RESUMO
Muscle fatigue is induced by an acute or chronic physical performance inability after excessive physical activity often associated with lactate accumulation, the end-product of glycolysis. In this study, the water-extracted roots of Sanguisorba officinalis L., a herbal medicine traditionally used for inflammation and diarrhea, reduced the activities of lactate dehydrogenase A (LDHA) in in vitro enzyme assay myoblast C2C12 cells and murine muscle tissue. Physical performance measured by a treadmill test was improved in the S. officinalis-administrated group. The analysis of mouse serum and tissues showed significant changes in lactate levels. Among the proteins related to energy metabolism-related physical performance, phosphorylated-AMP-activated protein kinase alpha (AMPKα) and peroxisome proliferator-activated receptor-coactivator-1 alpha (PGC-1α) levels were enhanced, whereas the amount of LDHA was suppressed. Therefore, S. officinalis might be a candidate for improving physical performance via inhibiting LDHA and glycolysis.
Assuntos
Lactato Desidrogenase 5/antagonistas & inibidores , Desempenho Físico Funcional , Extratos Vegetais/administração & dosagem , Plantas Medicinais/química , Sanguisorba/química , Proteínas Quinases Ativadas por AMP/metabolismo , Administração Oral , Animais , Linhagem Celular , Teste de Esforço , Glicólise/efeitos dos fármacos , Ácido Láctico/metabolismo , Masculino , Medicina Tradicional Coreana , Camundongos , Camundongos Endogâmicos C57BL , Mioblastos Esqueléticos/efeitos dos fármacos , Mioblastos Esqueléticos/enzimologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Resistência Física/efeitos dos fármacos , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/química , Fitoterapia , Extratos Vegetais/químicaRESUMO
Human lactate dehydrogenase 5 (hLDH5) is an important metabolic enzyme playing critical roles in the anaerobic glycolysis. Herein, we employed an in silico method and biological validation to identify a novel hLDH5 inhibitor with a promising cellular activity under hypoxia condition. The identified compound 9 bound to hLDH5 with a Kd value of 1.02⯵M, and inhibited the enzyme with an EC50 value of 0.7⯵M. Compound 9 exhibited a weak potency against NCI-H1975 cell proliferation under normal condition (IC50â¯=â¯36.5⯵M), while dramatically increased to 5.7⯵M under hypoxia condition. In line with the observation, hLDH5 expression in NCI-H1975 cell under hypoxia condition is much higher as compared to the normal oxygenated condition, indicating the hLDH5 inhibition may contribute to the cancer cell death.