Abstract The globalization of the pharmaceutical market has enabled access to a considerable number of new medicinal products. Consequently, the circulation of substandard medicinal products has also increased. To minimize this problem, post-marketing quality sampling and testing programs are performed to monitor and confirm that the medicinal products available in the market meet appropriate quality requirements. In this review, the post-approval sampling and testing procedures of six regulatory authorities were compared with the goal of strengthening these market surveillance systems. Similarities were observed between the procedures adopted by different regulatory authorities. However, the agencies were not always transparent about the results of these monitoring procedures. A probable mismatch between the registration procedures and the quality requirements listed in official compendiums was observed, which resulted in dissonance and contradiction between the specifications approved by the regulatory authorities and those required in the pharmacopeias. Therefore, strengthening harmonization projects related to these activities can help minimize such difficulties.

Hippeastrum puniceum is a species that belongs to the Amaryllidaceae family. A particular characteristic of this family is the consistent and very specific presence of isoquinoline alkaloids, which have demonstrated a wide range of biological activities such as antioxidant, antiviral, antifungal, antiparasitic, and acetylcholinesterase inhibitory activity, among others. In the present work, fifteen alkaloids were identified from the bulbs of Hippeastrum puniceum (Lam.) Kuntz using a GC-MS approach. The alkaloids 9-O-demethyllycoramine, 9-demethyl-2α-hydroxyhomolycorine, lycorine and tazettine were isolated through chromatographic techniques. The typical Amaryllidaceae alkaloids lycorine and tazettine, along with the crude and ethyl acetate extract from bulbs of the species were evaluated for their inhibitory potential on α-amylase, α-glucosidase, tyrosinase and acetylcholinesterase activity. Although no significant inhibition activity was observed against α-amylase, α-glucosidase and tyrosinase from the tested samples, the crude and ethyl acetate extracts showed remarkable acetylcholinesterase inhibitory activity. The biological activity results that correlated to the alkaloid chemical profile by GC-MS are discussed herein. Therefore, this study contributed to the knowledge of the chemical and biological properties of Hippeastrum puniceum (Lam.) and can subsidize future studies of this species.

ABSTRACT Hippeastrum goianum (Ravenna) Meerow, Amaryllidaceae, is an endemic species from the Cerrado, Brazil; there are only few studies about its chemistry or biological activity. This study aimed to investigate the occurrence of lycorine in extracts from in vitro H. goianum plantlets, as well as evaluate a possible inhibition of acetylcholinesterase. The ethanol extract of plantlets produced by in vitro seed germination and micropropagation of bulblets was obtained from seedlings from in vitro germination, while the ethanol extract micropropagtion of bulblets was obtained from a subculture of those seedlings. The presence of lycorine was detected in only in the micropropagation of bulblets. The micropropagation of bulblets was more active than the plantlets produced by in vitro seed germination, with an IC50 of 114.8 ± 0.95 µg/ml and IC50 386.00 ± 0.97 µg/ml, respectively. These results showed that both in vitro germination and micropropagation of H. goianum can lead to the biosynthesis of lycorine. Moreover, the micropropagation led to improved anticholinesterase activity.

Abstract The Pterodon genus comprises two native species in Brazil, known as “sucupira-branca” or “faveira”. Their fruits have long been used in Brazilian natural medicine, mainly for the treatment of infections and inflammations. The pharmacological properties of these fruits have often been linked with vouacapane diterpenoids. This review evaluated the scientific research in the period from 1973 to February 2017, aiming to answer how difficult it still is to develop a scientifically supported product based on Pterodon vouacapanes. Therefore, this paper reviews purification, identification, and quantification methods applied to vouacapane diterpenoids from Pterodon, as well as the performance of these phytochemicals in pharmacological tests described in the literature. Data analysis results support conventional notions that suggest vouacapane diterpenoids from Pterodon have anti-inflammatory properties. However, the studies carried out so far still represent partial assessment of the vouacapane activities and further studies need to be completed. Pterodon diterpenoids have also been associated with larvicidal, leishmanicidal, cardiovascular, and antitumor activities, which reinforces the genus' potential as a source of phytomedicines. Some remaining gaps about the reviewed activities were mentioned, while trends and perspectives for future research were proposed.

