertensive treatment. Objective: The present review aims to prospect some natural products already experimentally assayed against arterial hypertension through scientific virtual libraries and patent documents over the past 20 years. Search strategy. This is a systematic review of the adoption of the PRISMA protocol and a survey of the scientific literature that synthesizes the results from published articles between 2001 and 2020 concerning the use of medicinal plants in the management of hypertension, including which parts of the plant or organism are used, as well as the mechanisms of action underlying the anti-hypertensive effect. Furthermore, a technological prospection was also carried out in patent offices from different countries in order to check technologies based on natural products claimed for the treatment or prevention of hypertension. Inclusion criteria. Scientific articles where a natural product had been experimentally assayed for anti-hypertensive activity (part of plants, plant extracts, and products derived from other organisms) were included. Data extraction and analysis. The selected abstracts of the articles and patent documents were submitted to a rigorous reading process. Those articles and patents that were not related to anti-hypertensive effects and claimed potential applications were excluded from the search. Results: Eighty specimens of biological species that showed anti-hypertensive activity were recovered, with 01 representative from the kingdom Fungi and 02 from the kingdom Protista, with emphasis on the families Asteraceae and Lamiaceae, with 6 representatives each. Leaves and aerial parts were the most used parts of the plants for the extraction of anti-hypertensive products, with maceration being the most used extraction method. Regarding phytochemical analyses, the most described classes of biomolecules in the reviewed works were alkaloids, terpenes, coumarins, flavonoids, and peptides, with the reduction of oxidative stress and the release of NO among the mechanisms of action most involved in this process. Regarding the number of patent filings, China was the country that stood out as the main one, with 813 registrations. Conclusion: The anti-hypertensive activity of natural products is still little explored in Western countries. Besides, China and India have shown more results in this area than other countries, confirming the strong influence of traditional medicine in these countries.

Chalcones Isolated from Arrabidaea brachypoda Flowers as Inhibitors of NorA and MepA Multidrug Efflux Pumps of Staphylococcus aureus.

Bacterial resistance to antibiotics has become a public health issue around the world. The present study aimed to evaluate the antibacterial activity of chalcones isolated from flowers of Arrabidaea brachypoda, and their potential as efflux pump inhibitors of Staphylococcus aureus efflux pumps. Microdilution assays were performed with natural products from A. brachypoda. Chalcones 1, 3, 4, and 5 did not show intrinsic antimicrobial activity against all S. aureus strains tested, but they were able to potentiate the Norfloxacin action against the SA1199-B (norA) strain, with a better modulating action for the 4 trimethoxylated chalcone. All chalcones were also able to potentiate the action of EtBr against SA1199-B strain, suggesting a potential NorA inhibition. Moreover, chalcone 4 was able to interfere in the activity of MepA, and interfered weakly in the QacA/B activity. Molecular docking analyzes showed that tested chalcones are capable of binding in the hydrophobic cavity of NorA and MepA, in the same Norfloxacin binding site, indicating that chalcone 4 compete with the antibiotic for the same NorA and MepA binding sites. Association of chalcone 4 with Norfloxacin could be an alternative against multidrug resistant S. aureus over-productive of NorA or MepA.

Pathophysiological investigations, anxiolytic effects and interaction of a semisynthetic riparin with benzodiazepine receptors.

We have reported Riparin A as a promising antiparasitic molecule ​​against Leishmania amazonensis promastigotes. This work evaluated the acute oral toxicity of Riparin A and its anxiolytic effects using in vivo models and computational tools. Mice were submitted to acute oral toxicity tests (Guideline OECD 423). Later, anxiety assays with Riparin A (50, 100 and 200 mg/kg: elevated plus maze, light/dark box and marble burying) were performed. Theoretical calculations analyzed interaction of Riparin A with gamma-amino butyric acid (GABA) receptors. Only Riparin A at 2000 mg/kg alter body weight, food and water consumption and urine production after 7 and/or 14 days treatment and increased serum triglycerides. There was increase in the time spent in the open arms (TSOA) and number of transitions between compartments (NTC) and decrease in number of hidden balls (NHB) in Riparin A-treated animals at 200 mg/kg (P < 0.05), whose approximate ED50 was 283.1 (156.5-397.1) mg/kg. The functional amide of Riparin A interacted with the GABAA receptor mainly at subunits α2 and ß1 and presented strong interaction with the Asp68 residue, which is part of the pharmacophore group. Riparin A was toxically safe and pharmacologically active for anxiolytic purposes, revealed NOAEL of 200 mg/kg and probably interacts with Asp68 residues of benzodiazepine receptors by hydrogen bonds.

