RESUMEN
Though traditional medicines have been developed through practice for thousands of years, limited research has discussed the research and development (R&D) pattern of traditional medicines. China's discovery of artemisinin accumulated valuable experiences to explore traditional medicine under low-resource settings. With limited R&D resources, China mobilized all domestic research units at different levels and departments to develop artemisinin collaboratively. The discovery of artemisinin not only based on valuable experiential wisdom of traditional medicine, but also relied on excellent synergy among all units. In this study, we reviewed the story of how artemisinin was discovered in China, summarized key factors for new drug development from traditional medicines under limited resources, and raised suggestions to utilize traditional medicines in low- and middle-income countries. This case suggested that the vitality of traditional medicine could be extended by promoting new drug development based on modern methods and collaboration.
Asunto(s)
Artemisininas , Países en Desarrollo , China , Medicina Tradicional , InvestigaciónRESUMEN
Pueraria lobata is utilized as a food source in China. The aim of this study is to combine virtual screening and molecular dynamics predictive model to screen out the potential synaptic plasticity-maintaining components from the root of P. lobate and to verify it by employing the amyloid ß-injected rats' model. Eighteen compounds were identified by HPLC-MS/MS; puerarin manifested the most potential to form a stable complex with calcium/calmodulin kinase IIα (CaMK IIα), which is the key protein in synaptic plasticity by the in silico study. The further in vivo assay showed that puerarin could elevate the synaptic thickness, density, and length, relieve calcium overload, regulate the expression of CaMK IIα, and other p38MAPK-CREB signaling pathway-related biochemical criteria. The behavioral test also verified the results. Results have confirmed that the root of P. lobate can work anti-AD by maintaining the synaptic plasticity and proved the reliability of using the in silico predictive model to determine active ingredients from the natural product.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Productos Biológicos/farmacología , Simulación del Acoplamiento Molecular , Plasticidad Neuronal/efectos de los fármacos , Raíces de Plantas/química , Pueraria/química , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Animales , Productos Biológicos/química , Calcio/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Hipocampo/citología , Hipocampo/efectos de los fármacos , Humanos , Isoflavonas/química , Isoflavonas/farmacología , Neuronas/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Proteínas/genética , Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
The root of Pueraria lobata has been utilized as a food source for thousands of years in China. Puerarin is the major bioactive and the most abundant secondary metabolite obtained from the root of P. lobata. The potential therapeutic effect of puerarin against Alzheimer's disease was screened by in silico methods and confirmed by the amyloid ß-peptide-induced Alzheimer's disease (AD) rat model. The in silico study displayed that puerarin had the potential to penetrate across the blood-brain barrier and had high stability in molecular docking and dynamics simulation with acetylcholinesterase (AChE), cyclooxygenase-2 (COX-2) and caspase-3 (C3), which play a central role in the development of AD. The in vivo results showed that puerarin could restrain the AChE activity, restore the activities of antioxidant defense substances toward normal levels, and decrease the expression of inflammatory factors and apoptosis genes in the brain, especially down-regulating the expressions of COX-2 and C3. The histopathological examination of brain sections and behavioral testing also verified the biochemical observations, which further validates the in silico study. These results not only suggest that puerarin, as a potential compound, could relieve AD, but also broaden the applications of puerarin.