RESUMO
Syzygium tetragonum Wall is a Chinese folk medicine for the treatment of rheumatism, joint swelling and pain. By High Content Screening (HCS), 8 compounds (1-8) from Syzygium tetragonum Wall were evaluated for their inhibitory activity on the nuclear translocation of NFATc1 in EGFP-NFATc1 U2OS cells. Among them, 6-[10'(Z)-heptadecenyl] salicylic acid (8) exhibited a significant inhibitory activity. In RAW 264.7 cells, it could dose-dependently prevent nuclear NFATc1 translocation induced by receptor activator of nuclear factor κB ligand (RANKL). The differentiation of osteoclasts from bone marrow derived macrophages (BMMs) was significantly inhibited by 8 in a dose-dependent manner. The mRNA expression of TRAP, CtsK, and MMP9, key enzymes for the bone resorption secreted by osteoclasts, were also significantly down-regulated; and MMP9 activity was also obviously decreased. More importantly, the bone resorption activity of osteoclasts was dose-dependently suppressed by compound 8. Our results suggest that compound 8 can effectively inhibit osteoclastogenesis and bone erosion via preventing NFATc1 nuclear translocation and might be a promising drug candidate for relevant diseases.
Assuntos
Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Salicilatos/farmacologia , Syzygium/química , Fosfatase Ácida/genética , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Reabsorção Óssea/genética , Catepsina K/genética , Linhagem Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Isoenzimas/genética , Macrófagos/efeitos dos fármacos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Medicina Tradicional Chinesa , Camundongos Endogâmicos BALB C , Estrutura Molecular , Osteoclastos/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/química , Ligante RANK/metabolismo , Ligante RANK/farmacologia , Salicilatos/isolamento & purificação , Fosfatase Ácida Resistente a TartaratoRESUMO
Five new polyhydroxypregnane glycosides, namely cynanotosides A-E (1-5), together with two known analogues, deacetylmetaplexigenin (6) and cynotophylloside H (7), were isolated from the roots of Cynanchum otophyllum. Their structures were established by spectroscopic methods and acid hydrolysis. The neuroprotective effects of compounds 1-7 against glutamate-, hydrogen peroxide-, and homocysteic acid (HCA)-induced cell death were tested by MTT assay in a hippocampal neuronal cell line HT22. Compounds 1, 2, and 7 exhibited protective activity against HCA-induced cell death in a dose-dependent manner ranging from 1 to 30µM, which may explain the Traditional Chinese Medicine (TCM) use of this plant for the treatment of epilepsy.
