Resumen
Objetivo: Simular análisis farmacocinéticos y farmacodinámicos de la quercetina, utilizando métodos in sílico y reportar su efecto en el combate de la hiperglucemia, a través de una revisión de la literatura. Métodos: Estudio mixto, descriptivo-exploratorio y transversal. Los datos se recopilaron en las plataformas Swiss ADME y Swiss Target Prediction, ambas disponibles en línea y gratis. En ellos se realizaron análisis farmacocinéticos, incluida la interacción con las enzimas del citocromo P450 y se evaluaron las propiedades farmacodinámicas, con la predicción de dianas biológicas, respectivamente. Se utilizaron las bases de datos Pubmed y Google Scholar para realizar una investigación bibliográfica analítica sobre el potencial terapéutico de la quercetina en la Diabetes Mellitus tipo 2 (DM2). Resultados: Se demostró buena biodisponibilidad oral, cumpliendo los parámetros de la Regla de Lapinsk. Mostró resultados prometedores en parámetros farmacocinéticos, aunque presentó un efecto inhibidor sobre las proteínas CYP1A2, CYPD6 y CYP3A4. Interactuó con 100 objetivos biológicos: 33,3% quinasa, 6,7% liasa, 6,7% proteasa, 6,7% citocromo P450, 13,3% receptor acoplado a proteína G, 13,3% enzima y 20% oxidorreductasa. Conclusión: Se concluyó el potencial de la quercetina para el desarrollo de nuevos fármacos hipoglucemiantes, pero se requieren más estudios para evaluar su eficacia y seguridad.
Referencias
ALKHALIDY H, et al. Kaempferola meliorates hyperglycemia through suppressing hepatic gluconeogenesis and enhancing hepatic insulin sensitivity in diet-induced obesity mice. J Nutr Biochem, 2018; 90-101.
ANKER JVD, et al. Developmental Changes in Pharmacokinetics and Pharmacodynamics. J Clin Pharmacol, 2018; S10-S25.
BHATTACHARYA S, et al. Caffeic acid, naringenin and quercetinenhance glucose-stimulated insulin secretion and glucose sensitivity in INS-1E cells. Diabetes Obes Metab, 2003; 602-612.
CAIA NARRA e DE FREITAS JCR. Avaliação das propriedades farmacocinéticas de um candidato a fármaco derivado da d-glicose. CONIMAS, 2019.
CHEN S, et al. Therapeutic Effects of Quercetin on Inflammation, Obesity, and Type 2 Diabetes. Inflammatory mediators, 2016; 1-5.
DARENSKAYA MA, et al. Oxidative stress: pathogenetic role in diabetes mellitus and its complications and therapeutic approaches to correction. Bulletin of experimental biology and medicine, 2021; 171(2): 179-189.
EID HM e HADDAD PS. The Antidiabetic Potential of Quercetin: Underlying Mechanisms. Current medicinal chemistry, 2017; 24(4): 355-364.
EL KHOURY G, et al. Prevalence, Correlates and Management of Hyperglycemia in Diabetic Non-critically Ill Patients at a Tertiary Care Center in Lebanon. Current diabetes reviews, 2019; 15(2): 133-140.
GRAF AB, et al. Rat Gastrointestinal Tissues Metabolize Quercetin. The Journal of Nutrition, 2006; 39-44.
GUPTA P, et al. Emerging role of protein kinases in diabetes mellitus: From mechanism to therapy. Advances in protein chemistry and structural biology, 2021; 124: 47-85.
GUYOMARD V, MYINT PK. Optimum control of blood glucose for prevention and treatment of ischemic and hemorrhagic stroke. Current treatment options in cardiovascular medicine, 2009; 11(3): 201-11.
HAWKINS BT e DAVIS TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacological reviews, 2005; 173-185.
LI Y, et al. Quercetin, Inflammation and Immunity. Nutrients, 2016; 8(3): 167.
LIN K, et al. An Interpretable Double-Scale Attention Model for Enzyme Protein Class Prediction Based on Transformer Encoders and Multi-Scale Convolutions. Frontiers in genetics, 2022; 1-20.
LUCAS V, et al. Bioactivity of dietary polyphenols: The role of metabolites. Critical Reviews in Food Science and Nutrition, 2019; 1-35.
MIRZAEI M. Ciência e engenharia in silico. Adv J Sci Eng, 2020; 1(1): 1-2.
MOHO SV, et al. Inhibitory effects of quercetin and its main methyl, sulfate, and glucuronic acid conjugates on cytochrome P450 enzymes, and on OATP, BCRP and MRP2 transporters. Nutrients, 2020; 12(8): 2306.
OHDY e OLEFSKY JM. G protein-coupled receptors as targets for antidiabetic therapeutics. Nature reviews Drug discovery, 2016; 15(3): 161-172.
OLTHOF MR, et al. Bioavailabilities of quercetin-3-glucoside and quercetin-4'-glucoside do not differ in humans. Human Nutrition and Metabolism—Research Communication, 2000; 1200-1203.
OTEIZA PI, et al. Flavonoids and the gastrointestinal tract: Local and systemic effects. Molecular Aspects of Medicine, 2018; 41-49.
PAN D, et al. The role of protein kinase C in diabetic microvascular complications. Frontiers in Endocrinology, 2022; 13: 973058.
PARDO MR, et al. Bioavailability of magnesium food supplements: A systematic review. Nutrition, 2021; 111294.
PATEL RV, et al. Therapeutic potential of quercetin as a cardiovascular agent. European Journal of Medicinal Chemistry, 2018; 889-904.
PATEL R, et al. Pharmaceutical Excipients and Drug Metabolism: A Mini-Review. Int J Mol Sci, 2020; 1-21.
POET TS e MCDOUGAL JN. Skin absorption and human risk assessment. Chem Biol Interact, 2002; 19–34.
RODRIGUES GS, et al. Uso de softwares livres em aula prática sobre filtros moleculares de biodisponibilidade oral de fármacos. Química Nova, 2021; 44: 1036-1044.
SERRA CA, et al. Quercetin prevents insulin dysfunction in hypertensive animals. J Diabetes Metab Disord., 2022, 408-417.
SIDHU JS, et al. Trends in small organic fluorescent scaffolds for detection of oxidoreductase. Biosens Bioelectron, 2021; 113441.
TSAO JP, et al. Short-Term Oral Quercetin Supplementation Improves Post-exercise Insulin Sensitivity, Antioxidant Capacity and Enhances Subsequent Cycling Time to Exhaustion in Healthy Adults: A Pilot Study. Front Nutr, 2022; 9: 1-5.
VAN DE WATERBEEMDH e GIFFORDE. ADMET in silico modelling: towards prediction paradise? Nat Rev Drug Discov., 2003; 2(3): 192-204.
WANG Y e MA H. Protein kinase profiling assays: a technology review. Drug Discov Today Technol, 2015; 1-8.
WEIS WI e KOBILKA BK. The Molecular Basis of G Protein–Coupled Receptor Activation. Annu Rev Biochem, 2018; 897-919.
XIE J, et al. Nanomaterial-based blood-brain-barrier (BBB) crossing strategies. Biomaterials, 2019; 1-20.