Profile of diabetic patients accompanied by the pharmaceutical assistance of Piauí, Brazil / Perfil dos pacientes diabéticos acompanhados pela assistência farmacêutica do Piauí, Brasil

Diabetes mellitus consists of a chronic disease that currently stands out for its associated morbidity and mortality. The therapy is based on the association of different drugs and requires a change in the habits of the patients. The objective of the present study was to analyze the clinical and epidemiological profile of patients with type 2 diabetes mellitus assisted by the Specialized Component of Pharmaceutical Assistance of the state of Piauí. This was a descriptive, crosssectional study and analysis of social, demographic, economic, biochemical and anthropometric parameters. From the 93 participants, 66.7% were female, 57% had an average age of 60.5 years and 50.5% had a weight above 69 kg. The predominant family income was one minimum wage salary and the level of education reported was completed secondary education. It was found that 53.8% of the participants practiced regular physical activity and 87.1% had food restrictions. The most commonly used drug was vildagliptin. It was proven that 52.7% had unsatisfactory glycemic control considering the levels of HbA1c, as well as a necessity of a public state clinical protocol that regulates the dispensation of oral hypoglycemic agents in the state.

O diabetes mellitus consiste em uma doença crônica que atualmente se destaca por sua morbimortalidade associada. A terapia baseia-se na associação de diferentes fármacos e exige mudança nos hábitos de vida dos pacientes. O objetivo da presente pesquisa foi analisar o perfil clínico e epidemiológico dos pacientes com diabetes mellitus tipo 2 assistidos pelo Componente Especializado da Assistência Farmacêutica do estado do Piauí. Trata-se de uma pesquisa descritiva, de caráter transversal com análise de variáveis sociais, demográficas e econômicas e de parâmetros bioquímicos e antropométricos. Dentre 93 participantes, 66,7% eram do sexo feminino, 57% possuíam média etária de 60,5 anos e 50,5% apresentaram peso acima de 69 kg com renda familiar preponderante de um salário mínimo e grau de escolaridade referente ao ensino médio completo. Constatou-se que 53,8% dos participantes praticavam atividade física regularmente e 87,1% faziam restrição alimentar. O medicamento mais utilizado foi a vildagliptina. Foi evidenciado que 52,7% possuíam controle glicêmico insatisfatório quanto aos níveis de HbA1c, assim como a necessidade da existência de um protocolo clínico estadual público que regulamente a dispensação de hipoglicemiantes orais no estado.

Seguimento farmacoterapêutico de pacientes em tratamento com talidomida em um centro especializado em hanseníase / Pharmacotherapeutic follow-up of patients treated with thalidomide at a specialized leprosy center

OBJETIVOS: Avaliar a farmacoterapia de pacientes com reação hansênica tipo 2 em tratamento com talidomida em um centro filantrópico de atendimento especializado. MÉTODOS: O estudo foi realizado no Centro Maria Imaculada de reabilitação de pacientes com hanseníase na cidade de Teresina, Piauí. Foram incluídos na pesquisa pacientes de ambos os sexos atendidos entre setembro e novembro de 2016. O Seguimento Farmacoterapêutico foi fundamentado no Método Dáder, na base eletrônica Drugdex System ­ Thomson Micromedex® ­ Interactions para análise de interações medicamentosas; na classificação de reações adversas a medicamentos de Rawlins e Thompson; e no teste de Morisky-Green para avaliar o nível de adesão terapêutica. RESULTADOS: Foram acompanhados 11 pacientes, dos quais oito eram homens. Foram identificadas três interações medicamentosas, sendo duas classificadas em risco moderado e uma em menor risco. Foram identificados 23 resultados negativos associados ao medicamento, destacando-se insegurança não quantitativa e problemas de saúde não tratados. Além disso, 22 problemas relacionados com medicamentos foram identificados, sendo o mais frequente a ocorrência de reações adversas a medicamentos. Todas as reações adversas associadas a medicamentos foram classificadas como tipo A ou previsíveis. Quanto à adesão, seis entre os nove pacientes que responderam ao teste de Morisky-Green obtiveram alto grau de adesão. A educação em saúde correspondeu à intervenção farmacêutica preponderante, sendo aplicada a todos os pacientes. CONCLUSÕES: Foram evidenciadas interações medicamentosas relevantes, resultados negativos associados ao medicamento e problemas associados a medicamentos. O grau de adesão ao tratamento com talidomida foi considerado alto. Foram necessárias intervenções farmacêuticas, sobretudo voltadas para ações de educação em saúde, o que ratifica a necessidade de acompanhamento constante desse grupo de pacientes.

AIMS: Evaluate the pharmacotherapy of patients with type 2 leprosy reaction in treatment with thalidomide in a philanthropic center of specialized care at Teresina. METHODS: The study was conducted at the Centro Maria Imaculada, for rehabilitation of patients with leprosy, in the city of Teresina, Piauí, Brazil. Patients of both sexes attended between september and november 2016 were included in the study. Pharmacotherapeutic follow-up was based on the Dáder Method, in the electronic base Drugdex System ­ Thomson Micromedex® ­ Interactions for analysis of drug interactions; in the classification of adverse drug reactions of Rawlins and Thompson; and the Morisky-Green test to evaluate the level of therapeutic adherence. RESULTS: Eleven patients were followed, of whom eight were male. Three drug interactions were identified, two of which were classified as moderate risk and one in lower risk. There were 23 negative results associated with medicines, mainly quantitative insecurity and untreated health problems. In addition, 22 drug-related problems were identified, with adverse drug reactions being the most frequent occurrence. All adverse drug reactions were classified as type A or predictable. Regarding adhesion, six patients among nine who responded to the Morisky-Green test obtained a high degree of adhesion. Health education corresponded to the preponderant pharmaceutical intervention, being applied to all patients. CONCLUSIONS: Relevant drug interactions, negative results associated with medicines, and drug-related problems were identified. Degree of adherence to thalidomide treatment was considered high. Pharmaceutical interventions were necessary, mainly focused on health education actions, which ratifies the need for constant monitoring of this group of patients.

