ABSTRACT
One of the main goals of dentistry is the natural preservation of the tooth structure following damage. This is particularly implicated in deep dental cavities affecting dentin and pulp, where odontoblast survival is jeopardized. This activates pulp stem cells and differentiation of new odontoblast-like cells, accompanied by increased Wnt signaling. Our group has shown that delivery of small molecule inhibitors of GSK3 stimulates Wnt/ß-catenin signaling in the tooth cavity with pulp exposure and results in effective promotion of dentin repair. Small molecules are a good therapeutic option due to their ability to pass across cell membranes and reach target. Here, we investigate a range of non-GSK3 target small molecules that are currently used for treatment of various medical conditions based on other kinase inhibitory properties. We analyzed the ability of these drugs to stimulate Wnt signaling activity by off-target inhibition of GSK3. Our results show that a c-Met inhibitor, has the ability to stimulate Wnt/ß-catenin pathway in dental pulp cells in vitro at low concentrations. This work is an example of drug repurposing for dentistry and suggests a candidate drug to be tested in vivo for natural dentin repair. This approach bypasses the high level of economical and time investment that are usually required in novel drug discoveries.
Subject(s)
Cell Proliferation/drug effects , Dentin/cytology , Drug Repositioning , Odontoblasts/cytology , Pyrrolidinones/pharmacology , Quinolines/pharmacology , Small Molecule Libraries/pharmacology , Wnt Signaling Pathway/drug effects , Cells, Cultured , Dentin/drug effects , Dentin/metabolism , Humans , Odontoblasts/drug effects , Odontoblasts/metabolismABSTRACT
The purpose of this study was to investigate the crude extract of Serjania erecta Radlk., Sapindaceae, and its bioactive agents as preventive or inhibitor of memory loss in rodents, as well as other factors correlated with Alzheimer's syndrome: antioxidant and anticholinesterase activity, mainly as plant adaptogen - low toxicity and regulation action. The blocking cholinergic reversion activity (scopolamine) in the test of the passive avoidance was detected by measuring latency in young and adult animals. It presented low toxicity, with protective effect as shown by biochemical analysis (hypoglycemic/hypotriglyceridemic). Elevated levels (above 83 percent) of antioxidant activity were detected. AchE and BuChE inhibition were also detected in the chromatographic fractions, which were active both orally and directly on CNS (ICV).
O objetivo deste estudo foi pesquisar o extrato bruto de Serjania erecta Radlk., Sapindaceae, e seus bioativos como preventivos ou inibidores de perda de memória em roedores, e outros fatores correlacionados com a síndrome de Alzheimer: atividade antioxidante e anticolinesterásicas, principalmente como planta adaptógena, baixa toxicidade e ação regulatória. A reversão do bloqueador colinérgico (escopolamina) no teste da esquiva passiva foi detectada pela latência mensurada em animais jovens e adultos. Apresentou baixa toxicidade, com efeito protetor na análise bioquímica (hipoglicemia/hipotrigliceridemia). Índices elevados (acima 83 por cento) na atividade antioxidante foram observados. A inibição da AChE e BuChE foi perceptível nas frações cromatográficas, confirmando as ações via oral e diretamente no SNC.