ABSTRACT Regulatory transparency is an imperative characteristic of a reliable National Regulatory Authority. In the region of the Americas, the process of building an open government is still fragile and fragmented across various Health Regulatory Agencies (HRAs) and Regional Reference Authorities (RRAs). This study assessed the transparency status of RRAs, focusing on various medicine life-cycle documents (the Medicine Dossier, Clinical Trial Report, and Inspection Report) as tools for strengthening health systems. Based on a narrative (nonsystematic) review of RRA regulatory transparency, transparency status was classified as one of two types: public disclosure of information (intra-agency data) and data- and work-sharing (inter-agency data). The risks/benefits of public disclosure of medicine-related information were assessed, taking into account 1) the involvement and roles of multiple stakeholders (health care professionals, regulators, industry, community, and academics) and 2) the protection of commercial and personal confidential data. Inter-agency data- and work-sharing was evaluated in the context of harmonization and cooperation projects that focus on regulatory convergence. Technical and practical steps for establishing an openness directive for the pharmaceutical regulatory environment are proposed to improve and strengthen health systems in the Americas. Addressing these challenges requires leadership from entities such as the Pan American Health Organization to steer and support collaborative regional alliances that advance the development and establishment of a trustworthy regulatory environment and a sustainable public health system in the Americas, using international successful initiatives as reference and taking into account the domestic characteristics and experiences of each individual country.

RESUMEN La transparencia normativa es una característica indispensable de las autoridades de registro sanitario fidedignas. En la Región de las Américas, el proceso de crear un gobierno transparente sigue siendo frágil y fragmentado en distintos organismos de reglamentación sanitaria (ORS) y organismos de referencia regionales (ORR). En el presente estudio se examinó la transparencia de los ORR mediante el escrutinio de diferentes documentos con datos relativos al ciclo vital de los medicamentos (el expediente farmacológico, el informe de los ensayos clínicos y el informe de las inspecciones) como instrumentos para fortalecer los sistemas de salud. Sobre la base de una revisión narrativa (es decir, no sistemática) de la transparencia reglamentaria en los ORR, la situación relativa a la transparencia se clasificó en dos tipos: la divulgación pública de información (datos intrainstitucionales) y el intercambio de datos y la colaboración (datos interinstitucionales). Se evaluaron los riesgos y beneficios de la divulgación pública de información sobre medicamentos teniendo en cuenta (1) la participación y las funciones de los distintos interesados directos (profesionales de la salud, el sector industrial, la comunidad y el sector académico) y (2) la protección de los datos comerciales y personales de carácter confidencial. El intercambio de datos y la colaboración entre agencias se evaluaron en el contexto de diversos proyectos de armonización y cooperación dirigidos a lograr la convergencia reglamentaria. Se propone la toma de medidas técnicas y prácticas para establecer una directiva en pro de la transparencia en el medio reglamentario farmacéutico a fin de mejorar y fortalecer los sistemas de salud en las Américas. Hacer frente a estas dificultades exige el liderazgo de entidades como la Organización Panamericana de la Salud en la dirección y el respaldo de alianzas de colaboración regionales que fomenten el desarrollo y establecimiento de un entorno reglamentario fidedigno y de un sistema de salud pública sostenible en las Américas, usando como punto de partida las iniciativas internacionales que hayan dado buenos resultados y teniendo en cuenta las características internas y las experiencias de cada país.

Resumo O câncer de boca e de orofaringe emerge como o 6º tipo de câncer mais comum no mundo. O tratamento pode envolver cirurgia, quimioterapia e radioterapia. Mais de 50% das drogas com atividade de combate ao câncer foram isoladas de fontes naturais, tais como a Catharanthus roseus e a epipodofilotoxina, isolada de Podophyllum. O maior desafio é maximizar o controle da doença, enquanto minimiza a morbidade e toxicidade para os tecidos normais circundantes. O Erythroxylum suberosum é uma planta comum no bioma Cerrado brasileiro e é popularmente conhecida como "cabelo-de-negro". O objetivo deste estudo foi avaliar a citotoxicidade dos extratos da planta Erythroxylum suberosum do bioma Cerrado brasileiro, associados à radioterapia em linhagens celulares humanas de carcinomas de língua e de hipofaringe. As células foram tratadas com os extratos aquoso, etanólico e hexânico do Erythroxylum suberosum e irradiadas com 4 Gy, 6 Gy e 8 Gy. A citotoxidade foi avaliada pelo ensaio de MTT e a absorvância foi medida a 570 nm em uma leitora Beckman. A cisplatina, quimioterápico padrão, foi utilizada como controle positivo. O uso de extratos de Erythroxylum suberosum mostrou potencial efeito radiosensibilizante in vitro no câncer de cabeça e pescoço. O efeito da citotoxicidade nas linhagens foi de forma não seletiva e muito semelhante ao efeito da quimioterapia padrão. O extrato aquoso de Erythroxylum suberosum, combinado com radioterapia, foi o extrato mais citotóxico para os carcinomas de língua e hipofaringe, associados à radioterapia.