Behavioral effects induced by antitumor cleronade diterpenes from Casearia sylvestris and in silico interactions with neuron receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris is a medicinal plant traditionally used to treat snakebites, wounds, inflammation and gastric ulcers and scientific supports for have demonstrated its antitumor, antihyperlipidemic and antiparasitic properties. AIM OF THE STUDY: To assess the effects of a fraction with casearins (FC) on adult mice using classical experimental models of animal behavior and theoretical calculations to verify the interaction of Casearin X (Cas X) with neuron receptors. MATERIALS AND METHODS: Animals divided in 6 groups (n=9/group) were intraperitoneally treated with vehicle (DMSO 4%), FC (2.5, 5, 10 and 25mg/kg/day) and diazepam (2mg/kg) for 7 days. Thirty minutes after the last dose of treatment, acute toxicity and behavioral experiments were performed. RESULTS: The highest dose of FC (25mg/kg/day) caused diarrhea, weight loss and death of one animal. Elevated plus maze test showed that lower doses [2.5mg/kg/day (36.4±5.1s) and 5mg/kg/day (43.9±6.2s)] increased the time spent in open arms (TSOA). Open field test revealed reduction in the number of crossings (54.9%, 51.1%, 48% and 67.7% for 2.5, 5, 10 and 25mg/kg/day, respectively) in all doses of FC studied and decrease of rearings at 25mg/kg/day (p<0.05). Computational calculations showed that the inhibition constant (Ki) for the Cas X-D1 complex is up to 1000-fold more favourable than the Cas X-GABAA complex. All ∆G° values obtained for Cas X-D1 complexes were more negative than those seen with Cas X-GABAA complexes. CONCLUSIONS: Findings indicate a probable anxiolytic action of the FC since it reduces the number of crossings and rearings and prolonged the time spent in open arms, without sedative and myorelaxant effects, probably due to the interaction of Cas X with dopaminergic system.

In vitro antioxidant, antitumor and leishmanicidal activity of riparin A, an analog of the Amazon alkamides from Aniba riparia (Lauraceae) / Atividade antioxidante, antitumoral e leishmanicida in vitro da riparina A, um análogo das alcamidas amazônicas de Aniba riparia (Lauraceae)

Aniba riparia (Lauraceae) is an important medicinal plant found in the Amazon region and presents alkaloids of the type alkamide known as riparins. Riparin A is structurally represented as the fundamental core of all Amazon riparins. This work aimed to assess the in vitro antioxidant, antitumor and antileishmanial effects of riparin A. Riparin A presented weak antioxidant capacity by tecniques of DPPH• (EC50 of 296.2 μg mL-1) and ABTS•+ (EC50 of 450.1 μg mL-1), showed moderate activity against colon carcinoma (HCT-116: IC50 of 21.7 μg mL-1) and leishmanicidal activity on promastigotes of L. amazonensis (IC50 of 307.0 ± 79.6, 193.7 ± 44.3 and 81.8 ± 11.2 μg mL-1, respectively, after 24, 48 and 72 h of incubation). Then, in addition to its structural simplicity, riparin A revealed promising biological activities and remarkable in vitro leishmanicidal action, an important result in epidemiological point of view to control leishmaniasis in Brazil, including in the Amazon region.

Aniba riparia (Lauraceae) é uma importante planta medicinal encontrada na região amazônica que apresenta alcaloides do tipo alcamida e conhecidos como riparinas. Este trabalho teve como objetivo avaliar os efeitos antioxidantes, antitumorais e leishmanicidas in vitro da riparina A. Riparina A apresentou fraca capacidade antioxidante pelas técnicas do DPPH• (CE50 de 296,2 μg mL-1) e ABTS•+ (CE50 de 450,1 μg mL-1), mostrou moderada atividade contra carcinoma de cólon (HCT-116: CI50 de 21,7 μg mL-1) e atividade leishmanicida sobre formas promastigotas de Leishmania amazonensis (CI50 de 307,0 ± 79,6; 193,7 ± 44,3 e 81,8 ± 11,2 μg mL-1, respectivamente, após 24, 48 e 72 h de incubação). Assim, além de sua simplicidade estrutural, a riparina A revelou atividades biológicas promissoras e significativa ação leishmanicida in vitro, resultado importante diante da relevância epidemiológica para controle da leishmaniose no Brasil, inclusive na região amazônica.