ABSTRACT
This review presents a historical overview of drug discovery and the non-clinical stages of the drug development process, from initial target identification and validation, through in silico assays and high throughput screening (HTS), identification of leader molecules and their optimization, the selection of a candidate substance for clinical development, and the use of animal models during the early studies of proof-of-concept (or principle). This report also discusses the relevance of validated and predictive animal models selection, as well as the correct use of animal tests concerning the experimental design, execution and interpretation, which affect the reproducibility, quality and reliability of non-clinical studies necessary to translate to and support clinical studies. Collectively, improving these aspects will certainly contribute to the robustness of both scientific publications and the translation of new substances to clinical development.
Subject(s)
Animals , Computer Simulation , Drug Discovery , Drug Evaluation, Preclinical/methods , Computer-Aided Design , Models, Animal , Reproducibility of ResultsABSTRACT
RESUMO: Objetivou-se com este trabalho avaliar a produção de massa e o teor de flavonoides de plantas de marcela cultivadas com fósforo e cama de frango e colhidas em duas épocas. Estudou-se a combinação de doses de P2O5 (0, 100, 200 e 300 kg ha-1) na forma de superfosfato triplo, com e sem cama de frango (10 t ha-1), arranjados como fatorial 4x2, no delineamento blocos casualizados, com quatro repetições. Foram feitas duas colheitas das plantas, consideradas como parcelas subdivididas no tempo. A propagação foi indireta, com semeio em bandejas e transplante ao campo. As plantas foram colhidas aos 195 e 223 dias após o transplantio - DAT. A altura máxima das plantas foi de 1,14 m com uso da cama de frango e de 0,97 m sem cama, aos 195 dias após o transplantio. A produção máxima de massa fresca de parte aérea das plantas foi de 30,31 t ha-1 na colheita aos 223 DAT, enquanto a de massa seca foi de 11,38 t ha-1, ambas com o uso de 300 kg ha-1 de P2O5.A massa fresca de inflorescências foi maior (4,08 t ha-1) com adição de cama de frango ao solo e menor (3,49 t ha-1) sem cama de frango; em resposta às doses de fósforo, cresceram linearmente, sendo a máxima de 4,65 t ha-1 com uso de 300 kg ha-1 de P2O5, independente da época de colheita. A massa seca de inflorescências foi máxima de 2,38 t ha-1 com o uso de 300 kg ha-1 P2O5 na colheita aos 223 DAT. A maior produção de massa seca e o maior teor de flavonoides das inflorescências foram obtidos com o cultivo das plantas de marcela em solo com cama de frango (10 t ha-1) e com P2O5 (300 kg ha-1) na colheita aos 223 dias após o transplantio.
ABSTRACT: The aim of this experiment was to evaluate the biomass yield and flavonoid contents of Achyrocline satureioides grown under different levels of phosphate fertilizer in association with broiler litter, during two successive harvests. Four levels of P2O5 (0, 100, 200 and 300 kg ha-1), as triple superphosphate, and two levels of broiler litter (0 and 10 t ha-1) were arranged as a 4x2 factorial design in randomized blocks with four replications. Two harvests of plants, considered as split-plot, were made. Seeds were sown in polystyrene trays then transplanted to the experimental field and harvested at 195 and 223 days after transplanting (DAT). The maximum heights of the plants were 1.14 m under the addition of broiler litter and 0.97 m without it, at 195 days after transplanting. The highest yields of total fresh weight (30.31 ton ha-1) and dry weight (11.38 ton ha-1) were obtained at 223 DAT, both with the concentration of 300 kg ha-1 P2O5. The fresh weight of the inflorescences was greater under the addition of broiler litter (4.08 ton ha-1) than without it (3.49 ton ha-1). The plants grew linearly in response to the use of phosphate, and the maximum yield was 4.65 ton ha-1 under the concentration of 300 kg ha-1 P2O5, regardless of the harvest season. The dry weight of the inflorescences reached maximum yield (2.38 ton ha-1) at 223 DAT, in response to the use of 300 kg ha-1 P2O5. The highest yield of dry weight and the highest contents of flavonoids from the inflorescences were obtained when A. satureioides was grown under the concentration of P2O5 (300 kg ha-1) with the addition of broiler litter (10 ton ha-1) and harvested at 223 DAT.
Subject(s)
Flavonoids/analysis , Achyrocline/anatomy & histology , Phosphorus/pharmacology , Plants, Medicinal/classificationABSTRACT
The growing trade market in herbal medicines is aworldwide phenomenon due to several factors, fromthe high cost of manufactured drugs to mere fashion.In this study, we tested the quality of pharmaceuticalproducts based on Hypericum perforatum L. (Eng. ?StJohn?s Wort?) marketed in Divinópolis City, State ofMinas Gerais, Brazil. Samples of products labeled H.perforatum were purchased at three commercial stores,at various times during one year. We assessed thefollowing items: pharmacobotanical characteristics,humidity, total ash, hypericin content and thin layerchromatographic profile. Close inspection showed that4 of the 12 samples sold as H. perforatum products werefrom a different plant from that advertised, representinga forgery in which the true species was replaced byAgeratum sp. Besides, the samples did not entirely meetthe legal requirements for herbal medicine. Therefore,there is a need to strengthen pharmaceutical vigilance,to ensure that herbal products are suitable for publicuse.
O crescente comércio de plantas medicinais e fitoterápicos ocorre em todo o mundo em razão de diversos fatores, como o alto custo dos medicamentos industrializados ou modismo. Neste trabalho verificou-se a qualidade de produtos farmacêuticos contendo Hypericum perforatum L. comercializados em Divinópolis, Minas Gerais, Brasil. Adquiriram-se amostras de H. perforatum em três estabelecimentos distintos em diferentes épocas ao longo de um ano. Avaliaram-se os seguintes itens: aspectos farmacobotânicos, umidade, cinzas totais, doseamento de hipericina e cromatografia em camada delgada. Os resultados demonstraram que quatro amostras comercializadas como H. perforatum eram produtos diferentes daqueles anunciados, caracterizando uma falsificação e substituição da espécie verdadeira por Ageratum sp. Além disso, as amostras não cumpriram totalmente os requisitos exigidos pela legislação. Portanto, faz-se necessário reforçar a vigilância farmacêutica, buscando garantir produtos de qualidade adequados ao uso da população.