Abstract The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as "cabelo-de-negro". The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas.

In the field of health regulation, enabling public access to data from clinical trials is a process currently undergoing consolidation by the principal regulators worldwide. This paper discusses recent developments in public policy regarding regulatory transparency, and the risks and benefits of a regulatory impact-analysis on clinical trial reports, from the perspective of the key stakeholders (i.e., patients, prescribers, government, society, industry, and regulators). Additionally, the social, technical, and ethical aspects of the datasharing process are highlighted, including access limits, commercially-confidential data and patent rights, privacy of research subjects, arrangements and publicity tools, and clinical trials registration. Furthermore, perspectives on improvement and expansion of regulatory transparency policies are presented, contextualizing North American, Latin American, and European experiences, and highlighting in-teragency cooperation and collaboration initiatives that aim to harmonize health programs and regulatory convergence.

En el campo de la reglamentación sanitaria, la habilitación del acceso público a los datos de los ensayos clínicos constituye un proceso actualmente en fase de consolidación por parte de los principales reguladores a escala mundial. Este artículo trata sobre los recientes avances en las políticas públicas con respecto a la transparencia reglamentaria, y los riesgos y beneficios de un análisis reglamentario de la repercusión en los informes de los ensayos clínicos desde la perspectiva de los interesados directos clave (es decir, los pacientes, los prescriptores, el gobierno, la sociedad, la industria y los organismos reguladores). Por otra parte, se destacan los aspectos sociales, técnicos y éticos del proceso del uso compartido de datos, incluidos los límites de acceso, los datos comercialmente confidenciales y los derechos de patente, la privacidad de los sujetos sometidos a investigación, los acuerdos y las herramientas publicitarias, y el registro de los ensayos clínicos. Además, se muestran las perspectivas en materia de mejora y ampliación de las políticas de transparencia reglamentaria, contextualizando las experiencias norteamericanas, latinoamericanas y europeas, y destacando la cooperación interinstitucional y las iniciativas de colaboración dirigidas a la armonización de los programas de salud y a la convergencia reglamentaria.

Proteases hydrolyze the peptide bonds of proteins into peptides and amino acids, being found in all living organisms, and are essential for cell growth and differentiation. Proteolytic enzymes have potential application in a wide number of industrial processes such as food, laundry detergent and pharmaceutical. Proteases from microbial sources have dominated applications in industrial sectors. Fungal proteases are used for hydrolyzing protein and other components of soy beans and wheat in soy sauce production. Proteases can be produced in large quantities in a short time by established methods of fermentation. The parameters such as variation in C/N ratio, presence of some sugars, besides several other physical factors are important in the development of fermentation process. Proteases of fungal origin can be produced cost effectively, have an advantage faster production, the ease with which the enzymes can be modified and mycelium can be easily removed by filtration. The production of proteases has been carried out using submerged fermentation, but conditions in solid state fermentation lead to several potential advantages for the production of fungal enzymes. This review focuses on the production of fungal proteases, their distribution, structural-functional aspects, physical and chemical parameters, and the use of these enzymes in industrial applications.

The use of medicinal plants in Brazil is widespread and is supported by public policies; it has the objective of providing the population with safe and effective herbal medicines of adequate quality. An action in these policies is to develop medicinal plant monographs to gather published information and decide which medicinal plants should be financed by the Brazilian government and distributed by the public health system. Currently, the monographs published worldwide do not present unified information regarding medicinal plants, and generally, they do not cover enough requirements for herbal medicine registration. The aim of this study is to develop a monograph model with standardized information not only about botany, agronomy, quality control, safety, and efficacy but also about relating regulatory aspects that support herbal medicine regulation. The development of standardized monographs favors the fast authorization and distribution of herbal medicines in the public system. The model also points out the lacking studies that should be carried out to supplement the necessary regulatory information of medicinal plants.

Introduction: Tabernaemontana solanifolia A. DC. (Apocynaceae) grows in the Cerrado (savanna), Caatinga (shrublands), and Atlantic Forest of Brazil. Objective: to investigate the potential anxiolytic activity of the crude extracts and ß-amyrin acetate obtained from the leaves of Tabernaemontana solanifolia in the elevated plus-maze (EPM) test for anxiety in rats. Methods: the crude extracts (aqueous, ethanol, and hexane), as well as ß-amyrin acetate, obtained from Tabernaemontana solanifolia leaves were evaluated for possible anxiolytic effects in rats tested in the elevated plus-maze. Acute toxicity in rats was determined by OECD 423 guidelines. The leaves of T. solanifolia specimens collected in Brasília, Brazil, were air dried at 40 °C and macerated with hexane or ethanol. After filtration, the solvents were removed under reduced pressure, yielding the crude hexane and ethanolic extracts (5.96 and 18.62 % yield, respectively). The crude aqueous extract was obtained by infusion, followed by lyophilization (13.5 % yield). Thirty minutes before the elevated plus-maze experiments, the animals were treated with the crude ethanol extract (1 000 mg/kg of body weight [bw], p.o.), the crude hexane extract (1 000 mg/kg bw, p.o.), the crude extract (1 000 mg/kg bw, p.o.), or ß-amyrin acetate (21 mg/kg bw, p.o.). Results: the extracts cauded no mortality up to 2 000 mg/kg, so half of DL50 doses were selected for the present study. The crude extracts (hexane, ethanolic and aqueous) (1.0 g/kg) as well as the substance ß-amyrin acetate (21 mg/kg) were administered once, increasing the number of entries into and the time spent in the closed arms of the elevated plus-maze. Conclusion: the oral administration of the extracts and ß-amyrin acetate obtained from Tabernaemontana solanifolia had an anxiogenic effect in rats. Further studies are needed in order to identify and characterize the anxiogenic properties of Tabernaemontana solanifolia and to understand the anxiogenic mechanisms of the extracts.

Introducción: Tabernaemontana solanifolia A. DC. (Apocynaceae) crece en el Cerrado (sabana), Caatinga (matorrales) y la Mata Atlántica de Brasil. Objetivo: investigar la posible actividad ansiolítica de los extractos crudos y el acetato de ß-amirina obtenidos de las hojas de Tabernaemontana solanifolia en la prueba del laberinto elevado en cruz (EPM) para la ansiedad en ratas. Métodos: los extractos crudos (etanol acuoso y hexano), así como el acetato de ß-amirina, se evaluaron para posibles efectos ansiolíticos en ratas mediante la prueba del laberinto elevado en cruz. La toxicidad aguda en ratas se determinó por las directrices OCDE 423. Las hojas de Tabernaemontana solanifolia se secaron al aire a 40 °C y fueron maceradas con hexano y etanol. Después de la filtración, los disolventes se eliminaron bajo presión reducida, produciendo los extractos crudos hexano y etanólico (5,96 y 18,62 % de rendimiento, respectivamente). El extracto acuoso bruto se obtuvo por infusión, seguida por liofilización (13,5 % de rendimiento). A 30 min antes de los experimentos de laberinto elevado en cruz, los animales se trataron con el extracto de etanol crudo (1 000 mg/kg de peso corporal [bw], p.o.), el extracto de hexano crudo (1 000 mg/kg de peso corporal, por vía oral), el extracto acuoso (1 000 mg/kg de peso corporal, por vía oral) o ß-amirina acetato (21 mg/kg de peso corporal, por vía oral). Resultados: los extractos no produjeron mortalidad hasta 2 000 mg/kg, por lo que para el presente estudio se seleccionó la mitad de la dosis DL50. Los extractos crudos (hexano, etanol y acuoso) (1 000 mg/kg), así como la sustancia acetato de ß-amirina (21 mg/kg) se administraron una vez, aumentando el número de entradas y el tiempo pasado en los brazos cerrados de la prueba del laberinto elevado en cruz. Conclusión: la administración oral de los extractos y el acetato de ß-amirina obtenidos de Tabernaemontana solanifolia tuvo un efecto ansiogénico en ratas. Se necesitan estudios adicionales para identificar y caracterizar las propiedades ansiogénicas de Tabernaemontana solanifolia y para entender los mecanismos ansiogénicos de los extractos.

Em 2006, dois importantes documentos foram publicados no Brasil: a Política Nacional de Práticas Integrativas e Complementares (PNPIC) no Sistema Único de Saúde (SUS) e a Política Nacional de Plantas Medicinais e Fitoterápicos (PNPMF) à luz das quais a ANVISA avaliou as normas para o setor. Como produto dessa avaliação, foram republicadas as normas para registro de medicamentos fitoterápicos, por meio da Resolução de Diretoria Colegiada (RDC) 14/10, as Boas Práticas de Fabricação e Controle de medicamentos na indústria farmacêutica, RDC 17/10, e a lista de referências para comprovação da segurança e eficácia de medicamentos fitoterápicos, na forma da Instrução Normativa (IN) 05/10. Em relação às normas anteriormente vigentes, foram atualizados os requisitos para comprovação da segurança e eficácia destes medicamentos e sugeridas alternativas ao controle da qualidade de cada etapa de produção. Dessa forma, essa revisão tem por objetivo apresentar tais normas destacando suas características principais.

The National Policy of Integrative and Complementary Practices (PNPIC) in the Brazilian Unified Health System (SUS), and The National Policy of Medicinal Plants and Herbal Medicines (PNPMF) were launched in 2006. Based on these, the Brazilian Health Surveillance Agency (ANVISA) re-edited rules related to herbal medicines such as the Guideline to herbal medicine registration (RDC 14/10), the Good Manufacture Practices Guideline (RDC 17/10) and the List of references to assess the safety and efficacy of herbal medicines (IN 05/10). The requisites to prove herbal medicine's safety and efficacy were updated. Therefore, this review aims at presenting and commenting these new rules.

O gênero Pouteria pertence à família Sapotaceae e pode ser encontrado em muitos continentes. As plantas desse gênero têm sido utilizadas na construção civil, na alimentação e também na medicina popular. Algumas atividades biológicas são reportadas às espécies desse gênero, tais como, antioxidante, anti-inflamatória, antibacteriana e antifúngica, mas seu real potencial como fonte de novos fármacos ainda é pouco conhecido. Assim, uma revisão sobre a composição química e as atividades biológicas de Pouteria é apresentada, com o intuito de estimular a continuação dos estudos das espécies aqui citadas, e a investigação de outras espécies para as quais não foram encontrados relatos.

The genus Pouteria belongs to the family Sapotaceae and can be widely found around the World. These plants have been used as building material, as food, because the eatable fruits, as well as remedies in folk medicine. Some biological activities have been reported to species of this genus such as antioxidant, anti-inflammatory, antibacterial and antifungal. However, the real potential of this genus as source of new drugs or phytomedicines remains unknown. Therefore, a review of the so far known chemical composition and biological activities of this genus is presented to stimulate new studies about the species already reported moreover that species have no reference about chemistry or biological activities could be found until now.

Os extratos etanólicos de plantas medicinais utilizadas por moradores da cidade de Governador Valadares foram avaliados quanto às atividades antimicrobiana e citotóxica. A pesquisa de campo foi realizada durante o período de 1997-2000, por meio de entrevistas com os raizeiros locais. Foram avaliados 33 extratos brutos de um total de 32 espécies. Desses extratos, dez apresentaram toxicidade às larvas de Artemia salina (DL50<1000 ppm): Costus pisonis, Cymbopogon nardus, Eclipta alba, Eleutherine bulbosa, Erigium foetidium, Euphorbia tirucalli, Mikania hirsutissima, Momordica charantia, Solidago microglossa e Plectranthus ornatus. Quanto à atividade antimicrobiana, nenhum dos extratos apresentou atividade contra Escherichia coli. Entretanto, treze extratos mostraram-se ativos contra Staphylococcus aureus: E. alba, Scoparia sp., Arctium lappa, Chammomila tinctoria, E. bulbosa, M. hirsutíssima, S. microglossa, Stachytarpheta dichotoma, Pffafia glomerata, Stenorrhyrchnus lanceolatum, Vernonia condensata e Lippia alba.

Ethanol extracts from medicinal plants commonly used by Governador Valadares people were tested for antimicrobial activity and cytotoxicity (BST assay). The field survey was conducted during the years 1997-2000 by means of direct interviews with healing men ("raizeiros") who showed familiarity with local used remedies. A total of 33 crude extracts from 32 plant species was studied. Ten extracts (Costus pisonis, Cymbopogon nardus, Eclipta alba, Eleutherine bulbosa, Erigium foetidium, Euphorbia tirucalli, Mikania hirsutissima, Momordica charantia, Solidago microglossa and Plectranthus ornatus) presented brine shrimp toxicity (LD50<1000 ppm). Thirteen extracts presented antimicrobial activity against Staphylococcus aureus: E. alba, Scoparia sp., Arctium lappa, Chammomila tinctoria, E. bulbosa, M. hirsutíssima, S. microglossa, Stachytarpheta dichotoma, Pffafia glomerata, Stenorrhyrchnus lanceolatum, Vernonia condensata and Lippia alba. None extract presented activity against Escherichia coli.